@article {pmid40449641,
year = {2025},
author = {Ruangjaroon, T and Paricharttanakul, NM and Chokchaichamnankit, D and Srisomsap, C and Lirdprapamongkol, K and Svasti, J},
title = {Toxicoproteomic study of fipronil in SH-SY5Y cells reveals induction of endoplasmic reticulum stress and necrotic cell death as neurodegenerative mechanisms.},
journal = {Toxicology in vitro : an international journal published in association with BIBRA},
volume = {},
number = {},
pages = {106098},
doi = {10.1016/j.tiv.2025.106098},
pmid = {40449641},
issn = {1879-3177},
abstract = {Exposure to pesticides has been considered as a risk factor for developing neurodegenerative diseases. The increasing use of fipronil, a phenylpyrazole insecticide, poses a risk to human health. This study aims to use toxicoproteomics for exploring neurodegenerative mechanism of fipronil in SH-SY5Y human neuroblastoma cells. In this study, fipronil at sub-cytotoxic and cytotoxic concentrations (43 and 78 μM) caused increases in superoxide level from 3 to 48 h after treatment, while intracellular glutathione level was decreased at 48 h. Neurite outgrowth of the cells was impaired by fipronil at both concentrations, while significant increase of cell death via apoptosis and necrosis modes were observed with fipronil at cytotoxic concentration. Pretreatment with antioxidant N-acetylcysteine (NAC) effectively relieved impairment of neurite outgrowth and induction of cell death by fipronil. Proteomic analysis showed that expression of proteins involving endoplasmic reticulum (ER) stress and unfolded protein responses were predominantly affected by fipronil. Immunoblotting confirmed the increased expression of ER stress markers, GRP78/BiP (78 kDa glucose-regulated protein/Binding immunoglobulin protein) and PDI (protein disulfide isomerase), in fipronil-treated cells. Improved understanding of the neurotoxic mechanism of fipronil may help in developing a strategy for reducing risk of neurodegenerative development from intense and prolonged use of fipronil.},
}

@article {pmid40446373,
year = {2025},
author = {Fang, X and Pan, B and Xie, Y and Shao, W and Li, J and Han, D and Hong, X and Tu, W and Zhao, Y and Wu, J and Zhu, Y and Zhang, Y and Li, W and Xu, Y and Kan, H and Chen, R},
title = {Mechanistic insights into ozone-induced asthma exacerbation: role of oxidative stress and IL-33.},
journal = {Journal of hazardous materials},
volume = {494},
number = {},
pages = {138760},
doi = {10.1016/j.jhazmat.2025.138760},
pmid = {40446373},
issn = {1873-3336},
abstract = {Short-term exposure to ozone is linked to the onset and exacerbation of asthma, yet the underlying mechanisms remain unclear. This study aims to elucidate the molecular pathways and key mediators involved in ozone-induced asthma exacerbation. In a longitudinal epidemiological study, each 10 µg/m[3] increase in ozone is associated with decreases in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) of 26.24 ml (95 % confidence interval [CI]: 11.16 ml, 41.33 ml), 19.10 ml (95 % CI: 6.96 ml, 31.24 ml), and 41.65 ml/s (95 % CI: 3.87 ml/s, 79.43 ml/s), respectively. In asthmatic mice, ozone exposure induces oxidative stress and worsens pulmonary dysfunction, lung tissue damage, and inflammation, disrupting the balance of type 2 innate lymphoid cells (ILC2s), T helper type 2 (Th2), and T helper type 17 (Th17) cells. These effects are partially mitigated by N-acetylcysteine (NAC). Furthermore, ozone exposure significantly increases the interleukin (IL)-33 level, while treatment with an IL-33 neutralizing antibody markedly improves lung dysfunction, inflammatory cell infiltration, and immune response dysregulation. In conclusion, this study highlights that short-term exposure to ozone has deleterious effects on asthmatic patients and animals by inducing oxidative stress in lungs and disrupting immune function via IL-33.},
}

@article {pmid40443238,
year = {2025},
author = {Elangovan, A and Singh, A and Iyer, M and Kumar, SM and Kinoshita, M and Krishnan, J and Parkash, J and Verma, N and Yadav, MK and Wander, A and Reddy, DH and Vellingiri, B},
title = {Unravelling the Mechanistic Approach of Aflatoxin Contaminated Food on Neurodegenerative Diseases-A Novel Approach.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.4817},
pmid = {40443238},
issn = {1099-1263},
abstract = {Aflatoxins (AFs) are a group of toxic secondary metabolites and a dietary toxin produced predominantly by Aspergillus species such as Aspergillus flavus and Aspergillus parasiticus. The four most common and harmful forms of AFs include Aflatoxin B1 (AFB1), Aflatoxin B2 (AFB2), Aflatoxin G1 (AFG1), and Aflatoxin G2 (AFG2), which pose a significant health threat due to their widespread contamination of food and feed products. Particularly, AFB1 has raised a major global health concern. Noxious neurological outcomes have been associated with chronic exposure to AF-contaminated food, contributing to development of neuropathies, demyelinating diseases, and cognitive decline. Disrupted tight junctions of blood-brain barrier (BBB) said to have implicated by AFs toxicity by directly damaging brain endothelial cells. Compromised BBB leads to the formation of DNA adducts, mitochondrial dysfunction, and impaired oxidative phosphorylation, contributing to oxidative stress in neuronal cells. AFs disrupt neuronal signaling pathways by generating reactive oxygen species (ROS) and initiating chronic inflammation, impairing cognitive function and motor control. Mounting evidences suggests that these factors trigger neurological disorders especially neurodegenerative disorders. Neuroprotective compounds, such as hesperetin, N-acetylcysteine (NAC), curcumin, and artichoke extract, have shown promise in counteracting AF-induced neurotoxicity. These compounds could reduce oxidative stress, attenuate inflammation, and support mitochondrial function, offering potential therapeutic strategies to mitigate AF-induced neurodegeneration. This review focuses on the molecular pathways through which AFs exert neurotoxic effects, highlighting their role in the onset of neurodegenerative diseases and potential neuroprotective compounds for therapies have been highlighted.},
}

@article {pmid40438181,
year = {2025},
author = {Liu, Y and Zhao, W and Huang, Q and Wan, L and Ren, Z and Zhang, B and Han, C and Yang, J and Zhang, H and Zhang, J},
title = {Advances in Research on the Release of von Willebrand Factor from Endothelial Cells through the Membrane Attack Complex C5b-9 in Sepsis.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {6719-6733},
pmid = {40438181},
issn = {1178-7031},
abstract = {Sepsis, a lethal organ dysfunction syndrome driven by aberrant host responses to infection, intertwines excessive inflammatory responses and dysregulated coagulation processes in its pathophysiology. Emerging research reveals the complement terminal membrane attack complex C5b-9 orchestrates ultralarge von Willebrand factor (ULVWF) release from vascular endothelial cells (ECs) through multifaceted mechanisms: C5b-9 compromises EC membrane integrity, activates calcium influx cascades, and provokes NLRP3 inflammasome signaling, triggering massive exocytosis of ULVWF stored within Weibel-Palade bodies (WPBs). When ADAMTS13 activity falters, undegraded ULVWF complexes with platelets to spawn microthrombi, precipitating microvascular occlusion and multiorgan collapse. Strikingly, elevated plasma von Willebrand factor (vWF) antigen levels in sepsis patients correlate robustly with endothelial injury, thrombocytopenia, and mortality-underscoring C5b-9-driven vWF release as a linchpin of septic coagulopathy. Current therapeutic strategies targeting these pathways, including recombinant ADAMTS13 (rhADAMTS13), N-acetylcysteine (NAC), and complement inhibitors like eculizumab, face limitations in clinical translation, necessitating further validation of their efficacy. Additionally, investigating complement regulatory molecules such as CD59 may unlock novel therapeutic avenues. Deciphering the intricate interplay within the C5b-9-vWF axis and advancing precision therapies hold transformative potential for ameliorating sepsis outcomes.},
}

@article {pmid40436274,
year = {2025},
author = {Marqués, J and Fernández-Irigoyen, J and Martínez-Azcona, M and Ainzúa, E and Marqués, V and Roncal, C and Orbe, J and Santamaría, E and Zalba, G},
title = {Endothelial NADPH oxidase 5 overexpression promotes thrombosis and alters thrombus composition by sex-dependent mechanisms in mice.},
journal = {Journal of thrombosis and haemostasis : JTH},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtha.2025.05.015},
pmid = {40436274},
issn = {1538-7836},
abstract = {BACKGROUND: Different members of the NADPH oxidases family (NOXs) participate in thrombosis. Nevertheless, the information about NOX5 in this process is scarce. The aim of this study was to test whether chronic expression of NOX5 may modulate thrombosis.

METHODS: To test this hypothesis, mice expressing human NOX5 at the endothelium and their control littermates underwent a FeCl3-induced thrombosis model in the carotid artery. The composition of the thrombi obtained from these mice was analysed by proteomics. The derived findings were corroborated by molecular analysis in vivo, in vitro and ex vivo. Finally, the antithrombic effects of N-acetylcysteine (NAC) and the pan-NOX inhibitor ML090 were tested.

RESULTS: The results from the present assay indicate that endothelial NOX5 expression promotes thrombosis in vivo in a sex-dependent manner. In female mice, NOX5 enhances prostaglandin E2 (PGE2) secretion and alters the expression of endothelial adhesion molecules. In male mice, NOX5 partially promotes the activation of circulating neutrophils. Both, NAC and ML090 protect against thrombosis in vivo.

CONCLUSIONS: In conclusion, our findings demonstrate that endothelial NOX5 plays a role in thrombosis, indicating that this oxidase should be considered as a therapeutic target to prevent thrombosis.},
}

@article {pmid40403956,
year = {2025},
author = {Hu, LJ and Li, CY and Xing, T and Wang, Y and Jiang, Q and Jiang, H and Wang, J and Tang, FF and Chang, YJ and Zhang, XH and Kong, Y and Huang, XJ},
title = {N-acetyl-L-cysteine promoted hematopoietic recovery in patients with acute myeloid leukemia after complete remission--A pilot study.},
journal = {Cancer letters},
volume = {625},
number = {},
pages = {217812},
doi = {10.1016/j.canlet.2025.217812},
pmid = {40403956},
issn = {1872-7980},
mesh = {Humans ; Pilot Projects ; *Leukemia, Myeloid, Acute/drug therapy/blood/pathology ; *Acetylcysteine/therapeutic use/administration & dosage/adverse effects ; Male ; Female ; Middle Aged ; Remission Induction ; *Hematopoiesis/drug effects ; Aged ; Adult ; Reactive Oxygen Species/metabolism ; Young Adult ; Treatment Outcome ; },
abstract = {Chemotherapy is a cornerstone treatment for acute leukemia (AL), but it often results in bone marrow (BM) failure, leading to infections, anemia, and bleeding, which significantly impact patient survival. Endothelial progenitor cells (EPCs) are critical elements of the BM microenvironment and are essential for hematopoiesis. Our previous research using in vitro and AML mouse models indicated that BM EPC dysfunction, characterized by impaired angiogenesis and elevated reactive oxygen species (ROS) levels in AML patients, could be partially reversed after complete remission (CR) and further improved with N-acetyl-L-cysteine (NAC) treatment. This pilot cohort study (NCT06024031, www.clinicaltrials.gov) evaluated the effects of NAC on hematopoietic recovery in 30 newly diagnosed AML patients after induction chemotherapy, compared to a propensity-matched control group of 60 patients. Patients received oral NAC (400 mg, three times daily) for 28 days post-chemotherapy alongside standard supportive care. NAC treatment did not affect CR rates (90 % vs. 80 %, P = 0.23), but significantly shortened platelet recovery time (19 vs. 22 days, P = 0.0001) among CR patients. NAC improved EPC percentages, reduced ROS, and enhanced EPC hematopoiesis-supporting functions in patients who achieved CR. NAC was safe and effective in promoting normal hematopoiesis recovery in AML patients in CR following chemotherapy.},
}

Humans
Pilot Projects
*Leukemia, Myeloid, Acute/drug therapy/blood/pathology
*Acetylcysteine/therapeutic use/administration & dosage/adverse effects
Male
Female
Middle Aged
Remission Induction
*Hematopoiesis/drug effects
Aged
Adult
Reactive Oxygen Species/metabolism
Young Adult
Treatment Outcome

@article {pmid40432447,
year = {2025},
author = {Máchalová, A and Landa, L and Máchal, J and Demlová, R and Slíva, J},
title = {The Effect of N-Acetylcysteine on Behavioral Sensitization to Methamphetamine in Mice.},
journal = {Physiological research},
volume = {74},
number = {2},
pages = {337-346},
pmid = {40432447},
issn = {1802-9973},
mesh = {Animals ; *Acetylcysteine/pharmacology/administration & dosage ; *Methamphetamine/pharmacology/administration & dosage ; Mice ; Male ; *Central Nervous System Stimulants/pharmacology ; *Behavior, Animal/drug effects ; },
abstract = {Behavioral sensitization is a phenomenon occurring after repeated administration of various psychotropic substances and it is characterized by gradually increasing response to the particular drug. It has been described for majority of addictive substances including amphetamines. It is considered to reinstate drug-seeking behaviour and plays important role in the processes associated with drug abuse and addiction. There are published reports, particularly on preclinical level, that N-acetylcysteine (NAC) may affect addictive properties of different classes of drugs (e.g., cocaine, heroin, alcohol, cannabinoids, nicotine). Since the lack of information on possible effects of NAC on amphetamine derivatives we decided to test possible influence of this substance on behavioral sensitization to methamphetamine (MET) in the mouse open field test. Our results have shown a decreased acute stimulatory effect of MET caused by NAC and moreover, there was a non-significant trend of attenuated development of behavioral sensitization to MET after simultaneous long-term administration of MET and NAC. This suppression of MET stimulatory effects therefore suggested on the preclinical level possible promising efficacy of NAC on addictive properties associated with MET similarly as it was demonstrated by other authors in association with cocaine or heroin. Key words: N-acetylcysteine, Methamphetamine, Behavioral sensitization.},
}

Animals
*Acetylcysteine/pharmacology/administration & dosage
*Methamphetamine/pharmacology/administration & dosage
Mice
Male
*Central Nervous System Stimulants/pharmacology
*Behavior, Animal/drug effects

@article {pmid40430469,
year = {2025},
author = {Zakaria, AY and Badawi, R and Osama, H and Abdelrahman, MA and El-Kalaawy, AM},
title = {A Comparative Study of N-Acetyl Cysteine, Rosuvastatin, and Vitamin E in the Management of Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Trial.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {5},
pages = {},
pmid = {40430469},
issn = {1424-8247},
abstract = {Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, randomized, controlled study was conducted and registered on clinicaltrials.gov (Identifier: NCT06105060), involving 135 NASH participants, who were divided into three groups: the control group (group 1), consisting of patients receiving standard therapy VE at a dosage of 400 IU twice daily. In the treated group (group 2), patients were administered NAC at a dosage of 1200 mg twice daily, while treatment (group 3) received RSV at a dosage of 20 mg once daily. FibroScan[®] examination of liver tissue and fibrosis scores, along with tests for liver aminotransferases, lipid profile, glycemic parameters, and renal and hepatic functions, were assessed before and after six months of treatment. Results: The analyzed groups demonstrated a significant reduction in steatosis and lipid peroxidation (p < 0.05). The NAC group demonstrated greater anti-inflammatory and anti-apoptotic effects compared to the RSV group, although this difference was not significant in the control group. NAC is conceded as the only significant antifibrotic agent in liver stiffness measurement (LSM), biological marker findings, and non-invasive liver fibrosis scores (p < 0.05), in addition to its improvement of several metabolic parameters and health-related quality of life. Conclusions: Patients receiving NAC demonstrated safety and efficacy in enhancing steatosis, fibrosis, and metabolic parameters, representing a novel strategy in the management of NASH.},
}

@article {pmid40429784,
year = {2025},
author = {Recinella, L and Pinti, M and Di Lodovico, S and Brenciani, A and Giovanetti, E and Diban, F and Di Giulio, M and Brunetti, L and Leone, S},
title = {A New Bromelain-Based Polyenzymatic Complex Plus N-Acetylcysteine: A Promising Approach for the Treatment of Urinary Tract Infections.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429784},
issn = {1422-0067},
support = {Difass International Spa 2024//Difass International Spa/ ; },
mesh = {Biofilms/drug effects ; *Urinary Tract Infections/drug therapy/microbiology ; Ciprofloxacin/pharmacology ; Animals ; Microbial Sensitivity Tests ; Escherichia coli/drug effects ; *Anti-Bacterial Agents/pharmacology/chemistry ; *Acetylcysteine/pharmacology/chemistry ; *Bromelains/chemistry/pharmacology ; Moths/microbiology ; Humans ; },
abstract = {Biofilm plays a crucial role in the pathogenesis and chronicity of urinary tract infections (UTIs). The present work aimed to evaluate the anti-biofilm effects of Formulation (DIF17BRO[®] plus NAC) in combination with ciprofloxacin (CPX) on Escherichia coli strains. The antimicrobial activity of ciprofloxacin was evaluated by minimum inhibitory concentration (MIC) determination, and the antibiofilm effects of ciprofloxacin alone and combined with Formulation were evaluated on E. coli ATCC700926, E. coli ATCC10536, E. coli PNT, and E. coli PCA mature biofilms in terms of CFU/mL and biomass quantifications. Moreover, the potential protective effects of Formulation plus ciprofloxacin was tested in a Galleria mellonella in vivo infection assay. Our results underlined the increased microbial reduction in the mature biofilm in the presence of the combination Formulation and CPX, even at a lower concentration of CPX. Formulation increased the percentage of biofilm biomass reduction, inducing a disruption of the biofilm structure itself. Our present findings confirm that MIC CPX combined with Formulation also induced an antimicrobial effect in the G. mellonella assay. Formulation facilitated the perturbation of the biofilm polymeric matrix, enhancing the antibiotic penetration and its antimicrobial action on bacteria, underlining Formulation's role as an enhancer of ciprofloxacin antibacterial action.},
}

Biofilms/drug effects
*Urinary Tract Infections/drug therapy/microbiology
Ciprofloxacin/pharmacology
Animals
Microbial Sensitivity Tests
Escherichia coli/drug effects
*Anti-Bacterial Agents/pharmacology/chemistry
*Acetylcysteine/pharmacology/chemistry
*Bromelains/chemistry/pharmacology
Moths/microbiology
Humans

@article {pmid40427046,
year = {2025},
author = {Hwang, I and Kang, CG and Lim, SJ and Kim, HJ and Kang, R and Jeon, SH and Lee, SH and Kim, JW and Kang, JS},
title = {Human Placenta Hydrolysate Protects Against Acetaminophen-Induced Liver Injury in Mice.},
journal = {Biomedicines},
volume = {13},
number = {5},
pages = {},
pmid = {40427046},
issn = {2227-9059},
support = {N/A//Green Cross Wellbeing/ ; },
abstract = {Background/Objectives: Acetaminophen (APAP) is a widely used analgesic and antipyretic, but overdose can lead to APAP-induced liver injury (AILI), a major cause of acute liver failure. While N-acetylcysteine (NAC) is the current standard of care, its efficacy is significantly reduced when administered after the peak time of liver injury, highlighting the need for alternative therapeutic strategies. Human placenta hydrolysate (HPH) has shown potential as a therapeutic agent for various liver diseases due to its rich content of bioactive compounds. This study aimed to investigate the hepatoprotective effects of HPH in a mouse model of AILI. Methods: HPH was administered to mice for three days prior to APAP treatment. The effects of HPH on liver morphology, necrosis, liver enzymes, phase I/II detoxification enzymes, oxidative stress markers, and inflammatory cytokines were evaluated. Results: HPH pretreatment attenuated APAP-induced liver necrosis and congestion, reduced serum levels of liver enzymes. In addition, HPH showed a concentration-dependent attenuation of APAP-induced decrease in human hepatocyte viability. HPH modulated phase I/II enzyme expression by downregulating CYP2E1 and upregulating SULT1A1, UGT1A6, GSTP1, and TPMT. HPH also exhibited antioxidant effects by increasing SOD and GPx activities, reducing MDA levels, and restoring the GSH/GSSG ratio. Furthermore, HPH attenuated the APAP-induced increase in the inflammatory cytokines TNF-α and IL-6. These findings suggest that HPH protects against AILI through multiple mechanisms, including the modulation of phase I/II detoxification, activation of antioxidants, and inhibition of inflammation. Conclusions: HPH could be a potential therapeutic option for APAP overdose and related liver injuries.},
}

@article {pmid40425069,
year = {2025},
author = {Morales, EN and Malecki, CC and Maruri, A and Sánchez, VR and Portu, A and Goldman, A and Chiaramoni, NS and Fenoy, IM},
title = {Preclinical evaluation of N-acetyl-cysteine in association with liposomes of lung surfactant's lipids for the treatment of pulmonary fibrosis and asthma.},
journal = {Toxicology and applied pharmacology},
volume = {},
number = {},
pages = {117412},
doi = {10.1016/j.taap.2025.117412},
pmid = {40425069},
issn = {1096-0333},
abstract = {PURPOSE: There is a need to generate new treatments against pulmonary diseases such as idiopathic fibrosis and asthma. N-acetylcysteine (NAC) has multiple clinical applications, but its unstable nature and route of administration limits its effectiveness. New pulmonary delivery strategies, such as liposomes made of lung surfactant lipids, could overcome NAC's limitations. This work aims to evaluate the efficacy of NAC combined with liposomes as a treatment for asthma and in preventing fibrotic development.

METHODS: Unilamellar vesicles were obtained through the dehydration-rehydration method followed by multiple membrane extrusion and characterized by Dynamic Light Scattering and Transmission electron microscopy. Lung fibrosis was induced by bleomycin administration, and liposomal formulation of NAC (LipoNAC) was evaluated as a preventive treatment. LipoNAC formulation was also evaluated in a therapeutic regimen for asthma using the classic ovalbumin model. For both models, the administration of the treatment was via the intranasal route.

RESULTS: NAC treatments (free NAC and LipoNAC) improved lung histopathology and decreased collagen deposition when tested in the lung fibrosis model. Only LipoNAC decreased serum levels of lactate dehydrogenase, myeloperoxidase activity in lung fluid and lung TGF-β. Although both treatments decreased Th2 cytokine and histopathological inflammation in the asthma model, only LipoNAC treatment significantly decreased mucus in asthmatic mice.

CONCLUSIONS: These results indicate that surfactant liposomal delivery of NAC potentiates its anti-inflammatory, mucolytic, and antioxidant activity, rendering it a promising therapy for respiratory diseases.},
}

@article {pmid40421021,
year = {2025},
author = {Rastgoo, S and Pourvali, K and Raeissadat, SA and Eslamian, G and Zand, H},
title = {Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1570441},
pmid = {40421021},
issn = {1664-3224},
mesh = {Humans ; *Acetylcysteine/administration & dosage ; Aged ; Male ; Female ; *Vitamin D/administration & dosage ; *Immunosenescence/drug effects ; *Vitamin D Deficiency/drug therapy/immunology/blood ; Leukocytes, Mononuclear/immunology/drug effects/metabolism ; Middle Aged ; Cellular Senescence/drug effects ; Dietary Supplements ; Aged, 80 and over ; },
abstract = {BACKGROUND: Immunosenescence is an important factor in the impaired immune response in older adults and plays a significant role in the development of biological aging. Targeting immunosenescence could present a novel pharmacological approach to mitigating aging and age-related diseases. We aimed to investigate the effect of N-acetylcysteine (NAC) and vitamin D (Vit-D) on the senescence of peripheral blood mononuclear cells (PBMCs).

METHOD: This randomized clinical trial was conducted on older adults with Vit-D deficiency. Eligible participants were randomly assigned to one of four groups to receive either (A) 1000 IU of Vit-D daily (D1) (B), 1000 IU of Vit-D plus 600 mg of NAC daily (D1N) (C), 5000 IU of Vit-D daily (D5), or (D) 5000 IU of Vit-D plus 600 mg of NAC daily (D5N) for 8 weeks. Senescence-associated beta-galactosidase (SA-β-gal) staining, expression of senescence-related genes, and serum inflammatory factors were measured at baseline and after 8 weeks.

RESULTS: After the intervention, supplementation with D5N and D5 significantly downregulated p16, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression and decreased SA-β-gal activity compared to the D1 group. Additionally, co-administration of NAC with 1000 IU of Vit-D significantly downregulated p16 transcripts in PBMCs compared to Vit-D 1000 IU alone. No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR) after the intervention.

CONCLUSIONS: The loading dose of Vit-D significantly attenuates senescence in PBMCs of older adults. However, co-administration of NAC with both the standard and loading doses of Vit-D further enhances these beneficial effects.

CLINICAL TRIAL REGISTRATION: https://irct.behdasht.gov.ir, identifier IRCT20230508058120N1.},
}

Humans
*Acetylcysteine/administration & dosage
Aged
Male
Female
*Vitamin D/administration & dosage
*Immunosenescence/drug effects
*Vitamin D Deficiency/drug therapy/immunology/blood
Leukocytes, Mononuclear/immunology/drug effects/metabolism
Middle Aged
Cellular Senescence/drug effects
Dietary Supplements
Aged, 80 and over

@article {pmid40420092,
year = {2025},
author = {Li, L and Lu, J and Fu, S and Li, W and Wang, Y and Wang, K and Tao, Y and Liu, S},
title = {Evodiamine induces ferroptosis in prostate cancer cells by inhibiting TRIM26-mediated stabilization of GPX4.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {71},
pmid = {40420092},
issn = {1749-8546},
support = {82203167//National Natural Science Foundation of China/ ; 82460722//National Natural Science Foundation of China/ ; GSWSQNPY2024-12//gansu provincial health industry science and technology innovation project/ ; CY2022-MS-A09//cuiying scientific and technological innovation program of lanzhou university second hospital/ ; CY2023-MS-A05//cuiying scientific and technological innovation program of lanzhou university second hospital/ ; GZKP2023-36//traditional chinese medicine scientific research project of gansu province, china/ ; CYXZ2024-11//cuiying scientific training program for undergraduates of lanzhou university/ ; },
abstract = {BACKGROUND: Prostate cancer is a major global health challenge, characterized by high morbidity and mortality rates. Traditional treatment options, including androgen deprivation therapy and chemotherapy, often lead to drug resistance. In recent years, natural compounds have garnered attention for their potential therapeutic effects. Evodiamine, a bioactive alkaloid from Evodia rutaecarpa, has demonstrated promising anti-cancer properties in various malignancies, including oral squamous cell carcinoma, breast, colorectal, and ovarian cancers. This study explores the efficacy of evodiamine in prostate cancer cells and investigates the mechanisms underlying evodiamine-induced cell death.

METHODS: To investigate the effects of evodiamine on prostate cancer cells, various cell lines, including both castration-sensitive and castration-resistant variants, were treated with different concentrations of evodiamine for various durations. Cell viability, proliferation, invasion ability, and colony formation were assessed using the CCK8 assay, EdU assay, 3D matrigel drop invasion assay, and colony formation assay, respectively. The effects of evodiamine on apoptosis were analyzed using FACS, Hoechst staining, and Western blot. To evaluate its effects on ferroptosis, malondialdehyde (MDA) and glutathione (GSH) assay kits, as well as DCFH-DA and the lipid peroxidation sensor BODIPY[™] 581/501 C11 fluorescent probes, were employed. The molecular mechanisms through which evodiamine regulates GPX4 protein instability were investigated using Western blot and TRIM26 ectopic expression. Additionally, a mouse xenograft model derived from DU145 cells was established to evaluate the in vivo effects of evodiamine and its molecular mechanisms, utilizing hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and Western blot analysis.

RESULTS: Evodiamine significantly suppressed cell viability, proliferation, invasion, and colony formation in prostate cancer cells. Importantly, evodiamine-induced cell death in the PC3 and DU145 cell lines was independent of apoptosis pathway. Instead, evodiamine increased reactive oxygen species (ROS) production, lipid ROS levels and MDA levels, while decreasing GSH levels, indicating the induction of ferroptosis. The key role of ROS in evodiamine-induced ferroptosis was further confirmed by the partial reversal of cell death upon treatment with the ROS scavenger N-acetylcysteine (NAC). Mechanistically, evodiamine induced ferroptosis by destabilizing GPX4 protein in a TRIM26-dependent manner. Moreover, in vivo studies demonstrated that evodiamine significantly inhibited tumor growth and induced ferroptosis in tumor cells, highlighting its therapeutic potential.

CONCLUSION: This study demonstrates that evodiamine exerts potent antitumor effects against prostate cancer through inhibiting TRIM26-mediated stabilization of GPX4 protein and triggering ferroptosis. These findings suggest that evodiamine, a natural product derived from traditional Chinese medicine, could be a promising therapeutic agent for prostate cancer.},
}

@article {pmid40418638,
year = {2025},
author = {Maxwell, MN and Murphy, BT and McDonald, FB and O'Halloran, KD},
title = {Exploring the respiratory efficacy of combined chronic glucocorticoid and antioxidant interventions in the mdx mouse: The PREDNAC trial.},
journal = {Experimental physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/EP092491},
pmid = {40418638},
issn = {1469-445X},
support = {SFI 19/FFP/6628 INSPIRE DMD/SFI_/Science Foundation Ireland/Ireland ; //Department of Physiology, UCC/ ; },
abstract = {Duchenne muscular dystrophy (DMD) is characterized by respiratory muscle injury and weakness, ultimately leading to respiratory failure. Impaired respiratory muscle performance, fibrosis and inflammation in early disease are evident in the dystrophin-deficient mdx mouse model of DMD. Prednisone or similar treatment is the current standard of care for DMD and exerts its benefits via an anti-inflammatory action, but chronic treatment is associated with side-effects. A recent study demonstrated improved function in mdx limb muscle with weekly glucocorticoid treatment compared with daily treatment. Herein, we investigated the effect of weekly α-methylprednisolone (PRED) treatment alone and the effect of PRED in combination with daily intake of the antioxidant N-acetyl cysteine, NAC (PREDNAC) on respiratory performance. One-month-old male mdx mice received PRED (0.8 mg/kg methylprednisolone i.p. weekly) or PREDNAC (0.8 mg/kg methylprednisolone i.p. weekly and 1% NAC in drinking water daily) for 3 months. At 4 months of age, conscious breathing was measured in vivo by whole-body plethysmography. Under urethane general anaesthesia, respiratory EMG and inspiratory pressure were measured at baseline and during maximal activity. The intrinsic force-generating capacity of the diaphragm was determined ex vivo. Neither PRED nor PREDNAC influenced breathing or diaphragm force-generating capacity in mdx mice. There was a significant increase in diaphragm and parasternal EMG activity, but inspiratory pressure was unchanged with treatment. We conclude that neither PRED nor PREDNAC has a major beneficial effect on respiratory system performance in the mdx mouse model of DMD. Weekly administration of glucocorticoids is inadequate to protect respiratory performance in mdx mice, which might reflect the higher duty cycle of respiratory muscles compared with limb muscles.},
}

@article {pmid40418545,
year = {2025},
author = {Varikasuvu, SR and Manne, M and Kumar, S and Mudgal, SK and Raj, V and Varshney, S and Gupta, P and Grover, A and Goyal, C and Lal, V and Singh, H and Lisa, M and Saransh Workshop Members, },
title = {COVID-19 clinical outcomes and N-acetylcysteine (CoViNAC study): a GRADE compliant meta-analysis of randomized controlled trials with molecular docking and dynamics simulation studies with Mpro of SARS-CoV-2.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {71},
number = {5},
pages = {95-102},
doi = {10.14715/cmb/2025.71.5.13},
pmid = {40418545},
issn = {1165-158X},
mesh = {Humans ; *Acetylcysteine/therapeutic use ; Molecular Docking Simulation ; *SARS-CoV-2/enzymology/drug effects ; Randomized Controlled Trials as Topic ; *Coronavirus 3C Proteases/metabolism/chemistry ; *COVID-19 Drug Treatment ; Molecular Dynamics Simulation ; COVID-19/mortality/virology ; Treatment Outcome ; Antiviral Agents/therapeutic use ; },
abstract = {N-acetylcysteine (NAC) has been proposed as an adjuvant therapy for COVID-19, but evidence from randomized controlled trials (RCTs) remains inconclusive. This systematic review and meta-analysis evaluated NAC's efficacy in improving mortality and recovery/discharge rates. Additionally, molecular docking and molecular dynamics simulation (MDMS) studies were conducted to assess NAC's interaction with the SARS-CoV-2 main protease (Mpro), a key enzyme for viral replication. A systematic search identified 12 RCTs, with 11 trials (1125 patients) included in the mortality analysis. NAC significantly reduced mortality (RR=0.59, 95% CI 0.39-0.88, p=0.01; I[2]=62%), indicating a 41% decreased risk of death. Six RCTs (656 patients) showed improved recovery/discharge rates (RR=1.09, 95% CI 1.03-1.14, p=0.003; I[2]=0%). MDMS studies demonstrated stable NAC binding at the Mpro catalytic site, interacting with His41 and Cys145, crucial for enzymatic activity. These findings suggest NAC significantly improves clinical outcomes in COVID-19 and may inhibit viral replication by targeting Mpro. This integrated evidence substantiates NAC's potential as a critical adjuvant therapy.},
}

Humans
*Acetylcysteine/therapeutic use
Molecular Docking Simulation
*SARS-CoV-2/enzymology/drug effects
Randomized Controlled Trials as Topic
*Coronavirus 3C Proteases/metabolism/chemistry
*COVID-19 Drug Treatment
Molecular Dynamics Simulation
COVID-19/mortality/virology
Treatment Outcome
Antiviral Agents/therapeutic use

@article {pmid40414419,
year = {2025},
author = {Chakraborty, S and Rao, S and Tripathi, SJ},
title = {The neuroprotective effects of N-acetylcysteine in psychiatric and neurodegenerative disorders: From modulation of glutamatergic transmission to restoration of synaptic plasticity.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110527},
doi = {10.1016/j.neuropharm.2025.110527},
pmid = {40414419},
issn = {1873-7064},
abstract = {N-acetylcysteine (NAC) is an effective pleiotropic drug with a strong safety profile. It is predominantly used as a mucolytic agent and in the treatment of paracetamol overdose. However, extensive research in the last decade has shown the prominent efficacy of NAC in many neuropsychiatric and neurodegenerative disorders. NAC acts through multiple mechanisms; primarily, it releases cysteine and modulates glutamatergic and monoaminergic transmission. Further, it restores glutathione levels, promotes oxidative balance, reverses decreased synaptic plasticity, reduces neuroinflammation and mitochondrial dysfunction, and provides neurotrophic support. Additionally, it regulates one-carbon metabolism pathways, leading to the production of key metabolites. In this review, we will be discussing in-depth mechanisms of action of NAC and its promising ability to reverse neuropathological changes, particularly cognitive deficits, and associated plasticity changes in various psychiatric and neurodegenerative diseases, including depression, bipolar disorders, schizophrenia, Alzheimer's disease, Huntington's disease, traumatic brain injury, aging. Overall, several preclinical studies and clinical trials have demonstrated the efficacy of NAC in reversing regressive plasticity, cognitive deficits, and associated changes in the brain. NAC remains among the strongest candidates with a high safety profile for managing several types of neurological disorders.},
}

@article {pmid40411876,
year = {2025},
author = {Chen, Y and Jiang, G and Huang, Y and Song, S and Fu, H and Du, B and Xiao, Y and Li, P and Shi, K and Huang, Y and Song, Q and Gao, X and Xie, Q},
title = {Lipoprotein-Based Nanocatalyst Enables Targeted Treatment of APAP-Induced Liver Injury via Enhanced Macropinocytosis.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e2500507},
doi = {10.1002/adhm.202500507},
pmid = {40411876},
issn = {2192-2659},
support = {82270618//National Natural Science Foundation of China/ ; 82070604//National Natural Science Foundation of China/ ; 82171358//National Natural Science Foundation of China/ ; 23S41900100//Shanghai Science and Technology Development Foundation/ ; 22QA1405000//Shanghai Rising-Star Program/ ; 2023ZKZD21//Shanghai Municipal Education Commission/ ; 2022YFC2502800//Key Technologies Research and Development Program/ ; 2018CR005//Ruijin Hospital/ ; shslczdzk01103//Shanghai Municipal Health Commission/ ; },
abstract = {Drug-induced liver injury (DILI), predominantly caused by acetaminophen (APAP) overdose, is characterized by excessive reactive oxygen species (ROS) production and subsequent hepatocyte necrosis. Although N-acetylcysteine (NAC) remains the only approved treatment, its effectiveness is limited by a narrow therapeutic time window and reduced efficacy in advanced cases. To address these limitations, an innovative therapeutic approach is developed utilizing ceria's antioxidant properties. In this study, a reconstituted high-density lipoprotein-encapsulated ceria nanocatalyst (CeO2-rHDL) is engineered to overcome the aggregation tendency and targeting limitation of naked ceria nanoparticles. These findings revealed that CeO2-rHDL enters hepatocytes through macropinocytosis, a process synergistically enhanced by both APAP and NAC, facilitating efficient liver targeting. The nanocatalyst demonstrated remarkable therapeutic efficacy by restoring mitochondrial function through ROS reduction. When combined with NAC, CeO2-rHDL significantly improved survival outcomes in DILI mice. This lipoprotein-based nanocatalyst system represents a promising therapeutic strategy for DILI treatment, offering enhanced targeting capabilities and improved therapeutic efficacy.},
}

@article {pmid40409732,
year = {2025},
author = {Kuttikrishnan, S and Suleman, M and Ahmad, F and Mariyam, Z and Habeeba, U and Prabhu, KS and Buddenkotte, J and Steinhoff, M and Uddin, S},
title = {Curcumin induces apoptosis via downregulation of SKP2 and induction of GADD45A/CDKN1A expression through generation of ROS in cutaneous T-cell lymphoma cells.},
journal = {Toxicology and applied pharmacology},
volume = {},
number = {},
pages = {117403},
doi = {10.1016/j.taap.2025.117403},
pmid = {40409732},
issn = {1096-0333},
abstract = {Curcumin, a plant derived natural product isolated from Curcuma longa. The aim of this study is to investigate the anti-proliferative effects and the underlying mechanisms of curcumin in Cutaneous T cell lymphoma (CTCL), a type of non-Hodgkin lymphoma that primarily affects the skin. The study found that curcumin induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and caspases leading to growth inhibition. Furthermore, Curcumin treatment downregulated the expression of S-phase kinase protein (SKP2) with concomitant upregulation of GADD45A, CDKN1A and CDKN1B. Curcumin also suppresses the expression of anti-apoptotic molecules including XIAP and cIAPs. Curcumin treatment of CTCL cells generates reactive oxygen species (ROS) and depletion of glutathione. Pretreatment of CTCL with N-acetyl cysteine prevented curcumin-mediated generation of ROS and prevention caspase activity. Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. Molecular docking studies revealed a strong binding affinity of curcumin to the active site of SKP2, primarily involving key residues crucial for its activity. Altogether, our results suggest that targeting SKP2 and GADD45A signaling by curcumin could be an attractive strategy for the treatment of CTCL.},
}

@article {pmid40409588,
year = {2025},
author = {Medisah, ME and Badiee, MS and Mahdavinia, M and Motamed, H and Rahmani, AH},
title = {Lactate is a prognostic marker of acute liver failure in early identification of patients susceptible to liver transplantation following acute acetaminophen poisoning.},
journal = {Annales pharmaceutiques francaises},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pharma.2025.05.007},
pmid = {40409588},
issn = {0003-4509},
abstract = {BACKGROUND: Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug, and its intentional or accidental overdose can lead to acute liver failure (ALF). Rapid prognosis and the selection of appropriate patients for transplantation in ALF are crucial. Lactate is the end product of anaerobic glycolysis and an indicator for determining the oxygen status in cells. The aim of this study was to investigate the relationship between serum lactate level and the prognosis of ALF due to acute APAP poisoning in patients referred to Razi Hospital, Ahvaz.

METHODS: This cross-sectional and prospective study was conducted on 34 healthy individuals (as controls) and 34 patients diagnosed with acute APAP poisoning. Serum levels of APAP, lactate, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T.bil), direct bilirubin (D.bil), and gamma-glutamyl transferase (GGT) were measured in healthy individuals and patients with acute APAP poisoning within 24 hours of admission. The relationship between the dose of APAP consumed, the amount of N-acetylcysteine (NAC) received, and the age and gender of the patients with lactate level was also evaluated.

RESULTS: The mean dose of APAP in the patients was 10.75 gr. A total of 85% of the patients received NAC. The mean volume of NAC injection was 4.4 mmol/L. The number of women with APAP overdose was higher than men. Lactate level increased with increasing APAP doses. The mean serum lactate level significantly reduced after 24 hours compared to the initial admission, and the levels of liver markers increased significantly after 24 hours.

CONCLUSION: In order to accept lactate as an international criterion in early identification of liver transplant candidate patients and reduce their mortality, clinical validity studies including definition and validation of clinical conditions related to lactate level and reliability tests are necessary. Therefore, early and periodic determination of serum lactate level seems to be essential as a promising biomarker for the prognosis of ALF caused by acute APAP poisoning.},
}

@article {pmid40404947,
year = {2025},
author = {Bai, H and Du, S and Qiu, D and Li, S and Gao, R and Zhang, Z},
title = {GPX4 Inhibition Contributes to NLRP3-Mediated Pyroptosis and Cognitive Impairment in Ketamine-Exposed Neonatal Rats.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40404947},
issn = {1559-1182},
support = {NDYB2022-4//Initial Scientific Research Foundation of Inner Mongolia Agricultural University/ ; NDYB2022-7//Initial Scientific Research Foundation of Inner Mongolia Agricultural University/ ; 31572580//National Natural Science Foundation of China/ ; 31572580//National Natural Science Foundation of China/ ; SYKJYB202301//Discipline Project of College of Veterinary Medicine/ ; },
abstract = {Increasing evidence reveals that multiple or prolonged exposure to ketamine causes hippocampal damage and cognitive dysfunction. However, the critical mechanisms underlying ketamine-induced neurotoxicity in the developing brain remain elusive. The present study was designed to investigate the role of GPX4 in ketamine-induced pyroptosis and cognitive dysfunction in the developing rat hippocampus. To achieve this goal, we conducted Western blotting, ELISA tests, histopathological analysis, Morris water maze tests, cell viability assays, and biochemical analyses on PC12 cells, HAPI cells, and 7-day-old rats. Additionally, N-acetylcysteine (NAC) and RSL3 were administered prior to continuous ketamine exposure. Our findings indicate that GPX4 inhibition by RSL3 enhances lipid peroxidation and mitochondrial damage, activates NLRP3/caspase-1 axis-dependent pyroptosis, and exacerbates hippocampal damage and cognitive dysfunction following ketamine exposure, while NAC effectively mitigates the effects of RSL3. Collectively, our in vivo and in vitro results support the notion that GPX4 may serve as a negative regulator of pyroptosis in ketamine-induced hippocampal damage and cognitive dysfunction. Our study proposes a novel strategy for treating ketamine-induced neurotoxicity through upregulating GPX4 expression.},
}

@article {pmid40401298,
year = {2024},
author = {Thomas, MC and Edwards, CJ and Dunlap, A},
title = {Practice Patterns for N-acetylcysteine Dosing for Acetaminophen Toxicity in the United States.},
journal = {Innovations in pharmacy},
volume = {15},
number = {4},
pages = {},
pmid = {40401298},
issn = {2155-0417},
abstract = {Background: Although the FDA approved acetaminophen toxicity dosing regimen for intravenous n-acetylcysteine (NAC) is a three-bag regimen, alternate regimens have been published which are generally simpler, and decrease errors and adverse effects. It is not clear how pervasive alternative regimens are used in hospitals in the US and reasons for a change from the FDA regimen. Objective: Characterize practice patterns for treating acetaminophen toxicity. Methods: A pilot-tested, electronic survey containing demographic and practice pattern questions for acetaminophen toxicity management was sent to residency program directors. The survey was open for 4 weeks with several reminder e-mails sent to non-responders. Descriptive statistics were used to summarize the data. Results: There were 119 responses (9.2% response rate). Responses were representative of all geographic areas in the US and were most commonly from community hospitals (67.2%) and those with 300 or more beds (72.2%). Nearly two-thirds used the FDA approved NAC regimen, whereas others used an alternate regimen. Reasons for making the change were for simplicity, to decrease errors or adverse events, or based on local poison center recommendations. More than one-third of respondents reported not using a maximum dosing weight. Conclusions: N-acetylcysteine is usually administered intravenously using the FDA approved regimen for acetaminophen toxicity. The weight for dosing was commonly capped at 100 kg, but some institutions did not use a maximum. Alternative intravenous regimens have been implemented at some institutions with the impetus for change being safety and simplicity.},
}

@article {pmid40400197,
year = {2025},
author = {Naseem, S and Xuan, MF and Hua, H and Park, S and Manzoor, A and Teng, H and Jin, H and Li, X and Li, Q},
title = {Vitamin C and N-acetylcysteine promotes bovine AD-MSCs proliferation and differentiation via Akt/mTOR/P70S6K signaling pathway for cultured meat production.},
journal = {Animal bioscience},
volume = {},
number = {},
pages = {},
doi = {10.5713/ab.24.0776},
pmid = {40400197},
issn = {2765-0189},
abstract = {OBJECTIVE: Traditional meat production is insufficient to meet the increasing protein requirements; necessitating cultured meat, which is safe, worthwhile, and scalable. Fat is crucial for making cultured meat more acceptable to consumers by enhancing flavour and providing a natural appearance. Mesenchymal stem cells from adipose tissue are a promising source for this purpose, but in vitro expansion of cells decreases their proliferation ability and increases cellular senescence. The objective of this study was to improve the proliferation and differentiation abilities of adipose-derived mesenchymal stem cells (AD-MSCs).

METHODS: In this study, vitamin C (VC) and N-acetylcysteine (NAC) antioxidants were used to treat AD-MSCs from Yanbian cattle testicles. CCK8, EdU staining, RT-qPCR, and western blot were used to test the cell viability and proliferation ability of AD-MSCs, ORO staining, triglycerides assay, and adipogenic specific markers expression were determined to analyse the adipogenic differentiation ability. Furthermore, oxidative stress parameters and activation of the Akt/mTOR/P70S6K signalling pathway were also studied.

RESULTS: Results showed that VC and NAC both increased proliferation and differentiation ability of AD-MSCs by increasing the expression of cell cycle regulatory and differentiation genes and proteins expression, and decreasing the expression of cell cycle inhibitory factors, and up-regulating stemness markers expression, while co-treatment showed enhanced effect. Oxidative stress was reduced by decreased ROS production, malondialdehyde content, and enhanced glutathione activity, as well as declined cellular senescence. Subsequently, the Akt/mTOR/P70S6K signalling pathway was activated by VC and VC+NAC treatment in AD-MSCs, while NAC only activates Akt expression, indicating its role in controlled cell growth.

CONCLUSION: This research concludes that NAC (2 mM) and VC (200 μM) improved the proliferation, differentiation potential, and stemness by decreasing oxidative stress and senescence, parallelly activating Akt/mTOR/P70S6K signalling pathway, while combined treatment (NAC+VC) enhanced these effects, providing bases for their utilisation to culture fat in cultivated meat production.},
}

@article {pmid40398509,
year = {2025},
author = {Chen, SJ and Wu, CL and Lin, LY and Horng, JL},
title = {Evaluating N-acetylcysteine for mitigating cisplatin-induced oxidative stress and ionocyte damage in a zebrafish model.},
journal = {Toxicology and applied pharmacology},
volume = {},
number = {},
pages = {117401},
doi = {10.1016/j.taap.2025.117401},
pmid = {40398509},
issn = {1096-0333},
abstract = {In this study, we examined the protective effects of N-acetylcysteine (NAC) against cisplatin-induced toxicity in zebrafish embryos. Cisplatin (cis-diamminedichloroplatinum II), a widely used anticancer drug, is associated with significant cytotoxic effects toward non-target tissues, including renal and ototoxic damage. Using zebrafish embryos exposed to cisplatin, we evaluated survival rates, hatching rates, ionocyte densities, oxidative stress, and platinum accumulation. NAC co-treatment significantly enhanced survival and hatching rates, preserved ionocyte density, mitigated oxidative stress, and reduced platinum accumulation. These findings highlight ionocytes as an effective model for assessing non-renal toxicity due to their high metabolic activity and mitochondrial abundance. The results suggest that NAC might serve as a co-therapeutic agent to alleviate cisplatin-induced toxicity during chemotherapy.},
}

@article {pmid40398422,
year = {2025},
author = {Sonar, SA and Bhat, R and Thompson, HL and Coplen, CP and Uhrlaub, JL and Jergovic, M and Nikolich, JŽ},
title = {Age-Related Oxidative Stress and Mitochondrial Dysfunction in Lymph Node Stromal Cells Limit the Peripheral T Cell Homeostatic Maintenance and Function.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70100},
doi = {10.1111/acel.70100},
pmid = {40398422},
issn = {1474-9726},
support = {P01 AG052359/AG/NIA NIH HHS/United States ; //Bowman Professorship in Medical Sciences/ ; },
abstract = {Lymph nodes (LN) are the key organs in charge of long-term maintenance of naïve lymphocytes and their initial, primary activation upon infection. Accumulating evidence indicates that LN stromal cells undergo degenerative changes with aging that critically impair LN function, including the generation of protective primary immune responses. The nature of these defects remains incompletely understood. We here demonstrate that age-related LN stromal changes manifest themselves in mitochondrial dysfunction and oxidative stress. Ex vivo, all three major stromal cell subsets, fibroblastic reticular cells (FRC), lymphatic endothelial cells (LEC), and blood endothelial cells (BEC) exhibit elevated mitochondrial reactive oxygen species (ROS) stress, reduced mitochondrial potential, and elevated mitochondrial mass with aging. Old FRC also exhibited elevated cytoplasmic ROS production. This was accompanied by the reduced ability of old LN stromal cells to support Tn survival in vitro, a defect alleviated by pretreating old LN stroma with the general antioxidant N-acetyl cysteine (NAC) as well as by mitochondrial ROS-reducing (mitoquinone) and mitophagy-inducing (urolithin A) compounds. Mitochondrial dysfunction and, in particular, reduced mitochondrial potential in old FRC were also seen upon vaccination or infection in vivo. Consistent with these results, in vivo antioxidant treatment of old mice with NAC restored to adult levels the numbers of antigen-specific CD8[+] effector T cells and their production of granzyme B in response to antigenic challenge.},
}

@article {pmid40397293,
year = {2025},
author = {Zheng, Y and Zou, X and Li, Q and Jiang, D and Zhu, F and Wu, Y},
title = {Exosomes derived from umbilical cord blood NK cells inhibit the progression of pancreatic cancer by targeting ROS-mediated mitochondrial dysfunction.},
journal = {Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society},
volume = {33},
number = {1-2},
pages = {8},
pmid = {40397293},
issn = {1319-0164},
support = {JYHL2022MS20//TaiShan Industrial Experts Programme/ ; 2023TSGC0549//Small and Medium Sized Enterprise Innovation Capability Enhancement Project of Shandong Province/ ; 2023ZDYF010144//Key Research and Development Program of Rizhao City/ ; JYSJ2022B04//the Practical Teaching Education Research Project Plan of Jining Medical University/ ; 202410443016//College Students' Innovative Entrepreneurial Training Plan Program/ ; },
abstract = {Emerging research indicates that natural killer (NK) cell-derived exosomes (NK-exo) play a significant role in cancer development. However, their regulatory mechanisms, particularly in pancreatic cancer, remain poorly elucidated. This study employed an in vitro co-culture system and an in vivo subcutaneous tumor model to evaluate the anti-tumor effect of NK-exo on pancreatic cancer. Umbilical cord blood (UCB)-derived NK-exo displayed characteristic exosomal morphology, size, and marker expression and was internalized by PANC- 1 cells. NK-exo significantly and dose-dependently reduce cell proliferation, migration, and invasion (P < 0.01). Further analysis demonstrated that NK-exo induced mitochondrial apoptosis in PANC- 1 cells by altering reactive oxygen species (ROS, P < 0.0001) and mitochondrial membrane potential (MPP) levels (P < 0.0001), effects that were significantly diminished with N-acetylcysteine (NAC) treatment (P < 0.0001). Furthermore, NK-exo treated PANC- 1 cells showed upregulation of the apoptotic markers Caspase3 (P < 0.0001) and Caspase9 (P = 0.0086) and reduced the release of PGC- 1α (P = 0.0064), TFAM (P < 0.0001), and SOD2 (P = 0.0021) as demonstrated by qRT-PCR. Western blot analyses revealed a dose dependent significant elevation of total Caspase3, Caspase9, Bax, and cytochrome c level and depression in the anti-apoptotic Bcl- 2. Animal experiments further confirmed that NK-exo treatment significantly reduced tumor volume and weight and increased Bax protein expression relative to the tumor model group. These findings indicate that NK-exo can enter PANC- 1 cells via endocytosis, induce mitochondrial oxidative damage, and suppress PANC- 1 cell progression, thereby demonstrating a robust anti-pancreatic cancer effect.},
}

@article {pmid40394754,
year = {2025},
author = {Sun, Y and Zhou, Y and Huang, D and Zhao, Z and Shao, Q and Li, J and Zhao, X and Liu, X},
title = {Erk1/2 Orchestrates SSPH I-Induced Oxidative Stress, Mitochondrial Dysfunction and Ferroptosis in Hepatocellular Carcinoma.},
journal = {Journal of cellular and molecular medicine},
volume = {29},
number = {10},
pages = {e70609},
pmid = {40394754},
issn = {1582-4934},
support = {82060793//National Natural Science Foundation of China/ ; 2021JJB140005//Natural Science Foundation of Guangxi Province/ ; 2022C043//Young talents in Gui Pai Xing lin of Guangxi University of Chinese Medicine/ ; 2021007//Qihuang Project Team of Guangxi University of Chinese Medicine/ ; },
mesh = {*Ferroptosis/drug effects ; *Carcinoma, Hepatocellular/metabolism/pathology/drug therapy ; Humans ; *Liver Neoplasms/metabolism/pathology/drug therapy ; *Oxidative Stress/drug effects ; Animals ; *Mitochondria/drug effects/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Mice ; *MAP Kinase Signaling System/drug effects ; *Saponins/pharmacology ; Cell Line, Tumor ; Mice, Nude ; Iron/metabolism ; Cell Survival/drug effects ; Xenograft Model Antitumor Assays ; Butadienes ; Nitriles ; },
abstract = {Although Erk1/2 has been linked to oxidative stress regulation in hepatocellular carcinoma (HCC), the interplay among Erk1/2, reactive oxygen species (ROS), and iron metabolism remains poorly characterised. The steroidal saponin SSPH I, a recognised ferroptosis inducer, exerts dual pharmacological effects via Erk1/2 and ROS-dependent pathways. This study aimed to investigate the regulatory mechanisms of Erk1/2 in ferroptosis and oxidative stress and analyse their feedback regulatory effects on Erk1/2 in HCC using SSPH I as a pharmacological probe, and further elucidate the anti-HCC effects and mechanisms of SSPH I in vitro and in vivo. Mechanistic studies utilised three inhibitors: U0126 (Erk1/2 phosphorylation inhibitor), Ferrostatin-1 (ferroptosis inhibitor), and N-acetyl cysteine (ROS scavenger), combined with SSPH I to delineate its effects on cell viability, mitochondrial dynamics, ferroptosis induction and oxidative stress. Mechanistically, SSPH I disrupted mitochondrial function and suppressed HCC cell survival through iron accumulation and ROS generation, while concurrently activating Erk1/2 signalling. Pharmacological inhibition of ROS or iron pathways partially attenuated SSPH I-induced ferroptosis and ROS generation, but failed to abrogate these effects. Erk1/2 inhibition completely abolished SSPH I-mediated regulation of the Nrf1/2-HO-1 axis and ferroptosis-related protein expression in cellular and animal models, identifying Erk1/2 as the upstream regulatory node. Notably, while both SSPH I and U0126 monotherapies inhibited xenograft growth, their combined use resulted in antagonistic effects. These findings establish Erk1/2 activation as the central molecular mechanism orchestrating SSPH I-driven oxidative stress amplification, mitochondrial dysfunction and ferroptosis execution in HCC.},
}

*Ferroptosis/drug effects
*Carcinoma, Hepatocellular/metabolism/pathology/drug therapy
Humans
*Liver Neoplasms/metabolism/pathology/drug therapy
*Oxidative Stress/drug effects
Animals
*Mitochondria/drug effects/metabolism/pathology
Reactive Oxygen Species/metabolism
Mice
*MAP Kinase Signaling System/drug effects
*Saponins/pharmacology
Cell Line, Tumor
Mice, Nude
Iron/metabolism
Cell Survival/drug effects
Xenograft Model Antitumor Assays
Butadienes
Nitriles

@article {pmid40395300,
year = {2023},
author = {Campos-Blázquez, JP and Flores-Maldonado, C and Gallardo, JM and Bonilla-Delgado, J and Pedraza-Ramírez, AA and López-Méndez, O and Cortés-Malagón, EM and Contreras, RG},
title = {Ouabain promotes claudin-1, -2, and -4 autophagic degradation through oxidative stress and AMPK activation in MDCK cells.},
journal = {Autophagy reports},
volume = {2},
number = {1},
pages = {2256146},
pmid = {40395300},
issn = {2769-4127},
abstract = {Epithelial cells transport substances through the cellular and paracellular pathways. The last one depends on tight junctions, particularly on claudins, the family of integral membrane proteins responsible for the permeability and selectivity of these junctions. 300 nM ouabain (OUA) induces endocytosis and lysosomal degradation of claudin-2 and -4 in an Src and ERK1/2 kinases-dependent manner. Here we investigate whether OUA-induced lysosomal degradation of claudins implicates autophagy in renal epithelial Madin-Darby canine kidney cells. During autophagy, LC3 protein binds phosphatidylethanolamine and incorporates, together with protein p62, into the phagophore. Subsequently, the autolysosome degrades both LC3 and p62 proteins. OUA's occupancy of its site in the Na[+]/K[+]ATPase (300 nM, 10 h) increases autophagic flux because of degradation of LC3 and p62 and an increase in the number of autophagosomes, as detected by fluorescent LC3 and p62 puncta and the rise in autolysosomes seen by the GFP-LC3-RFP probe. Finally, OUA increases the colocalisation of claudin-1, -2, or -4 with p62 in these puncta. OUA induces autophagy increasing reactive oxygen species generation that activates AMP-activated protein kinase, phosphorylating ULK1 at S555. The autophagy inducer rapamycin causes a degradation of the studied claudins comparable to the one generated by OUA. Furthermore, the autophagy inhibitor dorsomorphin blocks OUA-induced autophagy and claudin-1, -2, and -4 degradation. These results demonstrated that OUA induces claudin-1, -2, and -4 autophagy through oxidative stress. Abbreviations: AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATP: Adenosine triphosphate; DM: dorsomorphin; EGFR: epidermal growth factor receptor; ERK: extracellular signal-regulated kinase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; LC3: microtubule-associated protein 1A/1B-light chain 3; MDCK: Madin-Darby canine kidney; mTOR: mammalian target of rapamycin; NAC: N-acetylcysteine; OUA: ouabain; PCC: Pearson's correlation coefficient; PE: phosphatidylethanolamine, Rapa: rapamycin; ROS: reactive oxygen species; SNK: Student-Newman-Keuls; TER: transepithelial electrical resistance; TJs: tight junctions; ULK1: Unc-51-like kinase 1.},
}

@article {pmid40394693,
year = {2025},
author = {Chen, Y and Nan, Y and Xu, L and Dai, A and Orteg, RMM and Ma, M and Zeng, Y and Li, J},
title = {Polystyrene nanoplastics exposure induces cognitive impairment in mice via induction of oxidative stress and ERK/MAPK-mediated neuronal cuproptosis.},
journal = {Particle and fibre toxicology},
volume = {22},
number = {1},
pages = {13},
pmid = {40394693},
issn = {1743-8977},
support = {2022ZD0211600//Science and Technology Innovation 2030 Major Projects/ ; },
mesh = {Animals ; *Oxidative Stress/drug effects ; Male ; Mice, Inbred C57BL ; *Polystyrenes/toxicity ; *Copper/metabolism/toxicity ; *Neurons/drug effects/pathology ; *Cognitive Dysfunction/chemically induced ; MAP Kinase Signaling System/drug effects ; Humans ; Mice ; *Nanoparticles/toxicity ; *Microplastics/toxicity ; Cell Line, Tumor ; },
abstract = {BACKGROUND: Recent studies emphasize the significance of copper dyshomeostasis in neurodegenerative diseases, such as Alzheimer's and Parkinson's, thereby highlighting the role of copper in neurotoxicity. Cuproptosis, a novel mechanism of copper-dependent cell death, remains underexplored, particularly concerning environmental pollutants like polystyrene nanoplastics (PS-NPs). While PS-NPs are recognized for inducing neurotoxicity through various forms of cell death, including apoptosis and ferroptosis, their potential to trigger neuronal cuproptosis has not yet been investigated. This study aims to determine whether exposure to PS-NPs induces neurotoxicity via cuproptosis and to explore the preliminary molecular mechanisms involved, thereby addressing this significant knowledge gap.

METHODS: Seven-week-old male C57BL/6 mice were exposed to PS-NPs at dose of 12.5 mg/kg, and were co-treated with the antioxidant N-acetylcysteine (NAC). Complementary in vitro experiments were conducted using SH-SY5Y neuronal cells exposed to PS-NPs at a concentration of 0.75 mg/mL, with interventions that included the copper chelator tetrathiomolybdate (TTM), NAC, and the MAPK inhibitor PD98059.

RESULTS: Exposure to PS-NPs significantly increased cerebral copper accumulation (P < 0.05) and induced cuproptosis, characterized by lipid-acylated DLAT oligomerization, dysregulation of cuproptosis regulators (FDX1, LIAS, HSP70), and mitochondrial damage. In murine models, PS-NPs elicited neurotoxicity, as evidenced by neuronal loss, decreased Nissl body density, impaired synaptic plasticity, and suppressed oxidative stress markers (GSH, SOD, Nrf2), alongside activation of the ERK-MAPK pathway, ultimately resulting in deficits in learning and memory. Treatment with NAC alleviated these adverse effects. In SH-SY5Y cells, exposure to PS-NPs resulted in reduced cell viability (p < 0.01), an effect that was mitigated by TTM. Furthermore, NAC and PD98059 were found to reverse elevated copper levels, cuproptosis markers, and mitochondrial anomalies (p < 0.05).

CONCLUSION: This study presents preliminary evidence indicating that PS-NPs may induce neuronal cuproptosis, potentially through the oxidative stress-mediated activation of the ERK-MAPK pathway, which contributes to cognitive dysfunction in mice. These findings provide insights into the potential mechanisms underlying PS-NPs neurotoxicity and highlight possible therapeutic targets, such as copper chelation or MAPK inhibition, for mitigating the neurological risks associated with nanoplastic exposure, pending further validation in human-relevant models.},
}

Animals
*Oxidative Stress/drug effects
Male
Mice, Inbred C57BL
*Polystyrenes/toxicity
*Copper/metabolism/toxicity
*Neurons/drug effects/pathology
*Cognitive Dysfunction/chemically induced
MAP Kinase Signaling System/drug effects
Humans
Mice
*Nanoparticles/toxicity
*Microplastics/toxicity
Cell Line, Tumor

@article {pmid40389439,
year = {2025},
author = {Zhang, YH and Dai, CS and Wang, YJ and Wang, WY and Qi, TT and Xia, MC and Zhou, G and Cui, YM},
title = {Intestinal permeability of N-acetylcysteine is driven by gut microbiota-dependent cysteine palmitoylation.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4623},
pmid = {40389439},
issn = {2041-1723},
support = {82204515//National Natural Science Foundation of China (National Science Foundation of China)/ ; 7232262//Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)/ ; },
mesh = {*Gastrointestinal Microbiome/physiology ; *Acetylcysteine/metabolism/pharmacokinetics ; Animals ; Humans ; Rats ; Male ; Permeability ; *Cysteine/metabolism ; Lipoylation ; *Intestinal Mucosa/metabolism ; Rats, Sprague-Dawley ; Female ; Specific Pathogen-Free Organisms ; Germ-Free Life ; Intestinal Barrier Function ; },
abstract = {Trillions of intestinal microbiota are essential to the permeability of orally administered drugs. However, identifying microbial-drug interactions remains challenging due to the highly variable composition of intestinal flora among individuals. Using single-pass intestinal perfusion (SPIP) platform, we establish the microbiota-based permeability screening framework involving germ-free (GF) and specific-pathogen-free (SPF) rats to compare in-situ Peff-values and metabolomic profiles of 32 orally administered drugs with disputable classifications of permeability, prior to the verifications of bioorthogonal chemistry and LC-MS/MS. In contrast with SPF controls, N-Acetylcysteine (NAC) exhibits significantly increased permeability in GF rats, which is inversely related to reduced cysteine-3-ketosphinganine by Bacteroides. To further validate these microbiome features, we integrate clinical descriptors from a prospective cohort of 319 participants to optimize a 15-feature eXtreme Gradient Boosting (XGB) model, which reveal that cysteine palmitoylation by intestinal microbiota has significantly affected NAC permeability. By comparison of net reclassification improvement (NRI) index, this machine learning (ML) model of clinical prediction model encompassing intestinal microbial features outperforms other three commercial models in predicting NAC permeability. Here we have developed an intestinal microbiota-based strategy to evaluate uncharacterized NAC permeability, thus accounting for its discordant biopharmaceutics classification.},
}

*Gastrointestinal Microbiome/physiology
*Acetylcysteine/metabolism/pharmacokinetics
Animals
Humans
Rats
Male
Permeability
*Cysteine/metabolism
Lipoylation
*Intestinal Mucosa/metabolism
Rats, Sprague-Dawley
Female
Specific Pathogen-Free Organisms
Germ-Free Life
Intestinal Barrier Function

@article {pmid40387057,
year = {2025},
author = {Zhang, Y and Chen, M and Niu, R and Guo, D and Sun, Z},
title = {Mechanistic Insights into T-2 Toxin-Induced Thymic Epithelial Cell Injury and Immunotoxicity via the ROS-NF-κB-NLRP3 Signaling Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c00355},
pmid = {40387057},
issn = {1520-5118},
abstract = {Thymic epithelial cells (TECs) are critical for thymic structure and function, yet the impact of T-2 toxin (T-2) on TECs and related molecular pathways remains unclear. This study sheds light on the mechanisms of T-2-induced TEC damage, focusing on the ROS-NF-κB-NLRP3 signaling axis. The in vivo and in vitro analyses suggest that T-2 induces TEC injury through ROS-driven NLRP3 inflammasome activation, NF-κB signaling, inflammation, and apoptosis. Molecular docking analysis verified the binding of T-2 to critical components involved in oxidative stress, inflammatory signaling pathways, and apoptosis. These findings were further supported by therapeutic interventions targeting ROS and NLRP3. N-acetylcysteine (NAC) effectively reduced ROS levels, suppressed NF-κB signaling, inhibited NLRP3 activation, and mitigated inflammation and apoptosis, effects mirrored by the NLRP3 inhibitor MCC950, emphasizing the critical role of ROS-mediated NLRP3 inflammasome activation through NF-κB signaling in T-2-induced TEC damage. Concurrently, inhibition of the NF-κB signaling further suppressed ROS levels, NLRP3 inflammasome activation, and apoptosis in MTEC1 cells, emphasizing the pivotal function of the ROS-NF-κB-NLRP3 axis in the pathogenesis of T-2-induced thymic injury. Our study offers an in-depth insight into the mechanisms driving T-2-induced immunotoxicity and identifies potential therapeutic strategies targeting these pathways to mitigate thymic injury and preserve immune function.},
}

@article {pmid40384860,
year = {2025},
author = {Gallego-Rentero, M and Botella, LM and Mascaraque, M and Nicolás-Morala, J and Albiñana, V and Abarca-Lachen, E and Gilaberte, Y and González, S and Juarranz, Á and Carrasco, E},
title = {N-acetylcysteine and raloxifene boost photodynamic therapy against cutaneous squamous cell carcinoma by decreasing TGFβ1 secreted by cancer-associated fibroblasts.},
journal = {International journal of biological sciences},
volume = {21},
number = {7},
pages = {3164-3182},
pmid = {40384860},
issn = {1449-2288},
mesh = {*Photochemotherapy/methods ; *Raloxifene Hydrochloride/therapeutic use/pharmacology ; Animals ; *Carcinoma, Squamous Cell/drug therapy/metabolism ; *Acetylcysteine/therapeutic use/pharmacology ; Mice ; *Transforming Growth Factor beta1/metabolism ; *Skin Neoplasms/drug therapy/metabolism ; Humans ; Cell Line, Tumor ; *Cancer-Associated Fibroblasts/metabolism/drug effects ; },
abstract = {Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent skin cancer. While surgery remains the gold standard treatment, non-invasive methods like photodynamic therapy (PDT) stand out for their high efficacy and minimal cosmetic impact. However, resistance to PDT is still a challenge. Numerous cellular processes involved in cancer biology and therapy resistance are regulated by the TGFβ1/SMAD pathway. Using in vitro bidimensional and tridimensional cultures of cSCC cell lines, we studied the development of resistance to PDT in response to TGFβ1 secreted by cancer associated fibroblasts. Our results highlight the TGFβ1 co-receptor endoglin as a key molecular player in the process. Importantly, targeting endoglin expression with N-acetylcysteine (NAC) or raloxifene significantly reduced TGFβ1 levels and effectively prevented resistance. In addition, the combination of PDT with NAC resulted in an improved therapeutic outcome in vivo in SKH-1 mice with cSCC photogenerated by chronic exposition to ultraviolet light. In conclusion, the combination of PDT with NAC or raloxifene enhances PDT efficacy by mitigating resistance mechanisms, which can open new avenues for the treatment of cSCC.},
}

*Photochemotherapy/methods
*Raloxifene Hydrochloride/therapeutic use/pharmacology
Animals
*Carcinoma, Squamous Cell/drug therapy/metabolism
*Acetylcysteine/therapeutic use/pharmacology
Mice
*Transforming Growth Factor beta1/metabolism
*Skin Neoplasms/drug therapy/metabolism
Humans
Cell Line, Tumor
*Cancer-Associated Fibroblasts/metabolism/drug effects

@article {pmid40381462,
year = {2025},
author = {Liu, M and Ding, C and Yi, Q and Quan, H and Li, W and Wang, Y and Lin, X and Wang, M and Wang, J},
title = {Carboxylesterase-activated hepatocyte-targeting fluorescent probe for drug-induced liver injury diagnosis.},
journal = {Bioorganic chemistry},
volume = {162},
number = {},
pages = {108587},
doi = {10.1016/j.bioorg.2025.108587},
pmid = {40381462},
issn = {1090-2120},
abstract = {In this study, a novel fluorescent probe DCI-Gal-Bz toward CEs was developed. DCI-Gal-Bz exhibits excellent sensitivity and selectivity toward CEs, which is not disturbed by physiologically relevant interferences. DCI-Gal-Bz could specifically distinguish hepatocytes from A549, HeLa, and SGC-7901 cells, showing good hepatocyte-targeting potential, which is because the terminal galactose of DCI-Gal-Bz can be selectively recognized by HepG2 cells overexpressing ASGPR. DCI-Gal-Bz could effectively monitor CEs activity in APAP-induced liver injury (DILI), and reveal the upregulation of CEs during N-acetylcysteine (NAC) hepatoprotective therapy. In other words, DCI-Gal-Bz can clearly distinguish between healthy, injured and repaired states, being a powerful tool for exploring liver CEs-related diseases.},
}

@article {pmid40381010,
year = {2025},
author = {Li, J and Zheng, Q and Wang, F},
title = {Fabrication of N-acetylcysteine-loaded chitosan-cloaked polyphenol nanoparticles for treatment of pediatric pneumonia and acute lung injury.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {40381010},
issn = {1432-1912},
abstract = {Bacterial infectious acute pneumonia has long presented a significant barrier to human health and the fast elimination of antibacterial in lung tissue. Engineering nanoformulations that are easily prepared and possess mucoadhesive characteristics for administering antibacterial drugs are crucial for addressing pneumonia and lung injury. This investigation utilized FDA-approved tannic acid (TA) to develop a nanocomplex by cloaking chitosan (CH) to attain prolonged anti-infection efficacy against acute pneumonia. The flash nanocomplexation (FNC) process was employed for developing chitosan-cloaked poly(vinyl alcohol)/TA/N-acetylcysteine (NAC) nanoparticles (CPTN NPs) using NAC as the model drug, relying on non-covalent interactions between the components. The investigation of pneumonia revealed that the robust electrostatic interaction between negatively charged mucin and positively charged chitosan in the trachea facilitated the retention of NAC in the lungs for a minimum of 24 h post-inhalation of CPTN NPs, effectively constraining pneumonia within 3 days. The DPPH values of 97.42 ± 5.1 for CPTN NPs reveal excellent antioxidant ability. The cell viability of NCI-H441 and A549 cells remained above 90% of 100 μg/mL for NAC and CPTN NPs. The antibacterial efficacy of CPTN NPs exhibited a 99.9% reduction compared to the untreated group. The mucoadhesive CPTN NPs, characterized by excellent biocompatibility and produced using a simple and reproducible method, may offer a novel approach to administering CPTN NPs to address acute pediatric pneumonia and lung injury.},
}

@article {pmid40380998,
year = {2025},
author = {Sun, S and Wang, Y and Shen, Y and Li, W and Hu, Z and Peng, Y and Zheng, J},
title = {Metabolic activation and cytotoxicity of carvedilol mediated by cytochrome P450s in vitro and in vivo.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {40380998},
issn = {1432-0738},
abstract = {Carvedilol (CAR) is commonly administered in the treatment of essential hypertension. Current reports suggest that CAR therapy may elevate the risk of hepatotoxicity, occasionally progressing to liver injury. However, the underlying mechanisms of the toxicity remain poor understood. This study investigated CAR-associated hepatotoxicity through reactive metabolites formation. In the microsomal incubation mixture containing CAR (50 μM), four phase I metabolites (M1-M4) were detected. Upon the addition of glutathione (GSH), N-acetylcysteine (NAC), or cysteine as trapping agents, four GSH conjugates (M5-M8), four NAC conjugates (M9-M12), and four cysteine conjugates (M13-M16) were also detected. Chemical synthesis of 8-hydroxy CAR identified M1 as the primary oxidative metabolite of CAR. Following the administration of CAR (25 mg/kg), we detected GSH conjugate (M5) in bile, NAC conjugate (M9) in urine, and cysteine adduct (M13) in proteolytic mixture of liver tissues of rat. Furthermore, it was found that CYP3A4 dominated the metabolic activation of CAR. Additionally, CAR exhibited time-course changes and dose-dependent (0, 25, 50, and 100 mg/kg) protein adduction in rat liver tissues, as well as time- and concentration-dependent (0, 10, 25, 50 and 100 μM) inhibition of hepatocyte viability. Ketoconazole (KTZ) significantly decreased the susceptibility of hepatocytes to CAR-induced cytotoxicity. Collectively, these findings offer new insight into the hepatotoxicity mechanism associated with the metabolic activation of CAR.},
}

@article {pmid40375363,
year = {2025},
author = {Edzeamey, FJ and Ramchunder, Z and Valle Gómez, A and Ge, H and Marobbio, CMT and Pourzand, C and Virmouni, SA},
title = {Therapeutic combination of L-ascorbic acid, N-acetylcysteine, and dimethyl fumarate in Friedreich's ataxia: insights from in vitro models.},
journal = {Redox report : communications in free radical research},
volume = {30},
number = {1},
pages = {2505303},
pmid = {40375363},
issn = {1743-2928},
mesh = {*Acetylcysteine/pharmacology/therapeutic use ; *Dimethyl Fumarate/pharmacology/therapeutic use ; *Friedreich Ataxia/drug therapy/metabolism ; *Ascorbic Acid/pharmacology/therapeutic use ; Humans ; Reactive Oxygen Species/metabolism ; Mitochondria/drug effects/metabolism ; Fibroblasts/metabolism/drug effects ; Frataxin ; Oxidative Stress/drug effects ; Antioxidants/pharmacology/therapeutic use ; Membrane Potential, Mitochondrial/drug effects ; Iron-Binding Proteins/metabolism/genetics ; NF-E2-Related Factor 2/metabolism ; Cell Survival/drug effects ; },
abstract = {Friedreich's Ataxia (FRDA) is a rare neurological disorder caused by an abnormal expansion of Guanine-Adenine-Adenine (GAA) repeat in intron 1 of the FXN gene, which encodes frataxin, leading to reduced expression of frataxin, a mitochondrial protein essential for cellular homeostasis. Frataxin deficiency results in oxidative stress and mitochondrial dysfunction and impaired redox balance. Currently, there is no cure for FRDA. This study aimed to evaluate the therapeutic potential of antioxidants dimethyl fumarate (DMF), N-acetylcysteine (NAC), and L-ascorbic acid (LAA) in restoring mitochondrial redox homeostasis and frataxin levels in FRDA patient-derived fibroblasts and 2D sensory neurons. We assessed cell viability, mitochondrial and cellular reactive oxygen species (ROS) levels, mitochondrial DNA copy number, mitochondrial membrane potential, and frataxin and NRF2 expression at both mRNA and protein levels following antioxidant treatment, either individually or in combination. Treatment with LAA, NAC, and DMF resulted in significant reductions in mitochondrial and cellular ROS, along with increased FXN and NRF2 expression, and enhanced NRF2 nuclear translocation. Furthermore, these compounds improved aconitase/citrate synthase activity, GSH/GSSG ratios, and mitochondrial membrane potential. Notably, the combination of LAA and NAC consistently alleviated multiple disease-associated defects in FRDA cells, suggesting its potential as a promising therapeutic approach.},
}

*Acetylcysteine/pharmacology/therapeutic use
*Dimethyl Fumarate/pharmacology/therapeutic use
*Friedreich Ataxia/drug therapy/metabolism
*Ascorbic Acid/pharmacology/therapeutic use
Humans
Reactive Oxygen Species/metabolism
Mitochondria/drug effects/metabolism
Fibroblasts/metabolism/drug effects
Frataxin
Oxidative Stress/drug effects
Antioxidants/pharmacology/therapeutic use
Membrane Potential, Mitochondrial/drug effects
Iron-Binding Proteins/metabolism/genetics
NF-E2-Related Factor 2/metabolism
Cell Survival/drug effects

@article {pmid40374378,
year = {2025},
author = {Li, K and Wang, YJ and Wei, K and Li, WL and Liu, YB and Hu, JN and Chang, WG and Zhang, WX and Chen, L and Li, W},
title = {Ginsenoside Rg2 Alleviates HFD/STZ-Induced Diabetic Nephropathy by Inhibiting Pyroptosis via NF-κB/NLRP3 Signaling Pathways.},
journal = {The American journal of Chinese medicine},
volume = {53},
number = {3},
pages = {909-930},
doi = {10.1142/S0192415X2550034X},
pmid = {40374378},
issn = {1793-6853},
mesh = {*Ginsenosides/pharmacology/therapeutic use/administration & dosage ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Diabetic Nephropathies/drug therapy/etiology/genetics/metabolism ; *Pyroptosis/drug effects/genetics ; *Signal Transduction/drug effects/genetics ; *NF-kappa B/metabolism ; Diet, High-Fat/adverse effects ; Male ; Mice, Inbred C57BL ; Humans ; *Diabetes Mellitus, Experimental/drug therapy ; *Phytotherapy ; Streptozocin/adverse effects ; Mice ; Inflammasomes/metabolism ; Cell Line ; Panax/chemistry ; },
abstract = {Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng (Panax ginseng. C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1[Formula: see text]. In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways in vivo and in vitro, suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.},
}

*Ginsenosides/pharmacology/therapeutic use/administration & dosage
Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics
*Diabetic Nephropathies/drug therapy/etiology/genetics/metabolism
*Pyroptosis/drug effects/genetics
*Signal Transduction/drug effects/genetics
*NF-kappa B/metabolism
Diet, High-Fat/adverse effects
Male
Mice, Inbred C57BL
Humans
*Diabetes Mellitus, Experimental/drug therapy
*Phytotherapy
Streptozocin/adverse effects
Mice
Inflammasomes/metabolism
Cell Line
Panax/chemistry

@article {pmid40362589,
year = {2025},
author = {Ontawong, A and Nehra, G and Maloney, BJ and Vaddhanaphuti, CS and Bauer, B and Hartz, AMS},
title = {N-Acetylcysteine Attenuates Aβ-Mediated Oxidative Stress, Blood-Brain Barrier Leakage, and Renal Dysfunction in 5xFAD Mice.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362589},
issn = {1422-0067},
support = {1R01NS133250-24A1/NH/NIH HHS/United States ; },
mesh = {Animals ; *Oxidative Stress/drug effects ; *Blood-Brain Barrier/drug effects/metabolism ; *Acetylcysteine/pharmacology ; *Amyloid beta-Peptides/metabolism ; Mice ; *Alzheimer Disease/metabolism/drug therapy ; Mice, Transgenic ; Disease Models, Animal ; Aldehydes/metabolism ; Male ; Antioxidants/pharmacology ; Brain/metabolism/drug effects ; Kidney/drug effects/metabolism ; S100 Calcium Binding Protein beta Subunit/blood ; },
abstract = {Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) pathology and is closely linked to oxidative stress, which contributes to blood-brain barrier leakage, renal dysfunction, and cognitive decline. We investigated the effects of N-acetyl cysteine (NAC), an FDA-approved antioxidant, on oxidative stress, brain Aβ levels, barrier leakage, renal function, and cognition in 5xFAD mice. Eight-week-old 5xFAD mice were fed a rodent diet supplemented with 600 mg/kgDiet NAC for 4 weeks; wild-type (WT) mice and control 5xFAD mice were fed a regular rodent diet. We detected elevated brain and renal 4-hydroxynonenal(4-HNE) levels, reduced creatinine clearance, and increased plasma S100β levels in untreated 5xFAD mice compared to WT controls. Untreated 5xFAD mice also had higher capillary leakage, reduced P-gp activity, and impaired cognition compared to WT. NAC treatment of 5xFAD mice reduced brain Aβ40 levels, normalized 4-HNE levels to control levels, improved creatinine clearance, decreased capillary leakage, and lowered S100β plasma levels. NAC improved cognitive performance in 5xFAD mice, as shown by Y-maze. Our findings indicate that Aβ-induced oxidative stress contributes to barrier dysfunction, renal impairment, and cognitive deficits in 5xFAD mice. Notably, NAC treatment mitigates these effects, suggesting its potential as an adjunct therapy for AD and other Aβ-related pathologies by reducing oxidative stress.},
}

Animals
*Oxidative Stress/drug effects
*Blood-Brain Barrier/drug effects/metabolism
*Acetylcysteine/pharmacology
*Amyloid beta-Peptides/metabolism
Mice
*Alzheimer Disease/metabolism/drug therapy
Mice, Transgenic
Disease Models, Animal
Aldehydes/metabolism
Male
Antioxidants/pharmacology
Brain/metabolism/drug effects
Kidney/drug effects/metabolism
S100 Calcium Binding Protein beta Subunit/blood

@article {pmid40359441,
year = {2025},
author = {Goldin, D and Salani, DA and Valdes, B},
title = {N-Acetylcysteine (NAC) for Trichotillomania and Excoriation Disorder: An Overview.},
journal = {Journal of psychosocial nursing and mental health services},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/02793695-20250506-04},
pmid = {40359441},
issn = {0279-3695},
abstract = {Trichotillomania and excoriation/skin-picking disorder involve repetitive behaviors, such as hair pulling leading to hair loss or skin picking leading to skin lesions, that cause physical complications, significant mental distress, and functional impairment despite attempts to stop. Currently, no first-line pharmacological treatments are approved for these disorders, although glutamatergic agents, select antidepressants, and other medications have demonstrated some benefit. The therapeutic potential of N-acetylcysteine (NAC) is promising. NAC helps maintain glutamate homeostasis in the brain, thereby reducing compulsive and habitual behaviors. In addition, NAC is recognized as a low-risk, well-tolerated, and accessible dietary supplement with valuable therapeutic potential. Deficiencies in pharmacological protocols and lack of government controls place individuals at risk; therefore, health care providers are well positioned to provide reliable information and educate individuals to make informed decisions about their health. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].},
}

@article {pmid40356978,
year = {2025},
author = {Zhang, M and Yuan, W and Li, C and Chen, C and Liu, X and Ma, Z and Xiang, Y and Chen, G and Wang, C and Li, L and Wang, L and Xu, Z and Xu, C},
title = {Resveratrol and N-acetylcystein reduce hepatic steatosis but enhance initiation and progression of hepatocellular carcinoma by inhibiting GST-pi-MAPK axis in mice.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1574039},
pmid = {40356978},
issn = {1663-9812},
abstract = {INTRODUCTION: Accumulating evidence indicates that antioxidants promote tumor growth and metastasis after tumor onset in several cancer types. However, whether antioxidants prevent or accelerate hepatic tumorigenesis during steatosis remains unknown. Therefore, we investigated the effects of resveratrol (RES) and N-acetylcysteine (NAC) on hepatocellular carcinoma (HCC) development using two fatty liver mouse models.

METHODS: High-fat diet (HFD) plus diethylnitrosamine (DEN)- and AKT/Ras-induced primary HCC mouse models were used. The weight, liver weight ratio and the number of HCC tumors were calculated and histological features of mouse HCC tissues were analyzed using immumohistochemical staining such as hematoxylin and eosin staining. Proteomic analysis was used to screen for differences in liver cancer progression between antioxidant-treated HCC and models. Protein inhibitor recovery experiments in mice and in vitro cells validate the targets screened by proteomic analysis. The expression of GST-pi, p-JNK and p-p38 signaling molecules in HCC were investigated using Western blotting.

RESULTS: RES and NAC enhance HCC formation in both DEN/HFD and AKT/Ras mice. RES and NAC alleviate hepatosteatosis, and reduce ROS and DNA damage in mice. Proteomic analysis and protein inhibitor recovery assay demonstrated that GST-pi is a therapeutic target for antioxidant-induced hepatocellular carcinoma growth. Mechanistically, RES and NAC decreased p-JNK and p-p38, the two major mitogen-activated protein kinases, in HCC cells. Blockade of GST-pi abrogated the reduction in p-JNK and p-p38 levels and increased apoptosis of HCC cells.

CONCLUSION: Antioxidants may increase the incidence of HCC in a population with fatty liver, despite reduction in ROS production, by inhibiting GST-pi-MAPK axis.},
}

@article {pmid40311609,
year = {2025},
author = {Zheng, J and Zhang, W and Ito, J and Henkelmann, B and Xu, C and Mishima, E and Conrad, M},
title = {N-acetyl-l-cysteine averts ferroptosis by fostering glutathione peroxidase 4.},
journal = {Cell chemical biology},
volume = {32},
number = {5},
pages = {767-775.e5},
doi = {10.1016/j.chembiol.2025.04.002},
pmid = {40311609},
issn = {2451-9448},
mesh = {*Ferroptosis/drug effects ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; *Acetylcysteine/pharmacology/chemistry/metabolism ; Humans ; Lipid Peroxidation/drug effects ; },
abstract = {N-acetyl-l-cysteine (NAC) is a medication and a widely used antioxidant in cell death research. Despite its somewhat obscure mechanism of action, its role in inhibiting ferroptosis is gaining increasing recognition. In this study, we demonstrate that NAC treatment rapidly replenishes the intracellular cysteine pool, reinforcing its function as a prodrug for cysteine. Interestingly, its enantiomer, N-acetyl-d-cysteine (d-NAC), which cannot be converted into cysteine, also exhibits a strong anti-ferroptotic effect. We further clarify that NAC, d-NAC, and cysteine all act as direct reducing substrates for GPX4, counteracting lipid peroxidation. Consequently, only GPX4-rather than system xc[-], glutathione biosynthesis, or ferroptosis suppressor protein 1-is necessary for NAC and d-NAC to prevent ferroptosis. Additionally, we identify a broad range of reducing substrates for GPX4 in vitro, including β-mercaptoethanol. These findings provide new insights into the mechanisms underlying the protective effects of NAC and other potential GPX4-reducing substrates against ferroptosis.},
}

*Ferroptosis/drug effects
*Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism
*Acetylcysteine/pharmacology/chemistry/metabolism
Humans
Lipid Peroxidation/drug effects

@article {pmid40021515,
year = {2025},
author = {Dong, L and Hao, X and Liu, M and Zhai, Y and Wang, X and Tian, X and Li, W and Peng, Y and Zheng, J},
title = {Metabolic activation and cytotoxicity of ibudilast mediated by CYP3A4.},
journal = {Archives of toxicology},
volume = {99},
number = {5},
pages = {2023-2038},
pmid = {40021515},
issn = {1432-0738},
mesh = {Animals ; *Cytochrome P-450 CYP3A/metabolism ; Humans ; Microsomes, Liver/drug effects/metabolism/enzymology ; Glutathione/metabolism ; *Pyridines/toxicity/metabolism/pharmacokinetics ; Mice ; Male ; Activation, Metabolic ; *Chemical and Drug Induced Liver Injury/etiology/metabolism/pathology ; Hepatocytes/drug effects/metabolism ; Cysteine/metabolism ; Mice, Inbred C57BL ; Cell Survival/drug effects ; Acetylcysteine/metabolism ; Indolizines ; Pyrazoles ; },
abstract = {Ibudilast (IBD) is a relatively nonselective inhibitor of phosphodiesterase, commonly used for treating asthma, progressive multiple sclerosis and other neuropathological pain conditions. Although IBD was considered safe and harmless to human health, its clinical use might be associated with reported increases of serum AST and ALT as well as liver weight. However, the mechanisms behind such liver injury are still unknown. The purpose of this work was to investigate metabolic activation of IBD and to define correlation between bioactivation and hepatotoxicity of IBD. Two oxidative metabolites, IBD-derived glutathione (GSH) conjugates (M1, M2), N-acetyl-L-cysteine (NAC) conjugates (M3, M4), and cysteine (Cys) conjugates (M5, M6) were detected in mouse liver microsomes fortified with IBD (100 μM) and trapping agents GSH, NAC, or Cys, respectively, and two GSH conjugates (M1 and M2), one NAC conjugate (M4) and one Cys conjugate (M5) were detected. Similar observation was obtained in human liver microsomal incubations. The formation of M1-M6 was NADPH-dependent. Moreover, biliary GSH conjugates and urinary NAC conjugates derived from IBD were detected in mice given IBD intragastrically at 100 mg/kg. The metabolism study suggested the formation of an epoxide intermediate. In addition, the epoxide intermediate was found to react with cysteine residues of hepatic protein in a dose-dependent manner. Further studies indicate that CYP3A4 dominated the metabolic activation of IBD. Exposure of primary hepatocytes to IBD resulted in decreased cell survival. Pretreatment of mice hepatocytes with ketoconazole attenuated the susceptibility to the cytotoxicity of IBD (25-400 μM). The reactive epoxide intermediate might correlate the hepatotoxicity induced by IBD. This work revealed the reactive epoxide intermediate might correlate the hepatotoxicity induced by IBD, and would provide new insights into the mechanisms behind the adverse reactions taking place in clinical use of IBD, especially for the reported liver injury.},
}

Animals
*Cytochrome P-450 CYP3A/metabolism
Humans
Microsomes, Liver/drug effects/metabolism/enzymology
Glutathione/metabolism
*Pyridines/toxicity/metabolism/pharmacokinetics
Mice
Male
Activation, Metabolic
*Chemical and Drug Induced Liver Injury/etiology/metabolism/pathology
Hepatocytes/drug effects/metabolism
Cysteine/metabolism
Mice, Inbred C57BL
Cell Survival/drug effects
Acetylcysteine/metabolism
Indolizines
Pyrazoles

@article {pmid40352229,
year = {2025},
author = {Nasrun, MW and Ginting, TT and Siste, K and Pandelaki, J and Kekalih, A and Louisa, M and Susanto, AD and Utami, DS and Tarigan, IN and Trishna, AR and Halim, K},
title = {Efficacy of N-acetylcysteine and motivational enhancement therapy for nicotine addiction: A randomized clinical trial.},
journal = {Narra J},
volume = {5},
number = {1},
pages = {e2178},
pmid = {40352229},
issn = {2807-2618},
mesh = {Humans ; *Acetylcysteine/therapeutic use/pharmacology ; Male ; Female ; Adult ; *Tobacco Use Disorder/drug therapy/therapy ; Middle Aged ; Magnetic Resonance Spectroscopy ; Motivation ; Treatment Outcome ; Brain/metabolism/drug effects ; Creatine/metabolism ; Glutamine ; Prefrontal Cortex ; Aspartic Acid/analogs & derivatives ; },
abstract = {N-acetylcysteine (NAC) is known to enhance neuroplasticity and help reduce smoking addiction by modulating brain metabolites. The use of magnetic resonance spectroscopy (MRS) in smokers receiving NAC as an adjuvant to motivational enhancement therapy (MET) represents a novel approach to understanding how this combination therapy influences brain chemistry. By utilizing MRS, the effectiveness of NAC can be quantitatively assessed by analyzing changes in smoking-affected brain metabolites. The aim of this study was to evaluate the efficacy of NAC combined with MET for nicotine addiction, using MRS to assess neurochemical alterations associated with treatment response. A stratified, randomized, parallel-group clinical trial was conducted, comparing NAC and MET combination to MET only among smokers. The study analyzed the effectiveness of NAC by evaluating glutamate-glutamine (Glx) to creatine ratio (Glx/creatine ratio) and N-acetylaspartate (NAA) to creatine ratio (NAA/creatine ratio) in the nucleus accumbens, bilateral cerebellum, medial prefrontal cortex, ventromedial prefrontal cortex, and bilateral precuneus. Our data indicated that the Glx/creatine ratios for the intervention versus control groups were as follows: nucleus accumbens (0.68 vs 0. 43), bilateral cerebellum (0.68 vs 0.43), left medial prefrontal cortex (1.11 vs 0.82), ventromedial prefrontal cortex (0.32 vs 0.86), and bilateral precuneus (0.75 vs 0.58). The NAA/creatine ratios for the intervention versus control groups were as follows: nucleus accumbens (3.55 vs 8.35), bilateral cerebellum (7.82 vs 4.02), left medial prefrontal cortex (5.47 vs 5.20), ventromedial prefrontal cortex (3.55 vs 7.46), and bilateral precuneus (4.73 vs 4.00). Our analysis indicated that the Glx/creatine ratio was higher in the intervention group than in the control group in the medial prefrontal cortex (p = 0.02), while the NAA/creatine ratio was higher in the intervention group than in the control group in the bilateral cerebellum (p < 0.001). The reported side effects were mild to moderate discomfort and well-tolerated across both groups. These findings highlight the potential of NAC and MET combination in promoting neuroplasticity and supporting nicotine addiction treatment.},
}

Humans
*Acetylcysteine/therapeutic use/pharmacology
Male
Female
Adult
*Tobacco Use Disorder/drug therapy/therapy
Middle Aged
Magnetic Resonance Spectroscopy
Motivation
Treatment Outcome
Brain/metabolism/drug effects
Creatine/metabolism
Glutamine
Prefrontal Cortex
Aspartic Acid/analogs & derivatives

@article {pmid40350672,
year = {2025},
author = {Ma, X and Yang, Y and Liu, S and Cui, Y and Wu, J},
title = {Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility.},
journal = {Revista internacional de andrologia},
volume = {23},
number = {1},
pages = {1-12},
doi = {10.22514/j.androl.2025.004},
pmid = {40350672},
issn = {1698-0409},
support = {82370690, 82303813//National Natural Science Foundation of China/ ; ZR2023MH241, ZR2023QH271//Shandong Science and Technology Program/ ; tsqn201909199, tsqn202306403//Taishan Scholars Program of Shandong Province/ ; },
mesh = {Male ; *Acetylcysteine/therapeutic use/adverse effects ; Humans ; *Infertility, Male/drug therapy ; *Carnitine/therapeutic use/adverse effects ; Sperm Motility/drug effects ; Randomized Controlled Trials as Topic ; *Antioxidants/therapeutic use/adverse effects/administration & dosage ; Sperm Count ; Testosterone/blood ; Treatment Outcome ; Ejaculation/drug effects ; },
abstract = {BACKGROUND: Oral antioxidants especially L-carnitine (LC) and N-Acetylcysteine (NAC) are commonly used as the drug treatment method for idiopathic male infertility (IMI).

METHODS: Randomized controlled trials (RCTs) of LC and NAC monotherapy for IMI were searched systematically by using MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of retrieved studies were also perused. We analyzed the sperm concentration, normal morphology, sperm motility, and ejaculation volume.

RESULTS: Seven Randomized controlled trials were included. Four trials compared the efficacy of LC with placebo, and three trials compared the efficacy of NAC with placebo. In the efficacy analysis, LC increased sperm concentration (p < 0.001), normal morphology (p = 0.03), and sperm motility (p = 0.02); NAC improved the first three indicators while also increasing ejaculation volume (p = 0.002). In hormone level analysis, LC increased serum testosterone levels (p < 0.001), but the changes in other hormone levels were not statistically significant.

CONCLUSIONS: Both LC and NAC can improve sperm motility, sperm concentration, and normal morphology, and increase serum testosterone concentration, but have no significant effect on other serum hormones.

THE PROSPERO REGISTRATION: CRD42024552120.},
}

Male
*Acetylcysteine/therapeutic use/adverse effects
Humans
*Infertility, Male/drug therapy
*Carnitine/therapeutic use/adverse effects
Sperm Motility/drug effects
Randomized Controlled Trials as Topic
*Antioxidants/therapeutic use/adverse effects/administration & dosage
Sperm Count
Testosterone/blood
Treatment Outcome
Ejaculation/drug effects

@article {pmid40348944,
year = {2025},
author = {Kosonen, JP and Eskelinen, ASA and Orozco, GA and Coleman, MC and Goetz, JE and Anderson, DD and Grodzinsky, AJ and Tanska, P and Korhonen, RK},
title = {Mechanobiochemical finite element model to analyze impact-loading-induced cell damage, subsequent proteoglycan loss, and anti-oxidative treatment effects in articular cartilage.},
journal = {Biomechanics and modeling in mechanobiology},
volume = {},
number = {},
pages = {},
pmid = {40348944},
issn = {1617-7940},
support = {240098//Sigrid Juselius Foundation/ ; 354916//Strategic funding of the University of Eastern Finland, Academy of Finland/ ; 363459//Strategic funding of the University of Eastern Finland, Academy of Finland/ ; 240074//Päivikki and Sakari Sohlberg Foundation/ ; NNF21OC0065373//Novo Nordisk Foundation (the Center for Mathematical Modeling of Knee Osteoarthritis (MathKOA))/ ; },
abstract = {Joint trauma often leads to articular cartilage degeneration and post-traumatic osteoarthritis (PTOA). Pivotal determinants include trauma-induced excessive tissue strains that damage cartilage cells. As a downstream effect, these damaged cells can trigger cartilage degeneration via oxidative stress, cell death, and proteolytic tissue degeneration. N-acetylcysteine (NAC) has emerged as an antioxidant capable of inhibiting oxidative stress, cell death, and cartilage degeneration post-impact. However, the temporal effects of NAC are not fully understood and remain difficult to assess solely by physical experiments. Thus, we developed a computational finite element analysis framework to simulate a drop-tower impact of cartilage in Abaqus, and subsequent oxidative stress-related cell damage, and NAC treatment upon cartilage proteoglycan content in Comsol Multiphysics, based on prior ex vivo experiments. Model results provide evidence that immediate NAC treatment can reduce proteoglycan loss by mitigating oxidative stress, cell death (improved proteoglycan biosynthesis), and enzymatic proteoglycan depletion. Our simulations also indicate that delayed NAC treatment may not inhibit cartilage proteoglycan loss despite reduced cell death after impact. These results enhance understanding of the temporal effects of impact-related cell damage and treatment that are critical for the development of effective treatments for PTOA. In the future, our modeling framework could increase understanding of time-dependent mechanisms of oxidative stress and downstream effects in injured cartilage and aid in developing better treatments to mitigate PTOA progression.},
}

@article {pmid40348128,
year = {2025},
author = {Modanlo, N and Yan, X and Bourgeois, JA},
title = {Pharmacologic Management of Skin-Picking Disorder: An Updated Review.},
journal = {Journal of the Academy of Consultation-Liaison Psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaclp.2025.05.002},
pmid = {40348128},
issn = {2667-2960},
abstract = {INTRODUCTION: Skin-picking disorder (SPD), defined as a psychocutaneous condition that involves excessive picking at the skin causing marked impairment in quality of life, is commonly seen in both dermatology and psychiatry. As such, therapeutic intervention - both non-pharmacologic and pharmacologic - is essential. Given the rising prevalence of SPD and the tremendous impact it can have on quality of life, an updated review, specifically on pharmacologic options, is very much needed.

METHODS: A search through PubMed was conducted using the key words "treatment" and "skin picking" or "excoriation" in November 2024. Articles were limited to those that solely address pharmacologic treatments in skin-picking for individuals > 18-years-old, were published in the last 20 years, in the English language, and can be classified as either a clinical trial, case report/series, or cohort study.

FINDINGS: Of the 192 articles extracted from PubMed, 13 studies (289 patients) met the inclusion criteria. These articles consist of 7 case reports/series and 6 randomized controlled trials. The following medications were evaluated for treatment of SPD: selective serotonin reuptake inhibitors (SSRIs), glutamatergic drugs (N-acetyl cysteine, memantine), antiepileptics (lamotrigine, topiramate), lithium, antipsychotics (olanzapine, aripiprazole), opioid antagonists (naltrexone), and mirtazapine.

CONCLUSION: Of the medications evaluated for use in SPD, SSRIs show the most promising results in terms of mitigating the severity and frequency of skin-picking symptoms. Although habit-reversal psychotherapy has traditionally been first-line treatment, SSRIs are now increasingly being used in combination with psychotherapy when a patient presents with SPD. N-acetyl cysteine has also been well-established in the treatment of SPD. Other classes of medications that have been studied in SPD include the use of antipsychotics (often combined with antidepressants) and naltrexone. Additional studies are indicated to further expand on the current research and definitively establish the role of the less common medications, such as antiepileptics, in SPD.},
}

@article {pmid40347530,
year = {2025},
author = {Chetcuti, L and Uljarević, M and Schuck, RK and Hardan, AY and Gengoux, GW and Trembath, D and Vadgama, Y and Varcin, KJ and Vivanti, G and Whitehouse, AJO and Helton, M and Frazier, TW},
title = {Characterizing predictors of response to behavioral interventions for children with autism spectrum disorder: A meta-analytic approach.},
journal = {Clinical psychology review},
volume = {119},
number = {},
pages = {102588},
doi = {10.1016/j.cpr.2025.102588},
pmid = {40347530},
issn = {1873-7811},
abstract = {A comprehensive understanding of specific factors contributing to variability in responsiveness of children with autism to interventions is paramount for making evidence-based clinical and policy decisions. This meta-analysis examined child and family characteristics, as well as intervention design factors, associated with outcomes of behavioral interventions for children with autism. A systematic review identified 95 studies published between 1987 and 2024, encompassing 6780 children on the autism spectrum and 2150 independent effect sizes. Results indicated that stronger post-intervention effects were observed across intervention approaches for children with higher cognitive, language, and other developmental abilities, greater adaptive functioning, and fewer autism-related features. Additionally, interventions of longer duration and greater total hours were associated with stronger post-intervention outcomes. In contrast, intervention approach (Early Intensive Behavioral Intervention, Naturalistic Developmental Behavioral Interventions, or Developmental Interventions), delivery agent, and child age at intervention onset did not significantly predict the strength of post-intervention outcomes. While study methodology and reporting quality were marginally associated with predictive strength, adjusting for these factors had minimal impact on the reported findings. The insights from this meta-analysis have significant implications for the development of personalized intervention models for children with autism. These models have the potential to optimize outcomes and offer critical guidance for decision-making in both the service and policy levels, ensuring efficient and equitable allocation of resources.},
}

@article {pmid40345318,
year = {2025},
author = {Låg, M and Skuland, T and Ballangby, J and Grytting, VS and Jørgensen, RB and Snilsberg, B and Øvrevik, J and Holme, JA and Refsnes, M},
title = {Mechanisms involved in pro-inflammatory responses to traffic-derived particulate matter (PM) in THP-1 macrophages compared to HBEC3-KT bronchial epithelial cells.},
journal = {Toxicology},
volume = {},
number = {},
pages = {154174},
doi = {10.1016/j.tox.2025.154174},
pmid = {40345318},
issn = {1879-3185},
abstract = {The pro-inflammatory responses in THP-1-derived macrophages and human bronchial epithelial cells (HBEC3-KT) were examined after exposure to size-fractioned particulate matter (PM) sampled in two road tunnels. All tunnel PM samples induced release and expression of CXCL8 and IL-1β in THP-1 macrophages (50µg/mL) and HBEC3-KT cells (100µg/mL), but the potency of the samples differed between the cell types. The road tunnel PM induced pro-inflammatory responses in the macrophages to a much higher extent than diesel exhaust particles (DEP) and particles derived from the stone materials used in the asphalt. Tunnel PM induced a markedly higher increase in cytochrome P450 (CYP)1A1 expression in HBEC3-KT cells than in THP-1 macrophages. The content of organic carbon (OC) in PM correlated to the release of CXCL8 in HBEC3-KT cells, but not in THP-1 macrophages. Moreover, the aryl hydrocarbon receptor (AhR)-inhibitor CH223191 and the antioxidant N-acetyl cysteine (NAC) reduced the PM-induced cytokine release in the macrophages to a lower extent than in HBEC3-KT. In contrast, a toll-like receptor (TLR)2 antibody markedly reduced the PM-induced responses in THP-1 macrophages, but not in HBEC3-KT. A TLR4 antibody was without effect in both cell types. The levels of the microbial TLR2-ligand β-glucan in the PM samples were in a range that might be sufficient to induce pro-inflammatory responses. However, a microbial-independent mechanism could also be involved. In support of such a mechanism, the pro-inflammatory responses to a sample of α-quartz (Min-U-Sil 5), with low levels of β-glucan, were reduced by anti-TLR2. In conclusion, our results indicate that traffic-derived PM exert pro-inflammatory responses in THP-1 macrophages and HBEC3-KT cells via different PM constituents and mechanisms. OC/AhR-dependent mechanisms appeared to be important for PM-induced CXCL8 responses in HBEC3-KT cells, while the cytokine responses in THP-1 macrophages seemed to involve TLR2-mediated activation, either via β-glucan-dependent or -independent mechanisms.},
}

@article {pmid40342610,
year = {2025},
author = {Ebid, AIM and Mohamed, HS and Mohammed, YMM and Mohamed Abdel Motaleb, SM},
title = {Efficacy, Safety, and Cost-Effectiveness of N-Acetylcysteine in Preventing Amphotericin B Nephrotoxicity in Egyptian Patients with Hematological Malignancies: A Randomized Controlled Trial.},
journal = {Hospital pharmacy},
volume = {},
number = {},
pages = {00185787251337615},
pmid = {40342610},
issn = {0018-5787},
abstract = {Introduction: Amphotericin B (AmB-d) is one of the most common agents for treating fatal systemic fungal infections in patients with hematologic malignancies. However, its severe adverse effects, especially nephrotoxicity, limited its use. This study evaluated the efficacy, safety, and cost-effectiveness of oral N-acetylcysteine (NAC) in preventing AmB-d nephrotoxicity and promoting renal recovery in Egyptian hematological malignancy patients. Methods: A prospective open-label randomized controlled trial was conducted. Patients were randomized to receive AmB-d plus 600 mg NAC twice daily (intervention group) or AmB-d alone (control group). The primary outcome was the incidence of acute kidney injury (AKI), with secondary outcomes including electrolyte imbalances (hypokalemia, hypomagnesemia) and renal recovery from AKI. A cost-effectiveness analysis was performed, supported by one-way and probabilistic sensitivity analyses (PSA). Results: NAC co-treatment significantly reduced AmB-d-induced AKI (odds ratio = 0.415, 95% CI: 0.174-0.992, P = .041). Renal recovery rates were higher in the NAC group (73.33% vs 53.85%), though not statistically significant (P = .322); the number needed to treat (NNT) was 6, indicating clinical relevance. No significant differences were observed in hypokalemia (P = .547) or hypomagnesemia (P = .768). NAC was cost-effective, with an effectiveness gain of 0.22 and cost savings of 2742.678 EGP per patient. Sensitivity analyses confirmed robustness, with NAC being dominant in 942 out of 1000 PSA scenarios. NAC was well-tolerated, with only mild gastrointestinal side effects reported. Conclusion: NAC co-administration with AmB-d effectively prevents nephrotoxicity, reduces costs, and may promote renal recovery in Egyptian hematological malignancy patients. The favorable NNT for renal recovery suggests clinical relevance, warranting further investigation in larger studies. Trial registration: ClinicalTrials.gov identifier, NCT06122311.},
}

@article {pmid40341677,
year = {2025},
author = {Zhao, Y and Zhu, L and Lin, X and Li, B and Miu, B and Qiu, J and Gao, S and Liu, J},
title = {JS-K induces ferroptosis in renal carcinoma cells by regulating the c-Myc-GSTP1 Axis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {15987},
pmid = {40341677},
issn = {2045-2322},
support = {81272833//National Natural Science Funds/ ; },
mesh = {*Ferroptosis/drug effects ; Humans ; Animals ; *Carcinoma, Renal Cell/metabolism/drug therapy/pathology ; *Kidney Neoplasms/metabolism/drug therapy/pathology ; Mice ; *Proto-Oncogene Proteins c-myc/metabolism/genetics ; Cell Line, Tumor ; *Glutathione S-Transferase pi/metabolism/genetics ; Lipid Peroxidation/drug effects ; Mice, Nude ; Glutathione/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Xenograft Model Antitumor Assays ; Piperazines/pharmacology ; },
abstract = {JS-K is a precursor drug of nitric oxide (NO) and inhibits tumor growth through various mechanisms. Ferroptosis, a form of cell death closely related to lipid peroxidation, is increasingly being recognized for its role in cancer biology. However, the relevance of ferroptosis in the anti-tumor effects of JS-K is yet to be defined. The cytotoxic effects of erastin and JS-K were evaluated in various renal cell carcinoma (RCC) cell lines and normal human renal epithelial cells. Cell viability and the intracellular levels of ferrous ions, glutathione (GSH), lipid peroxides, and malondialdehyde (MDA) were measured using standard in vitro assays. The expression levels of specific proteins were analyzed by western blotting. Subcutaneous xenografts of RCC were established in a nude mouse model, and the anti-tumor effects of JS-K were assessed by histological and immunohistochemical methods. Erastin selectively inhibited the growth of RCC cells without affecting normal renal cells. In addition, JS-K induced ferroptosis in RCC cells by reducing cellular GSH levels, increasing lipid peroxidation, and elevating ferrous ion levels, and the effects of JS-K were neutralized by N-acetylcysteine (NAC). At the molecular level, JS-K downregulated GSTP1 by blocking the transcription factor c-Myc. Finally, JS-K inhibited tumor growth in a mouse model by inducing ferroptosis. JS-K induces ferroptosis in RCC cells by depleting glutathione through the inhibition of the c-Myc-GSTP1 axis.},
}

*Ferroptosis/drug effects
Humans
Animals
*Carcinoma, Renal Cell/metabolism/drug therapy/pathology
*Kidney Neoplasms/metabolism/drug therapy/pathology
Mice
*Proto-Oncogene Proteins c-myc/metabolism/genetics
Cell Line, Tumor
*Glutathione S-Transferase pi/metabolism/genetics
Lipid Peroxidation/drug effects
Mice, Nude
Glutathione/metabolism
Gene Expression Regulation, Neoplastic/drug effects
Xenograft Model Antitumor Assays
Piperazines/pharmacology

@article {pmid40340690,
year = {2025},
author = {Yang, N and Lai, Y and Yu, G and Zhang, X and Shi, J and Xiang, L and Zhang, J and Wu, Y and Jiang, X and Zhang, X and Yang, L and Gao, W and Ding, J and Wang, X and Xiao, J and Zhou, K},
title = {METTL3-dependent m[6]A modification of SNAP29 induces "autophagy-mitochondrial crisis" in the ischemic microenvironment after soft tissue transplantation.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-24},
doi = {10.1080/15548627.2025.2493455},
pmid = {40340690},
issn = {1554-8635},
abstract = {Necrosis at the ischemic distal end of flap transplants increases patients' pain and economic burden. Reactive oxygen species (ROS) and mitochondrial damage are crucial in regulating parthanatos, but the mechanisms linking disrupted macroautophagic/autophagic flux to parthanatos in ischemic flaps remain unclear. The results of western blotting, immunofluorescence staining, and a proteomic analysis revealed that the autophagic protein SNAP29 was deficient in ischemic flaps, resulting in disrupted autophagic flux, increased ROS-induced parthanatos, and aggravated ischemic flap necrosis. The use of AAV vector to restore SNAP29 in vivo mitigated the disruption of autophagic flux and parthanatos. Additionally, quantification of the total m[6]A level and RIP-qPCR, MeRIP-qPCR, and RNA stability assessments were performed to determine differential Snap29 mRNA m[6]A methylation levels and mRNA stability in ischemic flaps. Various in vitro and in vivo tests were conducted to verify the ability of METTL3-mediated m[6]A methylation to promote SNAP29 depletion and disrupt autophagic flux. Finally, we concluded that restoring SNAP29 by inhibiting METTL3 and YTHDF2 reversed the "autophagy-mitochondrial crisis", defined for the first time as disrupted autophagic flux, mitochondrial damage, mitochondrial protein leakage, and the occurrence of parthanatos. The reversal of this crisis ultimately promoted the survival of ischemic flaps.Abbreviations: AAV = adeno-associated virus; ACTA2/α-SMA = actin alpha 2, smooth muscle, aorta; AIFM/AIF = apoptosis-inducing factor, mitochondrion-associated; ALKBH5 = alkB homolog, RNA demythelase; Baf A1 = bafilomycin A1; CQ = chloroquine; DHE = dihydroethidium; ECs = endothelial cells; F-CHP = 5-FAM-conjugated collagen-hybridizing peptide; GO = gene ontology; HUVECs = human umbilical vein endothelial cells; KEGG = Kyoto Encyclopedia of Genes and Genomes; LC-MS/MS = liquid chromatography-tandem mass spectrometry; LDBF = laser doppler blood flow; m[6]A = N6-methyladenosine; MAP1LC3/LC3 = microtubule-associated protein 1 light chain 3; MeRIP = methylated RNA immunoprecipitation; METTL3 = methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit; NAC = N-acetylcysteine; OGD = oxygen glucose deprivation; PAR = poly (ADP-ribose); PARP1 = poly (ADP-ribose) polymerase family, member 1; PECAM1/CD31 = platelet/endothelial cell adhesion molecule 1; ROS = reactive oxygen species; RT-qPCR = reverse transcription quantitative polymerase chain reaction; RIP = RNA immunoprecipitation; SNAP29 = synaptosomal-associated protein 29; SNARE = soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1 = sequestosome 1; SRAMP = sequence-based RNA adenosine methylation site predicting; STX17 = syntaxin 17; TMT = tandem mass tag; TUNEL = terminal deoxynucleotidyl transferase dUTP nick end labeling; VAMP8 = vesicle-associated membrane protein 8; WTAP = WT1 associating protein; YTHDF2 = YTH N6-methyladenosine RNA binding protein 2; 3' UTR = 3'-untranslated region.},
}

@article {pmid40340419,
year = {2025},
author = {Stutts, J and Clatterbuck, K and Duckworth, C and Pemberton, T and Elkins, A and Patra, P and Stoecker, W and Geria, N and Nosoudi, N},
title = {Synergistic impact of antioxidant combinations on collagen and elastin synthesis in human dermal fibroblasts.},
journal = {Bio-medical materials and engineering},
volume = {},
number = {},
pages = {9592989251341159},
doi = {10.1177/09592989251341159},
pmid = {40340419},
issn = {1878-3619},
abstract = {The restoration of collagen and elastin in human dermal fibroblasts plays a crucial role in anti-aging and skin rejuvenation therapies. Numerous studies have examined the effects of various antioxidants on skin health, but there is limited research comparing their combined effects on collagen and elastin synthesis in human dermal fibroblasts. Objective: The objective of this study was to evaluate the individual and combined effects of N-acetylcysteine (NAC), Coenzyme Q10 (CoQ10), Niacinamide (NIAC), Gamma Cyclodextrin (GAMMA), Retinol (RET), Epigallocatechin Gallate (EGCG), and Ellagic Acid (ELA) on collagen type I and elastin synthesis in human dermal fibroblasts (HDFs). Methods: Human dermal fibroblasts were treated with individual and combined antioxidants. The expression of collagen type I and elastin was measured using mRNA analysis, immunofluorescence staining, and matrix protein assays. The study focused on the effects of EGCG in combination with other antioxidants like RET, CoQ10, and NAC to identify synergistic effects. Results: The combination of EGCG + RET and EGCG + CoQ10 showed the most significant increase in both elastin and collagen type I synthesis, surpassing the effects of individual antioxidants. EGCG demonstrated the highest fold change in elastin mRNA expression, while the combination treatments notably enhanced the extracellular matrix restoration in HDFs. Conclusion: The combination of EGCG with CoQ10, Retinol, or NAC presents a promising strategy for enhancing skin elasticity and firmness by promoting both elastin and collagen synthesis. These findings suggest that antioxidant combinations can be developed for effective anti-aging skincare formulations.},
}

@article {pmid40337403,
year = {2025},
author = {Pasam, SS and Majety, SK and Nayeem, O and Mishra, D and Chakra G, S and Singh, R and Karuchola, MP and Anumolu, A},
title = {Paraquat poisoning: a case series of 15 survivors and narrative review.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {5},
pages = {2537-2546},
pmid = {40337403},
issn = {2049-0801},
abstract = {BACKGROUND: Paraquat (PQ) poisoning is a grave concern in developing countries due to its wide availability. Acute paraquat poisoning can have both systemic and local manifestations, with mortality rates that can reach as high as 90%; pulmonary complications and multiple organ dysfunction syndromes being major causes. This case series is a unique retrospective observational study of 15 survivors from South India.

CASE PRESENTATION: The case series consists of 15 cases, with a mean age of 24.6 years (excluding outliers), that were alleged to have taken varying amounts of paraquat dichloride. Patients exhibited a diverse range of symptoms affecting multiple organ systems, with particular emphasis on kidney, liver, and lung function. Treatments included a combination of hemodialysis, targeted drug therapy in the form of N-acetyl cysteine, anti-inflammatory therapy with corticosteriods and symptomatic therapy. The case descriptions also include the details of the amount of paraquat allegedly ingested, the ingestion to hospitalization time, demographics, etc, that further help in determination of prognosis.

OVERVIEW: PQ can cause a variety of clinical signs and symptoms, including gastrointestinal, renal, hepatic, and pulmonary problems. Less commonly, it can also affect the neurological and cardiac systems. Treatment is mainly focused on reducing the effective PQ concentration in blood, as no antidote has been named till date. The paper also discusses the various treatments available, drugs and procedures, and their mechanisms. Also prognostic factors like age, amount, ingestion to hospitalization time, etc.

CONCLUSION: The study underlines the need for defined treatment protocols, prognostic factors, and enforcing restrictions on availability of this deadly poison.},
}

@article {pmid40333203,
year = {2025},
author = {St John, A and Wang, X and Chen, J and Le, J and Ringgold, K and Klug, J and White, N and Stern, S and Chung, D and Lindner, JR and López, J},
title = {N-acetylcysteine reduces von Willebrand factor multimer size and improves renal microvascular blood flow in rats after severe trauma.},
journal = {Shock (Augusta, Ga.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/SHK.0000000000002611},
pmid = {40333203},
issn = {1540-0514},
abstract = {BACKGROUND: Severe injury induces systemic microvascular impairment that reduces microvascular blood flow (MBF), even after resuscitation to normal blood pressure. These changes are associated with organ dysfunction and death, but the underlying causes and potential therapeutic approaches to address them remain unclear. Two possible contributors are hyperadhesive VWF secretion from an activated endothelium and oxidative modification of hemostatic proteins. N-acetylcysteine has been shown to address both of these processes and increase MBF in other disease states with similar features.

METHODS: Anesthetized, male Sprague-Dawley rats were subjected to a standardized polytrauma and pressure-targeted catheter hemorrhage. They then received either no treatment (Control) or a single bolus of NAC, followed by autologous whole blood transfusion. Renal MBF was measured using contrast-enhanced ultrasound (CEUS) at prespecified time points. von Willebrand factor (VWF) multimer gels and other laboratory studies were performed. Histologic analysis of vascular thrombi was also performed on uninjured tissue from rats undergoing either this trauma protocol or a sham procedure.

RESULTS: NAC increased MBF at 3 hours after resuscitation. This was accompanied by a decrease in VWF multimer size that was not seen in the Control group. Histologic data showed an overall increase in systemic thrombus burden associated with trauma.

CONCLUSIONS: NAC improves renal MBF, possibly by reducing VWF multimer size and reducing microthrombus burden. This is significant both mechanistically and therapeutically. It sheds light on the possible pathways involved in causing microvascular obstruction after trauma and identifies possible treatment approaches that could be developed further. Ultimately, targeting these pathways could move us closer to resuscitation strategies that optimize vital organ MBF.},
}

@article {pmid40333083,
year = {2025},
author = {Yang, S and Zhang, Y and Xu, J and Chen, Z and Ren, Y and Long, Y and Huang, X and Liu, J and Huang, H and Xie, S and Ma, R and Dong, Y and Fan, X and Hu, Z and Li, F},
title = {N-Acetylcysteine as a Host-Directed Therapy Against Clarithromycin-Resistant Mycobacterium abscessus.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {40333083},
issn = {2076-0817},
support = {21Y11901700//Science and Technology Commission of Shanghai Municipality/ ; 20Z11901002//Science and Technology Commission of Shanghai Municipality/ ; ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; },
mesh = {*Acetylcysteine/pharmacology/therapeutic use ; *Mycobacterium abscessus/drug effects ; *Clarithromycin/pharmacology ; Animals ; Humans ; *Mycobacterium Infections, Nontuberculous/drug therapy/microbiology/immunology ; Mice ; *Drug Resistance, Bacterial/drug effects ; *Anti-Bacterial Agents/pharmacology ; Disease Models, Animal ; THP-1 Cells ; Signal Transduction/drug effects ; Female ; },
abstract = {(1) Background: The treatment of Mycobacterium abscessus (M. abscessus) infections resistant to clarithromycin (CLR) is highly challenging. Traditional non-tuberculous mycobacteria (NTM) chemotherapy may disturb the immune homeostasis of the host by increasing oxidative stress; therefore, host-directed immunotherapy is an alternative option for infections caused by M. abscessus. (2) Method: A clinical isolate of CLR-resistant M. abscessus was screened, and then the therapeutic effects of N-acetylcysteine (NAC) against CLR-resistant M. abscessus infection were evaluated in Tohoku Hospital Pediatrics-1 (THP-1) cells and murine models. RNA sequencing and Western blot were used to profile the protective immune responses induced by NAC. The contribution of candidate signaling pathways was confirmed by the corresponding inhibitor and agonist. (3) Results: NAC immunotherapy led to a significant reduction in bacterial loads both in THP-1 cells and murine infection models, which was associated with enhanced antioxidant effects and downregulation of apoptosis signal-regulating kinase 1 (ASK1)-mitogen-activated protein ki-nase/extracellular signal-regulated kinase 3/6 (MKK3/6)-p38 mitogen-activated protein kinase (MAPK)-mediated inflammatory immune responses. The inhibitor of p38 signaling mimicked the protective effect of NAC, while the agonist attenuated it, suggesting that the p38 pathway is crucial in NAC-mediated immune protection against M. abscessus infection. (4) Conclusion: Our study suggests that NAC could be used as a host-directed therapy agent against drug-resistant M. abscessus infection.},
}

*Acetylcysteine/pharmacology/therapeutic use
*Mycobacterium abscessus/drug effects
*Clarithromycin/pharmacology
Animals
Humans
*Mycobacterium Infections, Nontuberculous/drug therapy/microbiology/immunology
Mice
*Drug Resistance, Bacterial/drug effects
*Anti-Bacterial Agents/pharmacology
Disease Models, Animal
THP-1 Cells
Signal Transduction/drug effects
Female

@article {pmid40328458,
year = {2025},
author = {Pfau, K and Callizo, J and Rossouw, P and Gabrani, C and Holz, F and Charbel Issa, P and Kellner, U and Strauss, R and Kühlewein, L and Stingl, K and Feltgen, N and Pfau, M},
title = {[Correction: N-Acetylcysteine (NAC) for Retinitis pigmentosa].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {3},
pages = {e2},
doi = {10.1055/a-2587-6864},
pmid = {40328458},
issn = {1439-3999},
}

@article {pmid40327168,
year = {2025},
author = {Zatloukal, J and Page, C and Brat, K and Svoboda, M and Voláková, E and Plutinský, M and Kopecký, M and Koblížek, V},
title = {Effect of Treatment with Mucoactive Drugs on COPD Exacerbations During 5 years of Follow-up in the Czech Republic: A Real-World Study.},
journal = {Lung},
volume = {203},
number = {1},
pages = {61},
pmid = {40327168},
issn = {1432-1750},
support = {FNOl no. 00098892//Ministerstvo Zdravotnictví Ceské Republiky/ ; no. 15/14/NAP//Ministerstvo Zdravotnictví Ceské Republiky/ ; FNOl no. 00098892//Ministerstvo Zdravotnictví Ceské Republiky/ ; FNBr no. 65269705//Ministerstvo Zdravotnictví Ceské Republiky/ ; UHHK no. 00179906//Ministerstvo Zdravotnictví Ceské Republiky/ ; UHHK no. 00179906//Ministerstvo Zdravotnictví Ceské Republiky/ ; Research Area INDI//Cooperatio Charles University, Czechia/ ; Research Area INDI//Cooperatio Charles University, Czechia/ ; },
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/drug therapy/physiopathology/diagnosis ; Male ; Czech Republic ; Female ; Aged ; Middle Aged ; Prospective Studies ; Disease Progression ; *Expectorants/therapeutic use ; Follow-Up Studies ; *Acetylcysteine/therapeutic use ; Treatment Outcome ; Forced Expiratory Volume ; Time Factors ; },
abstract = {INTRODUCTION: Studies indicate that chronic treatment with mucoactive drugs may reduce COPD exacerbation rates. This real-world, multicenter, prospective, observational study aimed to determine the effect of long-term mucoactive treatment on exacerbations in patients with COPD in the Czech Republic.

METHODS: 452 adult patients on the Czech Multicenter Research Database of COPD with post-bronchodilator FEV1 ≤ 60% of predicted value received standard of care and were followed up for 5 years. For the first 24 months, 81 patients received regular thiol-based mucoactive drugs (77 erdosteine, 4 N-acetylcysteine) at the discretion of the treating physician and 371 patients had no mucoactive treatment (control group). Erdosteine was fully reimbursed, and NAC was partially reimbursed for COPD patients. The annual number/rate of COPD exacerbations over 5 years was monitored.

RESULTS: Patients receiving mucoactive treatment for 24 months had a significantly larger reduction from baseline in all exacerbations compared to the control group (- 0.61 vs - 0.18, p = 0.026; - 0.54 vs - 0.09, p = 0.007; - 0.55 vs 0.04, p = 0.005; - 0.67 vs 0.13, p = 0.002; - 0.53 vs 0.10, p = 0.019 in the first to fifth year, respectively). The reduction in moderate exacerbations was also significantly larger in those receiving mucoactive treatment versus no mucoactive treatment. The exacerbation rate was reduced to a greater extent in the subgroups with cough or with stage 3‒4 COPD who received mucoactive treatment but was independent of the use of inhaled corticosteroids (ICS).

CONCLUSION: Mucoactive treatment for two years reduced the number of COPD exacerbations (all, moderate) over five years of follow-up. The reduction in exacerbations was more pronounced in patients with cough or with stage 3‒4 COPD but was independent of the use of ICS.},
}

Humans
*Pulmonary Disease, Chronic Obstructive/drug therapy/physiopathology/diagnosis
Male
Czech Republic
Female
Aged
Middle Aged
Prospective Studies
Disease Progression
*Expectorants/therapeutic use
Follow-Up Studies
*Acetylcysteine/therapeutic use
Treatment Outcome
Forced Expiratory Volume
Time Factors

@article {pmid40323204,
year = {2025},
author = {Plane, J and Cabral, TDD and Knoll, RM and Conrado, JEP and Vendramini, BDV and Jung, DH},
title = {N-acetylcysteine for the Prevention of Cisplatin-Induced Hearing Loss: A Systematic Review and Meta-analysis.},
journal = {Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery},
volume = {},
number = {},
pages = {},
doi = {10.1002/ohn.1272},
pmid = {40323204},
issn = {1097-6817},
abstract = {OBJECTIVE: Cisplatin is an effective antineoplastic drug used worldwide in the treatment of various malignancies. However, it is associated with side effects, including cisplatin-induced hearing loss (CIHL). N-acetylcysteine (NAC) has been suggested as a promising drug to prevent or reduce cisplatin-derived ototoxicity. To evaluate the evidence supporting the efficacy of NAC in preventing CIHL, we conducted a systematic review and meta-analysis of the literature.

DATA SOURCES: A systematic search was conducted on PubMed, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library.

REVIEW METHODS: Articles reporting the administration of systemic or transtympanic injection of NAC for CIHL prevention were considered. The outcomes of interest included the presence of hearing loss events and changes in hearing thresholds at 0.5 through 12 kHz following cisplatin treatment.

RESULTS: A total of 7 studies involving 217 patients met inclusion criteria. Of these patients, 175 received systemic administration of NAC, and the remaining received transtympanic injection of NAC. No significant differences were found in CIHL prevention between the use of either systemic or transtympanic NAC administration compared to placebo (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.54-1.19; P = .28, and RR 0.89; 95% CI 0.51-1.54; P = .67, respectively). No significant differences were found at 0.5 to 8 kHz between groups. Qualitative analyses suggested a tendency to otoprotection in ultra-high frequencies (10 and 12 kHz).

CONCLUSION: Our findings suggest that, regardless of administration route, current published evidence does not show that NAC is effective in preventing CIHL in the standard clinical audiogram range. Further studies with larger samples are needed to confirm our findings.

LEVEL OF EVIDENCE: I.},
}

@article {pmid40321407,
year = {2025},
author = {Hosseini, E and Beyranvand, Z and Schoenwaelder, SM and Farhid, F and Ghasemzadeh, M},
title = {The Reactive Oxygen Species Scavenger N-Acetyl-L-Cysteine Reduces Storage-Dependent Decline in Integrin α IIb β 3-Mediated Platelet Function, Inhibiting Pre-Activation of Integrin and Its β 3 Subunit Cleavage.},
journal = {Oxidative medicine and cellular longevity},
volume = {2025},
number = {},
pages = {7499648},
pmid = {40321407},
issn = {1942-0994},
mesh = {*Acetylcysteine/pharmacology ; Humans ; *Reactive Oxygen Species/metabolism ; *Blood Platelets/metabolism/drug effects/cytology ; *Platelet Glycoprotein GPIIb-IIIa Complex/metabolism ; *Integrin beta3/metabolism ; Platelet Activation/drug effects ; *Free Radical Scavengers/pharmacology ; Platelet Adhesiveness/drug effects ; },
abstract = {Background: Premature activation of integrin α IIb β 3 plays a central role in the induction and development of the platelet storage lesion (PSL) characterized by an exhausted platelet phenotype that affects adhesion and spreading on fibrinogen. Given the role of reactive oxygen species (ROS) in regulating platelet activation per se, we investigated the effects of a ROS scavenger on reducing the functional decline of platelet integrin α IIb β 3 during storage. Methods: Platelet-rich plasma-platelet concentrates (PRP-PCs) were either treated with ROS-reducing agents (1 mM N-acetyl-L-cysteine [NAC] or 30 μM NADPH oxidase [NOX] inhibitor, VAS2870) or kept untreated during storage. CD41/CD61 (total integrin α IIb β 3) expression and PAC-1 binding (specific to active integrin α IIb β 3 conformation) were analyzed by flow cytometry over a 5 day storage period. Molecular changes in integrin β 3 subunit were evaluated by western blotting. Platelet adhesion/spreading to fibrinogen in the presence of ROS inhibitors was also investigated during storage using fluorescence microscopy. Results: A decrease in the molecular weight of integrin β 3 subunit was observed during platelet storage, and was significantly reduced by NAC but not VAS2870, suggesting proteolytic cleavage of β 3 during storage. Further to this, ROS inhibitors decreased integrin activation and increased platelet adhesion to fibrinogen from day 3 of storage, while NAC but not VAS2870 improved platelet spreading. Conclusion: This is the first report of increasing β 3 cleavage of integrin during storage that was inversely correlated with integrin α IIb β 3-mediated platelet function. In this regard, as a generic ROS scavenger, NAC was shown to reduce defects in platelet spreading through inhibition of β 3 cleavage. This is in contrast to VAS2870 which selectively inhibits cytosolic NOX alone, suggesting that the reduced platelet function observed during storage may be due to cumulative effects of mitochondrial ROS. Taken together, these studies suggest that adding NAC to platelets may significantly preserve optimal integrin α IIb β 3 and platelet function during storage. Moreover, as a reversible scavenger, its inhibitory effect can be readily compensated after transfusion.},
}

*Acetylcysteine/pharmacology
Humans
*Reactive Oxygen Species/metabolism
*Blood Platelets/metabolism/drug effects/cytology
*Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
*Integrin beta3/metabolism
Platelet Activation/drug effects
*Free Radical Scavengers/pharmacology
Platelet Adhesiveness/drug effects

@article {pmid40319292,
year = {2025},
author = {Eswaran, S and Mascarenhas, R and Kabekkodu, SP},
title = {The ester derivative Palmitoylcarnitine abrogates cervical cancer cell survival by enhancing lipotoxicity and mitochondrial dysfunction.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {213},
pmid = {40319292},
issn = {1478-811X},
support = {6242-P8/RGCB/PMD/DBT/ SPDK/2015//Rajiv Gandhi Centre for Biotechnology, Department of Biotechnology, Ministry of Science and Technology, India/ ; },
mesh = {Humans ; *Uterine Cervical Neoplasms/pathology/metabolism ; *Mitochondria/drug effects/metabolism/pathology ; Female ; Cell Survival/drug effects ; HeLa Cells ; *Carnitine/analogs & derivatives/pharmacology ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Apoptosis/drug effects ; Extracellular Vesicles/metabolism/drug effects ; Esters ; },
abstract = {BACKGROUND: In cervical cancer (CC), Double C2 Like Domain Beta (DOC2B) functions as a metastatic suppressor. The present study aims to determine whether ectopic expression of DOC2B causes global metabolomic changes in extracellular vesicles (EVs) and corresponds with its tumor suppressive properties.

METHODS: Using a retroviral method, we first ectopically expressed DOC2B in SiHa cells, which do not normally express DOC2B.

RESULTS: We observed that ectopically expressed DOC2B significantly altered the global metabolite profile of EVs. Metabolomics identified significant enrichment of palmitoylcarnitine (PC) in EVs upon ectopic expression of DOC2B. We identified that SiHa and HeLa cells exhibited greater cytotoxicity to PC than gingival fibroblast, HaCaT, Cal27, and MCF7. PC treatment reduced the growth, proliferation, and migration of SiHa and HeLa cells, via increasing apoptosis and decreasing S-Phase cells. PC treatment resulted in morphological alterations, decreased length and number of filopodia, and expression of proteins related to cell cycle progression, proliferation, and the epithelial-to-mesenchymal transition. Further, PC treatment caused mitochondrial morphological changes, increased mitochondrial membrane potential, and decreased mtDNA content. The decreased GSH activity, glucose consumption rate, and lactate production upon PC treatment suggest that PC can induce metabolic reprogramming in CC cells. Increased oxidative stress, calcium overload, lipid droplet accumulation, mitochondrial lipotoxicity, and mitophagy suggest that PC can cause mitochondrial dysfunction. N-acetyl cysteine (NAC) treatment reversed the cytotoxic effect of PC, via decreasing lipid peroxidation rate and increasing GSH activity. PC treatment enhanced the cytotoxic effect of cisplatin in CC.

CONCLUSION: DOC2B restoration or the use of PC may be employed as a novel therapeutic approach for CC.},
}

Humans
*Uterine Cervical Neoplasms/pathology/metabolism
*Mitochondria/drug effects/metabolism/pathology
Female
Cell Survival/drug effects
HeLa Cells
*Carnitine/analogs & derivatives/pharmacology
Cell Proliferation/drug effects
Cell Line, Tumor
Apoptosis/drug effects
Extracellular Vesicles/metabolism/drug effects
Esters

@article {pmid40318637,
year = {2025},
author = {Paul, B and Merta, H and Ugrankar-Banerjee, R and Hensley, MR and Tran, S and do Vale, GD and Zacherias, L and Hewett, CK and McDonald, JG and Font-Burgada, J and Mathews, TP and Farber, SA and Henne, WM},
title = {Paraoxonase-like APMAP maintains endoplasmic-reticulum-associated lipid and lipoprotein homeostasis.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2025.04.008},
pmid = {40318637},
issn = {1878-1551},
abstract = {Oxidative stress perturbs lipid homeostasis and contributes to metabolic diseases. Though ignored when compared with mitochondrial oxidation, the endoplasmic reticulum (ER) generates reactive oxygen species requiring antioxidant quality control. Using multi-organismal profiling featuring Drosophila, zebrafish, and mammalian hepatocytes, here we characterize the paraoxonase-like C20orf3/adipocyte plasma-membrane-associated protein (APMAP) as an ER-localized antioxidant that suppresses ER lipid oxidation to safeguard ER function. APMAP-depleted cells exhibit defective ER morphology, ER stress, and lipid peroxidation dependent on ER-oxidoreductase 1α (ERO1A), as well as sensitivity to ferroptosis and defects in ApoB-lipoprotein homeostasis. Similarly, organismal APMAP depletion in Drosophila and zebrafish perturbs ApoB-lipoprotein homeostasis. Strikingly, APMAP loss is rescued with chemical antioxidant N-acetyl-cysteine (NAC). Lipidomics identifies that APMAP loss elevates phospholipid peroxidation and boosts ceramides-signatures of lipid stress. Collectively, we propose that APMAP is an ER-localized antioxidant that promotes lipid and lipoprotein homeostasis in the ER network.},
}

@article {pmid40316146,
year = {2025},
author = {Rogóż, Z and Kamińska, K and Wąsik, A},
title = {N-acetylcysteine enhances the antipsychotic effect of aripiprazole in the neurodevelopmental rat model of schizophrenia.},
journal = {Pharmacology, biochemistry, and behavior},
volume = {},
number = {},
pages = {174028},
doi = {10.1016/j.pbb.2025.174028},
pmid = {40316146},
issn = {1873-5177},
abstract = {Symptoms of schizophrenia are well characterized, but the mechanism underlying the pathogenesis of the disease still remains unknown. In addition, therapy of negative symptoms and cognitive deficits in schizophrenic patients is a serious clinical problem. Some clinical studies have shown that the atypical antipsychotic drug aripiprazole (ARI), and the antioxidant N-acetylcysteine (NAC) are effective in reducing positive and negative symptoms of schizophrenia in patients. The aim of the present study was to evaluate the influence of repeated co-treatment with low doses of ARI and NAC on the schizophrenia-like behavior in adult rats. The schizophrenia-like behavior was induced in Sprague-Dawley male pups in the neonatal days p5-p16 by repeated administration of the glutathione synthesis inhibitor L-butionine-(S,R)-sulfoximine (BSO) given together with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4-3-(3-phenylpropyl) (GBR 12909). Adult rats received repeated co-treatment with ARI (0.1 mg/kg) and NAC (10 mg/kg) for 21 days, and their effects on schizophrenia-like behavior were assessed (on p90-91) using the social interaction test and novel object recognition test. The present data indicated that the studied drugs at higher doses: ARI (0.3 mg/kg but not 0.1 mg/kg) and NAC (30 mg/kg but not 10 mg/kg) reversed schizophrenia-like symptoms in the tested model. Moreover, repeated co-treatment with low doses of ARI with NAC also reversed schizophrenia-like behavior in the neurodevelopmental rat model of schizophrenia. The above results indicated that NAC enhanced the action of ARI in the used neurodevelopmental rat model of schizophrenia, and the mechanism of action of the used drugs in this model is discussed.},
}

@article {pmid40312270,
year = {2025},
author = {Ji, R and Yang, Y and Bian, B and Zhang, Y and Wang, F and Jia, Y},
title = {Exposure to Polyethylene Terephthalate Microplastic Induces Mouse Liver Fibrosis Through Oxidative Stress and p38 MAPK/p65 NF-κB Signaling Pathway.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.4797},
pmid = {40312270},
issn = {1099-1263},
support = {42377430//National Natural Science Foundation of China/ ; 202201382//Inner Mongolia Autonomous Region Health Science and Technology Plan project/ ; HLJH202418//Bud Plan of Baotou Medical College/ ; },
abstract = {Microplastic (MP) pollution has garnered attention due to its potential impact on living organisms. Among these, polyethylene terephthalate microplastics (PET-MPs) are frequently detected in both environmental samples and human tissues. Despite this, the effects of PET-MPs on liver damage and fibrosis in mammals remain insufficiently understood. This study demonstrated that oral exposure to PET-MPs at doses of 1 mg/day (with a diameter of 1 μm) over 42 days resulted in inhibited weight gain and altered organ coefficients in male mice, suggesting possible liver damage. Using HE and Masson staining revealed pathological changes in the livers of exposed mice, such as hepatocyte swelling, inflammatory cell infiltration, and collagen deposition. Liver function tests confirmed elevated serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Further, the elevated levels of oxidative stress markers, along with the enhanced expression of proteins related to the p38 MAPK/p65 NF-κB signaling pathway as revealed by western blot analysis, both of which are strongly associated with liver damage and fibrosis. To further elucidate these mechanisms, experiments involving N-acetylcysteine (NAC) to counteract oxidative stress and SB203580 to inhibit p38 MAPK activation demonstrated that both interventions effectively mitigated liver fibrosis. Exposure to PET-MPs may trigger liver injury and fibrosis in mice. During this process, oxidative stress and the p38 MAPK/p65 NF-κB signaling pathway may play significant mediating roles.},
}

@article {pmid40311840,
year = {2025},
author = {Zhang, Z and Zhao, L and Wang, J and Chen, H and Lin, Y and Wang, F and Wang, L and Chen, J and Liu, J and Zhang, X},
title = {Luteolin, as a bidirectional ROS regulator, elevates mouse beige adipocyte browning.},
journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids},
volume = {1870},
number = {5},
pages = {159620},
doi = {10.1016/j.bbalip.2025.159620},
pmid = {40311840},
issn = {1879-2618},
abstract = {In beige adipocytes, UCP1-dependent thermogenesis can be driven by intracellular reactive oxygen species (ROS) generation. While ROS elevation also induces mast cell activation, serotonin synthesis and release from mast cells inhibits beige progenitor cell proliferation and browning. As a natural antioxidant and mast cell stabilizer, luteolin promotes adipocyte thermogenesis and inhibits mast cell activation. Thus, to activate adipocyte thermogenesis, how luteolin regulates ROS level in beige adipocytes and mast cells needs to be further investigated. In this study, mouse subcutaneous stromal vascular fraction (SVF) cells are induced to differentiate into beige adipocytes, and mouse bone marrow-derived mast cells (BMMCs) are activated with hydrogen peroxide (H2O2). Intracellular ROS level is augmented in differentiated beige adipocytes and H2O2-activated BMMCs, and H2O2-activated BMMCs inhibited brown differentiation of SVF cells and thermogenesis of beige adipocytes. In beige adipocytes, unlike synthetic antioxidant N-acetylcysteine (NAC), luteolin elevates the expression of thermogenic and beige-selective marker genes and intracellular ROS generation. Contrarily, luteolin inhibits H2O2-induced mast cell activation and ROS generation. Further, luteolin partially reverses the inhibitory effects of H2O2-activated BMMCs on the brown differentiation of SVF cells and the thermogenesis of beige adipocytes. Molecular mechanistic studies demonstrate that luteolin regulates intracellular ROS level in beige adipocytes and mast cells via the nuclear factor erythroid 2-related factor 2 (Nrf2)/Catalase pathway. Altogether, as a ROS regulator, luteolin contrarily affects intracellular ROS generation in beige adipocytes and mast cells, and hence elevates adipocyte browning.},
}

@article {pmid40302832,
year = {2025},
author = {Sunny, G and Doddwad, PK and Shenvi, S},
title = {Comparative evaluation of effect of N-acetyl cysteine, maleic acid, and ethylenediaminetetraacetic Acid on the depth of dentinal tubule penetration of an epoxy resin-based root canal sealer: A confocal laser scanning microscopy study.},
journal = {Journal of conservative dentistry and endodontics},
volume = {28},
number = {4},
pages = {309-313},
pmid = {40302832},
issn = {2950-4708},
abstract = {BACKGROUND: Effective root canal irrigation removes the smear layer for optimal sealer penetration. While 17% ethylenediaminetetraacetic Acid (EDTA) is effective, concerns about dentin erosion exist. Alternatives like 7% maleic acid (MA) and 20% N-acetylcysteine (NAC) show promise with fewer adverse effects.

AIM: To compare the effects of 20% NAC, 7% MA, and 17% EDTA as final irrigating solutions on the depth of sealer penetration into dentinal tubules at coronal, middle, and apical thirds of root canals using confocal laser scanning microscopy (CLSM).

MATERIALS AND METHODS: Sixty-six single-canal mandibular premolars free of caries, fractures, or prior treatment were selected. The teeth were decoronated to 14 mm root length using a diamond disk under water spray. Working length was determined by inserting a size 10 K-file until visible at the apical foramen, subtracting 1 mm. Root canals were instrumented up to F3 using ProTaper Universal rotary files with 1 mL of 2.5% NaOCl irrigation between files. Based on the final irrigation protocol, samples were divided into three groups (n = 22): Group 1-20% NAC, Group 2-7% MA, and Group 3-17% EDTA. Each group was irrigated with 5 mL of the respective irrigant, followed by a final rinse with 10 mL of distilled water. AH Plus sealer with 0.1% Rhodamine B was applied using a #25 Lentulo, and an F3 gutta-percha cone coated with the sealer was placed to working length, trimmed, and sealed with Cavit. Samples were incubated at 37°C and 100% humidity for 7 days to allow sealer setting. Roots were sectioned at 2, 5, and 8 mm from the apex to obtain 1 mm thick sections. Sealer penetration into dentinal tubules was evaluated using CLSM at ×10 magnification, measuring the penetration depth in micrometers from the canal wall to the point of maximum sealer infiltration using ImageJ software, measuring the longest penetration depth from the canal wall to the point of deepest sealer infiltration.

RESULTS: Sealer penetration was greatest in the coronal third, followed by the middle, with the least in the apical third (P < 0.0001). NAC demonstrated the highest mean in the coronal region (829.35 ± 85.36), while MA exhibited superior performance in the middle (522.92 ± 112.32) and apical (361.76 ± 49.03) regions. Intergroup comparisons showed superior penetration with 7% MA in the apical region (P < 0.0001). NAC and EDTA demonstrated comparable penetration across regions.

CONCLUSION: While all irrigants enhanced sealer penetration, 7% MA was most effective in the apical region. Both 7% MA and 20% NAC can serve as alternatives to 17% EDTA for final irrigation.},
}

@article {pmid40302321,
year = {2025},
author = {An, D and Jiang, X and Yang, Y},
title = {Sesamin Exerts Anti-Tumor Activity in Nasopharyngeal Carcinoma Through Inducing Autophagy and Reactive Oxygen Species Production.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {4},
pages = {26038},
doi = {10.31083/FBL26038},
pmid = {40302321},
issn = {2768-6698},
support = {81970864//National Natural Science Foundation of China/ ; Yu Wei (2018) No 2//Chongqing Middle and Youth Medical High-end Talent Studio Project/ ; Yu Wei (2021)//Chongqing Talents Project/ ; },
mesh = {*Reactive Oxygen Species/metabolism ; *Autophagy/drug effects ; Humans ; Animals ; *Lignans/pharmacology ; *Nasopharyngeal Carcinoma/metabolism/drug therapy ; Cell Line, Tumor ; Apoptosis/drug effects ; *Dioxoles/pharmacology/therapeutic use ; *Nasopharyngeal Neoplasms/metabolism/drug therapy/pathology ; Cell Proliferation/drug effects ; Mice ; Xenograft Model Antitumor Assays ; Mice, Nude ; Membrane Potential, Mitochondrial/drug effects ; Mice, Inbred BALB C ; Cell Movement/drug effects ; *Antineoplastic Agents/pharmacology ; Acetylcysteine/pharmacology ; },
abstract = {BACKGROUND: Sesamin can suppress many cancers, but its effect on nasopharyngeal carcinoma (NPC) is unclear. Herein, we set out to pinpoint the possible changes in NPC due to Sesamin.

METHODS: The biological function of NPC cells exposed to Sesamin/N-acetyl-L-cysteine (NAC)/3-Methyladenine (3-MA) was detected, followed by evaluation of reactive oxygen species (ROS) production (dichlorodihydrofluorescein diacetate staining) and mitochondrial membrane potential (MMP) (flow cytometry). Proteins pertinent to apoptosis (cleaved caspase-3, cleaved poly (ADP-ribose) polymerase 1 (PARP1)), cell cycle (Cyclin B1), and autophagy (microtubule-associated protein light chain 3 (LC3)-I, LC3-II, Beclin-1, P62) were quantified by Western blot. After the xenografted tumor model in mice was established, the tumor volume and weight were recorded, and Ki-67 and cleaved caspase-3 levels were determined by immunohistochemical analysis.

RESULTS: Sesamin inhibited viability, proliferation, cell cycle progression and migration, induced apoptosis, increased ROS production, and decreased MMP in NPC cells. Sesamin elevated cleaved caspase-3/caspase-3, cleaved PARP1/PARP1, and Beclin-1 expressions as well as LC3-II/LC3-I ratio, while diminishing Cyclin B1 and P62 levels. NAC and 3-MA abrogated Sesamin-induced changes as above in NPC cells. Sesamin inhibited the increase of the xenografted tumor volume and weight, down-regulated Ki-67, and up-regulated cleaved caspase-3 in xenografted tumors.

CONCLUSION: Sesamin exerts anti-tumor activity in NPC, as demonstrated by attenuated tumor proliferation and xenografted tumor volume and weight, as well as induced apoptosis in tumor tissues, consequent upon the promotion of autophagy and reactive oxygen species production.},
}

*Reactive Oxygen Species/metabolism
*Autophagy/drug effects
Humans
Animals
*Lignans/pharmacology
*Nasopharyngeal Carcinoma/metabolism/drug therapy
Cell Line, Tumor
Apoptosis/drug effects
*Dioxoles/pharmacology/therapeutic use
*Nasopharyngeal Neoplasms/metabolism/drug therapy/pathology
Cell Proliferation/drug effects
Mice
Xenograft Model Antitumor Assays
Mice, Nude
Membrane Potential, Mitochondrial/drug effects
Mice, Inbred BALB C
Cell Movement/drug effects
*Antineoplastic Agents/pharmacology
Acetylcysteine/pharmacology

@article {pmid40301453,
year = {2025},
author = {Karakoç, E and Halaçlı, SO and Hanelçi, RH and Ayhan, S and Eylem, CC and Nemutlu, E and Atilla, P},
title = {N-acetylcysteine stimulates organelle malfunction in endometriotic cells via IFN-gamma signaling.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {15120},
pmid = {40301453},
issn = {2045-2322},
support = {#TSA-2021-19011and # THD-2019-18110//Hacettepe University Scientific Research Unit/ ; #TSA-2021-19011and # THD-2019-18110//Hacettepe University Scientific Research Unit/ ; },
mesh = {Humans ; Female ; *Acetylcysteine/pharmacology ; *Endometriosis/metabolism/pathology/drug therapy ; *Interferon-gamma/metabolism ; *Signal Transduction/drug effects ; Endoplasmic Reticulum Stress/drug effects ; *Endometrium/metabolism/drug effects/pathology ; Mitochondria/drug effects/metabolism ; Cell Proliferation/drug effects ; *Organelles/drug effects/metabolism ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Endometriosis is a chronic inflammatory gynecologic disease characterized by the abnormal implantation of endometrial tissue outside the uterus. The inflammatory microenvironment of endometriosis is dominated by highly migratory endometriotic cells, inflammatory cells, and cytokines. There is no curative treatment other than oral contraceptives, painkillers, and surgery. N-acetyl-L-cysteine (NAC), an anti-inflammatory compound has been identified as a promising agent for endometriosis. However, it is still unclear how NAC interacts with interferon-gamma (IFN-ɣ) and common cytokines in the endometriotic microenvironment. This study aimed to investigate the effects of NAC, alone and in combination with IFN-ɣ and major cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-⍺) on endometriotic cells. For this purpose, we performed a real time-dependent cell impedance assay, Annexin V/PI and ER tracking by flow cytometry, immunofluorescence, western blotting, and metabolomic assays. Our results offered a new insight into the complex relationship between NAC and IFN-ɣ, both of which reduced endometriotic cells' proliferation, induced ER stress and mitochondrial dysfunction. In conclusion, NAC and IFN-ɣ, alter the metabolism of endometriotic cells, leading to endoplasmic reticulum stress and mitochondrial dysfunction. These findings suggest that NAC when combined with IFN-ɣ, has the potential to generate innovative therapeutic modalities for the treatment of endometriosis.},
}

Humans
Female
*Acetylcysteine/pharmacology
*Endometriosis/metabolism/pathology/drug therapy
*Interferon-gamma/metabolism
*Signal Transduction/drug effects
Endoplasmic Reticulum Stress/drug effects
*Endometrium/metabolism/drug effects/pathology
Mitochondria/drug effects/metabolism
Cell Proliferation/drug effects
*Organelles/drug effects/metabolism
Interleukin-6/metabolism
Tumor Necrosis Factor-alpha/metabolism

@article {pmid40298799,
year = {2025},
author = {Hu, J and Feng, J and Bai, Y and Yao, ZS and Wu, XY and Hong, XY and Lu, GD and Xue, K},
title = {Sucralose Promotes Benzo(a)Pyrene-Induced Renal Toxicity in Mice by Regulating P-glycoprotein.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {40298799},
issn = {2076-3921},
support = {GWVI-11.1-41//Shanghai Municipal Health Commission/ ; GWVI-11.1-41//Shanghai Municipal Health Commission/ ; },
abstract = {BACKGROUND: Sucralose and benzo(a)pyrene (B[a]P) are widespread foodborne substances known to harm human health. However, the effects of their combined exposure on kidney function remain unclear. This study aimed to investigate the mechanisms by which sucralose and B[a]P induce kidney injury through P-glycoprotein (PGP/ABCB1), a crucial protein involved in cellular detoxification.

METHODS: C57BL/6N mice were co-treated with sucralose and B[a]P for 90 days to evaluate their impact on kidney histopathology and function. In vitro experiments assessed cell viability, reactive oxygen species (ROS) levels, and B[a]P accumulation by flow cytometry. Molecular docking and cellular thermal shift assay (CETSA) were used to determine the binding affinity of sucralose to PGP. Furthermore, PCR, Western blotting, and immunohistochemistry were performed to analyze the expression of PGP and its upstream transcription factors.

RESULTS: Ninety days of co-exposure to sucralose and B[a]P significantly exacerbated renal dysfunction in mice, as evidenced by the elevated level of serum creatinine and urea nitrogen, which could be reverted by ROS scavenger N-acetyl cysteine (NAC). In vitro, sucralose promoted cellular accumulation of B[a]P, consequently enhancing B[a]P-induced cell growth inhibition and ROS production. Consistently, B[a]P accumulation was enhanced by PGP knockdown in both HK2 and HEK-293 cells. Mechanistically, sucralose can directly bind to PGP, competitively inhibiting its efflux capacity and increasing intracellular B[a]P retention. Prolonged co-exposure further downregulated PGP expression, possibly through the reductions of its transcriptional regulators (PXR, NRF2, and NF-κB).

CONCLUSIONS: Co-exposure to sucralose and B[a]P exacerbates renal injury by impairing PGP function. Mechanistically, sucralose inhibits PGP activity, resulting in the accumulation of B[a]P within renal cells. This accumulation triggers oxidative stress and inhibits cell growth, which demonstrates that sucralose potentiates B[a]P-induced nephrotoxicity by directly inhibiting PGP-mediated detoxification pathways, thus underscoring the critical need to evaluate toxicity risks associated with combined exposure to these compounds.},
}

@article {pmid40296602,
year = {2025},
author = {Cheng, Y and Chen, HJ and Yang, T},
title = {[Influences of dihydromyricetin on proliferation and apoptosis of chondrocytes in osteoarthritis induced by H2O2 through ROS/p38-MAPK signal pathway].},
journal = {Zhongguo gu shang = China journal of orthopaedics and traumatology},
volume = {38},
number = {4},
pages = {396-402},
doi = {10.12200/j.issn.1003-0034.20230237},
pmid = {40296602},
issn = {1003-0034},
mesh = {Animals ; *Chondrocytes/drug effects/cytology/metabolism ; *Apoptosis/drug effects ; *Hydrogen Peroxide/toxicity ; *Osteoarthritis/metabolism/drug therapy/physiopathology ; Mice, Inbred C57BL ; *Reactive Oxygen Species/metabolism ; Mice ; *Flavonols/pharmacology ; *p38 Mitogen-Activated Protein Kinases/metabolism/genetics ; *Cell Proliferation/drug effects ; Male ; Signal Transduction/drug effects ; *MAP Kinase Signaling System/drug effects ; Cells, Cultured ; },
abstract = {OBJECTIVE: To analyze the influences of dihydromyricetin on the proliferation and apoptosis of chondrocytes in osteoarthritis induced by hydrogen peroxide (H2O2) through reactive oxygen species (ROS)/p38 mitogen activated protein kinase (p38-MAPK) pathway.

METHODS: Five C57BL/6J mice were euthanized by cervical dislocation after anesthesia. Chondrocytes were extracted and cultured.After passage, the chondrocytes were divided into control group, H2O2 group (0.8 μmol·L[-1] H2O2), dihydromyricetin low concentration group (0.8 μmol·L[-1] H2O2+20 μmol·L[-1] dihydromyricetin), dihydromyricetin high concentration group (0.8 μmol·L[-1] H2O2+80 μmol·L[-1] dihydromyricetin), and ROS inhibitor N-acetylcysteine (NAC) group (0.8 μmol·L[-1] H2O2+5 mmol·L[-1] NAC). The activity of chondrocytes was measured by methyl thiazolyl tetrazolium (MTT) assay. The apoptosis rate of chondrocytes was measured by Hoechst 33342 method. The level of ROS in chondrocytes was measured by 2, 7-dichlorofluorescein diacetate (DCFH-DA) fluorescence probe.The level of Type II collagen α1 (Col2α1) mRNA was measured by qRT-PCR.And the expression of Col2α1, p-p38-MAPK/p38-MAPK, B cell lymphoma gene-2 (Bcl-2) and Bcl-2 associated X protein (Bax) proteins was detected by Western blot.

RESULTS: The chondrocytes showed swirling fibrous mass, and the expression of COL2α was positive. Compared with the control group, the chondrocyte viability, apoptosis rate, ROS fluorescence intensity, p-p38-MAPK/p38-MAPK, and the expression of Bax protein in H2O22 group increased, the level of Col2α1 mRNA, and the expression of Col2α1 and Bcl-2 proteins decreased (P<0.05). Compared with H2O2 group, the chondrocyte viability, apoptosis rate, ROS fluorescence intensity, p-p38-MAPK/p38-MAPK, and the expression of Bax protein in dihydromyricetin low concentration group, dihydromyricetin high concentration group, and NAC group decreased, the level of Col2α1 mRNA, and the expression of Col2α1 and Bcl-2 proteins increased (P<0.05).

CONCLUSION: Dihydromyricetin may inhibit chondrocyte apoptosis, inflammatory reaction and oxidative stress by inhibiting ROS/p38-MAPK pathway. Dihydromyricetin may be a potential drug for treating osteoarthritis.},
}

Animals
*Chondrocytes/drug effects/cytology/metabolism
*Apoptosis/drug effects
*Hydrogen Peroxide/toxicity
*Osteoarthritis/metabolism/drug therapy/physiopathology
Mice, Inbred C57BL
*Reactive Oxygen Species/metabolism
Mice
*Flavonols/pharmacology
*p38 Mitogen-Activated Protein Kinases/metabolism/genetics
*Cell Proliferation/drug effects
Male
Signal Transduction/drug effects
*MAP Kinase Signaling System/drug effects
Cells, Cultured

@article {pmid39800517,
year = {2025},
author = {Wang, YS and Dong, C and Zou, L and Zhao, L and Qin, JH and Mo, HL},
title = {Ligand engineering boosts catalase-like activity of gold nanoclusters for cascade reactions combined with glucose oxidase in ZIF-8 matrix.},
journal = {Analytica chimica acta},
volume = {1337},
number = {},
pages = {343565},
doi = {10.1016/j.aca.2024.343565},
pmid = {39800517},
issn = {1873-4324},
mesh = {*Glucose Oxidase/metabolism/chemistry ; *Gold/chemistry/metabolism ; *Metal Nanoparticles/chemistry ; *Catalase/metabolism/chemistry ; *Zeolites/chemistry ; Glucose/metabolism/analysis ; *Metal-Organic Frameworks/chemistry ; Ligands ; Hydrogen Peroxide/chemistry/metabolism ; Acetylcysteine/chemistry ; Imidazoles ; },
abstract = {BACKGROUND: Integrating natural enzymes and nanomaterials exhibiting tailored enzyme-like activities is an effective strategy for the application of cascade reactions. It is essential to develop a highly efficient and robust glucose oxidase-catalase (GOx-CAT) cascade system featuring controllable enzyme activity, a reliable supply of oxygen, and improved stability for glucose depletion in cancer starvation therapy. However, the ambiguous relationship between structure and performance, and the difficulty in controlling enzyme-mimic activity, significantly hinder their broader application. Herein, the CAT-like activity of atomically precise Au25(MPA)18 (MPA = 3-mercaptopropionic acid) nanoclusters (AuNCs) was modulated by incorporating N-acetyl-l-cysteine (NAC) in a series of ratio.

RESULTS: It is found that Au25(NAC)14-17(MPA)4-1 exhibited superior CAT-like activity and structural stability than Au25(MPA)18 owing to the intramolecular hydrogen bond in NAC. Moreover, the synergetic effects of glucose-depletion catalyzed by GOx, oxygen generation from the intermediate hydrogen peroxide (H2O2) facilitated by Au25(NAC)14-17(MPA)4-1, and protective function and nanoconfinement effect of zeolitic imidazolate framework-8 (ZIF-8) enabled the GOx-Au25(NAC)14-17(MPA)4-1@ZIF-8 composite to degrade more glucose. Compared to that treated with a single enzyme or free enzymes, the residual intermediate H2O2 level after treatment with GOx-Au25(NAC)14-17(MPA)4-1@ZIF-8 was about 93 % lower than that after treatment with GOx alone. This composite showed higher catalytic activity, stability, and tolerance when applied to GOx-mediated glucose depletion.

SIGNIFICANCE: In brief, the study provides a feasible strategy for realizing robust and efficient cascade reaction by integrating the merits of natural enzymes and atomically precise metal NCs with adjustable enzyme-like activity. This research offers essential guidance for developing a biocompatible and tailored cascade system.},
}

*Glucose Oxidase/metabolism/chemistry
*Gold/chemistry/metabolism
*Metal Nanoparticles/chemistry
*Catalase/metabolism/chemistry
*Zeolites/chemistry
Glucose/metabolism/analysis
*Metal-Organic Frameworks/chemistry
Ligands
Hydrogen Peroxide/chemistry/metabolism
Acetylcysteine/chemistry
Imidazoles

@article {pmid40295625,
year = {2025},
author = {Lee, SO and Joo, SH and Lee, NY and Cho, SS and Yoon, G and Kim, KT and Choi, YH and Park, JW and Choi, JS and Shim, JH},
title = {Isoalantolactone induces the apoptosis of oxaliplatin-resistant human colorectal cancer cells mediated by ROS generation and activation of JNK and p38 MAPK.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {14912},
pmid = {40295625},
issn = {2045-2322},
support = {RS-2024-00336900//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Reactive Oxygen Species/metabolism ; Oxaliplatin/pharmacology ; *Apoptosis/drug effects ; *p38 Mitogen-Activated Protein Kinases/metabolism ; *Colorectal Neoplasms/metabolism/pathology/drug therapy ; HCT116 Cells ; *Drug Resistance, Neoplasm/drug effects ; Membrane Potential, Mitochondrial/drug effects ; *Antineoplastic Agents/pharmacology ; *JNK Mitogen-Activated Protein Kinases/metabolism ; Cell Survival/drug effects ; Cell Proliferation/drug effects ; Enzyme Activation/drug effects ; Caspases/metabolism ; Sesquiterpenes ; },
abstract = {Treating colorectal cancer (CRC) poses challenges due to the lack of specific molecular targets. Although oxaliplatin (Ox) is commonly used to treat CRC, resistance frequently develops, necessitating the discovery of new therapeutics. This study explored the anticancer effects of Isoalantolactone (IAL) on human CRC cells HCT116 and Ox-resistant HCT116 (HCT116-OxR). Apoptosis, ROS generation, cell cycle distribution, mitochondrial membrane potential (MMP), and caspase activation were assessed through flow cytometry. Protein levels were determined by Western blot analysis. IAL reduced cell viability, measured by MTT assay, and inhibited anchorage-independent colony formation in CRC cells in a time- and concentration-dependent manner. The IC50 values for 48 h of incubation were below 10 µM. Annexin V/7-AAD double staining demonstrated that IAL induced apoptosis in HCT116 and HCT116-OxR cells, and Western blot analysis confirmed increased phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK). The inhibition of these kinases by SP600125 or SB203580 blocked the antiproliferative effects of IAL. Additionally, IAL triggered ROS generation and disrupted mitochondrial membranes, leading to caspase activation. Pretreatment with N-acetylcysteine (NAC) or Z-VAD-FMK inhibited the antiproliferative effects of IAL, highlighting the crucial roles of ROS generation and caspase activation in IAL-induced apoptosis in CRC cells. In summary, IAL exhibited anticancer effects in CRC cells by inducing apoptosis by elevating ROS level and activating JNK and p38 MAPK. These findings warrant further study to evaluate the therapeutic potential of IAL in treating CRC with various resistances.},
}

Humans
*Reactive Oxygen Species/metabolism
Oxaliplatin/pharmacology
*Apoptosis/drug effects
*p38 Mitogen-Activated Protein Kinases/metabolism
*Colorectal Neoplasms/metabolism/pathology/drug therapy
HCT116 Cells
*Drug Resistance, Neoplasm/drug effects
Membrane Potential, Mitochondrial/drug effects
*Antineoplastic Agents/pharmacology
*JNK Mitogen-Activated Protein Kinases/metabolism
Cell Survival/drug effects
Cell Proliferation/drug effects
Enzyme Activation/drug effects
Caspases/metabolism
Sesquiterpenes

@article {pmid40292267,
year = {2025},
author = {Zolfaghari Farajerdi, M and Rajabian, F and Razavi, BM and Ghasemzadeh Rahbarda, M and Khajavi Rad, A and Amoueian, S and Hosseinzadeh, H},
title = {Evaluating the effect of crocin on contrast-induced nephropathy in rats.},
journal = {Avicenna journal of phytomedicine},
volume = {15},
number = {2},
pages = {920-932},
pmid = {40292267},
issn = {2228-7930},
abstract = {OBJECTIVE: Contrast-induced nephropathy (CIN) raises the risk of renal injury, but crocin, a saffron component, may improve kidney function. This study investigated crocin's protective effects against CIN in rats.

MATERIALS AND METHODS: Male Wistar rats were divided into eight groups: Sham, Control, Contrast medium (diatrizoate), Diatrizoate combined with crocin at 10, 20, or 40 mg/kg/day, Diatrizoate combined with N-acetylcysteine (NAC) at 125 mg/kg/day, and Crocin alone at 40 mg/kg/day. Water deprivation began on day 5 for 48 hr, except for the sham and crocin alone groups. Indomethacin and N(ω)-nitro-L-arginine methyl ester were administered after 40 hr of dehydration. Rats were sacrificed on the eighth day, and blood and kidney samples were collected.

RESULTS: Diatrizoate increased serum creatinine and blood urea nitrogen levels, elevated malondialdehyde levels, and reduced glutathione in renal tissue. Crocin reversed these effects. Diatrizoate caused severe tubular necrosis, proteinaceous casts, medullary congestion, and interstitial edema in kidney tissue. Crocin (20 and 40 mg/kg) significantly reduced tubular necrosis, and doses of 10 and 40 mg/kg reduced interstitial edema. NAC significantly improved histopathological damage, biochemical factors, and oxidative stress. The crocin alone group showed no significant changes.

CONCLUSION: Diatrizoate induces nephrotoxicity by enhancing oxidative stress in rats, and crocin has a protective effect against it. Crocin mitigates both tissue and biochemical damage inflicted by diatrizoate.},
}

@article {pmid40289970,
year = {2025},
author = {Jiang, L and Lu, Y and Zhao, H and He, W},
title = {Arctigenin Suppresses Melanoma via Mitophagy Activation In vitro and Enhances Dacarbazine Sensitivity In vivo.},
journal = {Current cancer drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680096373796250414062644},
pmid = {40289970},
issn = {1873-5576},
abstract = {OBJECTIVE: This study aimed to investigate the effect and mechanism of arctigenin (ARG) on the sensitization of dacarbazine (DTIC) via the regulation of mitophagy.

METHODS: In vitro experiments were conducted to explore the effects of ARG on the biologi-cal behavior of melanoma cells, mitochondrial autophagy mediated by PINK1/Parkin, and the role of reactive oxygen species (ROS)-mitochondrial autophagy in the regulation of the biological behavior of melanoma cells by an ROS quenching agent, a mitochondrial autoph-agy inhibitor, and an activator. The effects of ARG and dacarbazine in nude mice were as-sessed.

RESULTS: CCK8 assays revealed that ARG inhibited the proliferation of the human melanoma cell lines A375 and SK-MEL-2. The observation of submicroscopic structures demonstrated mitochondrial damage. Flow cytometry further verified that ARG induced apoptosis. West-ern blot analysis revealed that the protein expression levels of cleaved caspase 3 and Bax in-creased, whereas that of Bcl-2 decreased. In addition, ARG increased ROS levels. LC3II/I, PINK1, and Parkin were increased. ARG-induced apoptosis was related to increased mito-chondrial oxidative stress and promoted the occurrence of mitochondrial autophagy. After the addition of the autophagy inhibitor Mdivi-1 or the ROS quencher N-acetylcysteine (NAC), the antiproliferative effect of ARG was markedly attenuated. The expression levels of PINK1, Parkin, LC3II/I, cleaved caspase 3, and Bax were increased, whereas that of Bcl-2 was decreased. The formation of mitochondrial autophagosomes was observed by transmis-sion electron microscopy. ARG inhibited the proliferation and induced the apoptosis of mel-anoma cells in vivo.

CONCLUSION: Autophagy-mediated cell apoptosis was activated through the PINK1/Parkin pathway by ARG, effectively inhibiting the proliferation of human melanoma cells.},
}

@article {pmid40288286,
year = {2025},
author = {Dai, A and Liu, X and Chen, Y and Wang, Y and Qi, H and Zeng, Y and Li, J},
title = {Co-exposure to ozone and polystyrene nanoplastic exacerbates cognitive impairment and anxiety-like behavior by regulating neuronal pyroptosis in mice.},
journal = {Environment international},
volume = {199},
number = {},
pages = {109501},
doi = {10.1016/j.envint.2025.109501},
pmid = {40288286},
issn = {1873-6750},
abstract = {Ozone (O3) and nanoplastics (NPs) are pervasive environmental pollutants that frequently co-occur in our heavily industrialized era. While it has been documented that exposure to O3 or NPs individually has neurotoxic effects, studies investigating their combined impact and the hazardous mechanisms resulting from co-exposure are limited. In this study, we established a mouse model co-exposure to polystyrene nanoparticles (PS-NPs) and O3, focusing on the prefrontal cortex (PFC), a brain region crucial for cognition and emotion. We examined the effects of O3 and PS-NPs on behavioral changes related to learning, memory, and anxiety, employing transcriptome sequencing alongside molecular and histopathological methods. Our findings indicate that combined exposure to O3 and PS-NPs disrupts the integrity of the blood-brain barrier, reducing Claudin 5 expression and leading to increased accumulation of PS-NPs in the PFC. Transcriptome sequencing demonstrated the involvement of the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and oxidative stress in the pathological changes observed in the PFC. Through immunohistochemical and immunofluorescence analysis, we observed enhanced microglial activation, which correlates with increased production of inflammatory factors. Additionally, western blot and immunofluorescence co-labeling analyses revealed elevated expression levels of GSDMD-N, caspase-1, IL-1β, and IL-18 proteins, which are associated with neuronal pyroptosis. Finally, immunofluorescence co-labeling confirmed that the activation of the p38 MAPK pathway in neurons is involved in co-exposure-induced pyroptosis. Meanwhile, N-Acetylcysteine (NAC), a common antioxidant, can alleviate neuroinflammation and neuronal pyroptosis in the PFC, and it rescued the cognitive deficits and anxiety-like behaviors observed in the co-exposed mice. Our study illustrates that co-exposure to O3 and NPs can aggravate damage to the blood-brain barrier and elevate oxidative stress levels in the PFC, thereby increasing the occurrence of neuroinflammation and may mediate neuronal pyroptosis through activation of the p38 MAPK pathway, ultimately contributing to neurobehavioral toxicity.},
}

@article {pmid40284514,
year = {2025},
author = {Polo-Montalvo, A and Gómez-Cerezo, N and Cicuéndez, M and González, B and Izquierdo-Barba, I and Arcos, D},
title = {Osteogenic and Antibacterial Response of Levofloxacin-Loaded Mesoporous Nanoparticles Functionalized with N-Acetylcysteine.},
journal = {Pharmaceutics},
volume = {17},
number = {4},
pages = {},
pmid = {40284514},
issn = {1999-4923},
support = {PID2020-117091RB-I00, AEI /10.13039/501100011033//Ministerio de Ciencia e Innovación/ ; Nano4Infection, FD5/22_01//Fundación Ramón Areces, SPAIN/ ; PID2023-149093OB-I00, MCIU/AEI/10.13039/501100011033/FEDER,UE//Ministerio de Ciencia e Innovación/ ; },
abstract = {Background/Objectives: Bone infection is one of the most prevalent complications in orthopedic surgery. This pathology is mostly due to bacterial pathogens, among which S. aureus stands out. The formation of a bacterial biofilm makes systemic treatment with antibiotics ineffective. Herein we propose a nanosystem composed of mesoporous bioactive glass nanoparticles (MBGN) loaded with levofloxacin and functionalized with N-acetylcysteine (NAC), aiming to offer an alternative to current treatments. These nanoparticles would present antibacterial activity able to disintegrate the biofilm and regenerate the peri-implantar osseous tissue. Methods: MBGN of composition 82.5 SiO2-17.5 CaO have been synthesized, loaded with levofloxacin, and functionalized with NAC (MBGN-L-NAC). The antimicrobial activity against mature S. aureus biofilms and bioactivity of the nanosystem have been evaluated, as well as its biocompatibility and ability to promote murine pre-osteoblastic MC3T3-E1 differentiation. Results: MBGNs exhibited high surface areas and radial mesoporosity, allowing up to 23.1% (% w/w) of levofloxacin loading. NAC was covalently bound keeping the mucolytic thiol group, SH, available. NAC and levofloxacin combination enhances the activity against S. aureus by disrupting mature biofilm integrity. This nanosystem was biocompatible with pre-osteoblasts, enhanced their differentiation towards a mature osteoblast phenotype, and promoted bio-mimetic mineralization under in vitro conditions. MBGN-L-NAC nanoparticles induced greater osteogenic response of osteoprogenitor cells through increased alkaline phosphatase expression, increased mineralization, and stimulation of pre-osteoblast nodule formation. Conclusions: MBGN-L-NAC exhibits a more efficient antibacterial activity due to the biofilm disaggregation exerted by NAC, which also contributes to enhance the osteoinductive properties of MBGNs, providing a potential alternative to conventional strategies for the management of bone infections.},
}

@article {pmid40284511,
year = {2025},
author = {Meadows, I and Mvungi, H and Salim, K and Kaswaga, O and Mbelele, P and Liyoyo, A and Semvua, H and Ngoma, A and Heysell, SK and Mpagama, SG},
title = {N-Acetylcysteine to Reduce Kidney and Liver Injury Associated with Drug-Resistant Tuberculosis Treatment.},
journal = {Pharmaceutics},
volume = {17},
number = {4},
pages = {},
pmid = {40284511},
issn = {1999-4923},
support = {TMA2016SF-1463//EDCTP/ ; 1T32AI007046-24A44/NH/NIH HHS/United States ; },
abstract = {Background: New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated. Method: A randomized controlled trial was conducted at Kibong'oto Infectious Diseases Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences. Results: A total of 66 patients (mean age 47 ± 12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice-daily group (p > 0.99). Severe AEs were observed in four patients in the standard group, two in the NAC 900 mg daily group, and three in the NAC 900 mg twice-daily group. Renal toxicity was more prevalent in the standard treatment group compared to those that received NAC (45% vs. 23%; p = 0.058), with a shorter onset of time to toxicity (χ[2] = 3.199; p = 0.074). Liver injury events were rare across all groups. Conclusion: Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.},
}

@article {pmid40277294,
year = {2025},
author = {Li, F and Gao, S and Ma, R and Zhang, Y and Li, Y and Wu, D and Han, Z and Li, Q and He, Q and Li, J and Dai, Q and Xu, AD and Zhang, L and Liu, C and Lu, Y},
title = {Polymer-Encapsulated Catalase for Targeted Redox Regulation in Acute Liver Injury.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e2412349},
doi = {10.1002/smll.202412349},
pmid = {40277294},
issn = {1613-6829},
support = {YDZJSX2024B011//Shanxi Province Central Government Guidance Fund for Local Science and Technology Development/ ; 2024AOXIANG02//Project for Scientific Breakthroughs at Shanxi Bethune/ ; 2022YFC2104800//Key Technologies Research and Development Program/ ; L234016//National Natural Science Foundation of China-Nuclear Technology Innovation Joint Fund/ ; },
abstract = {The liver plays a critical role in maintaining homeostasis, and its dysfunction can lead to severe conditions like acute liver injury (ALI), which is primarily caused by viral infections, toxins, and oxidative stress. Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), significantly drive hepatocyte injury, initiating oxidative stress and inflammation. Current antioxidants, such as N-acetylcysteine (NAC) and superoxide dismutase (SOD), show limited clinical efficacy due to poor targeting, instability, and toxicity. Catalase (CAT), an essential enzyme for H2O2 decomposition, represents a promising therapeutic for ALI; however, its clinical application faces challenges in stability, rapid degradation, and insufficient targeting. Here, a novel nanocapsule-based CAT delivery system (n(CAT)) is presented, formed through in situ radical polymerization using 2-methacryloyloxyethyl phosphorylcholine (MPC) and N-(3-aminopropyl)-methacrylamide hydrochloride (APM). This strategy significantly enhances CAT's stability, retains enzyme activity, and improves selective liver accumulation, particularly at inflammation sites. The results demonstrate that n(CAT) effectively reduces oxidative stress, minimizes inflammation, and facilitates liver repair in ALI and ischemia-reperfusion injury (IRI) models. These findings highlight the potential of n(CAT) as a promising platform for advanced antioxidant therapies targeting liver diseases, including hepatitis.},
}

@article {pmid40277148,
year = {2025},
author = {Tuset, MP and Cooper, JN and Ebode, D and Mittal, J and Garnham, C and Melchionna, T and Hessler, R and Schilp, S and Godur, D and McKenna, K and Mittal, R and Eshraghi, AA},
title = {Intracochlear Drug Delivery Using a Catheter and Dexamethasone-Eluting Electrode Preserves Residual Hearing Post-Cochlear Implantation.},
journal = {Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery},
volume = {},
number = {},
pages = {},
doi = {10.1002/ohn.1252},
pmid = {40277148},
issn = {1097-6817},
abstract = {OBJECTIVES: This study aims to assess the feasibility and safety of a cochlear catheter (cannula) for inner ear drug delivery during cochlear implantation. We evaluated the otoprotective effect of L-N-acetylcysteine (L-NAC) administered via a cannula in combination with a dexamethasone-eluting cochlear implant (CI).

STUDY DESIGN: An animal model study.

SETTING: Animal facility of an academic institution.

METHODS: Animals were divided into 8 groups: (1) implantation with a CI; (2) implantation with a dexamethasone-eluting CI (CIDexel); (3) cannula injection of artificial perilymph (Can+AP); (4) cannula injection of Ringer (Can+R); (5) cannula injection of R and CI (Can+CI); (6) cannula injection of R and Dexel (Can+Dexel); (7) cannula injection of 2 mM L-NAC and CI (Can L-NAC 2 mM+CI); or (8) cannula injection of 2mM L-NAC and Dexel (Can L-NAC 2 mM++Dexel). The contralateral ear served as the control group. Hearing thresholds were determined preoperatively, and at postoperative day (POD 7) and POD 30 post-cochlear implantation, using auditory brainstem responses (ABRs). The organ of Corti dissections were performed at POD 30 for hair cell (HC) viability, and oxidative stress assessment using immunostaining.

RESULTS: The L-NAC (2 mM) and dexamethasone-eluting electrode group had significantly lower hearing thresholds than the standard CI, Can L-NAC 2 mM, and Dexel groups. The animal group treated with L-NAC (2 mM) and dexamethasone-eluting electrode showed higher HC viability and reduced oxidative stress.

CONCLUSION: An intracochlear cannula can deliver pharmaceutical interventions without causing additional hearing loss. L-NAC presents strong anti-apoptotic potential and administration through a cannula together with Dexel implantation, and achieves a synergistic effect enhancing the otoprotection.},
}

@article {pmid39714274,
year = {2025},
author = {Huang, KT and Tsai, WH and Chen, CW and Hwang, YS and Cheng, HC and Yeh, CW and Lin, YH and Cheng, AJ and Chang, HC and Lin, SJ and Yen, MC and Chang, WT},
title = {Hyperoxia induces autophagy in pulmonary epithelial cells: insights from in vivo and in vitro experiments.},
journal = {Free radical research},
volume = {59},
number = {1},
pages = {9-22},
doi = {10.1080/10715762.2024.2446321},
pmid = {39714274},
issn = {1029-2470},
mesh = {*Autophagy/drug effects ; Humans ; Animals ; *Hyperoxia/pathology/metabolism ; Rats ; A549 Cells ; *Epithelial Cells/metabolism/pathology/drug effects ; Reactive Oxygen Species/metabolism ; Acetylcysteine/pharmacology ; *Lung/pathology/metabolism ; Oxidative Stress ; Rats, Sprague-Dawley ; Membrane Potential, Mitochondrial/drug effects ; },
abstract = {Patients with hypoxemia require high-concentration oxygen therapy. However, prolonged exposure to oxygen concentrations 21% higher than physiological concentrations (hyperoxia) may cause oxidative cellular damage. Pulmonary alveolar epithelial cells are major targets for hyperoxia-induced oxidative stress. In this study, we evaluated the therapeutic potential of the antioxidant N-acetyl-L-cysteine (NAC) for preventing hyperoxia-induced cell death. In vitro experiments were performed using the human lung cancer cell line A549. In brief, NAC-treated and untreated cells were exposed to various concentrations of oxygen (hyperoxia) for different durations. The results indicated that hyperoxia inhibited proliferation and caused cell cycle arrest in A549 cells. It also induced necrosis and autophagy. Furthermore, hyperoxia increased intracellular reactive oxygen species levels and altered mitochondrial membrane potential. Co-treatment with NAC improved the survival of cells exposed to 95% oxygen for 24 h. Experiments performed using a neonatal rat model of acute lung injury confirmed that hyperoxia induced an autophagic response. This study provides evidence for hyperoxia-induced autophagy both in vitro and in vivo. NAC can protect A549 cells from death induced by short-term hyperoxia. Our findings may inform protective strategies against hyperoxia-induced injury in developing lungs-for example, bronchopulmonary dysplasia in premature infants.},
}

*Autophagy/drug effects
Humans
Animals
*Hyperoxia/pathology/metabolism
Rats
A549 Cells
*Epithelial Cells/metabolism/pathology/drug effects
Reactive Oxygen Species/metabolism
Acetylcysteine/pharmacology
*Lung/pathology/metabolism
Oxidative Stress
Rats, Sprague-Dawley
Membrane Potential, Mitochondrial/drug effects

@article {pmid40275972,
year = {2024},
author = {Keshavarz, S and Reisi, M and Keivanfar, M and Rabbani, F and Sabzghabaee, AM},
title = {Efficacy of Adding Oral N acetyl Cysteine Supplement to the Cystic Fibrosis Treatment Regimen: A Randomized Quasi-Experimental Trial.},
journal = {Journal of research in pharmacy practice},
volume = {13},
number = {3},
pages = {72-77},
pmid = {40275972},
issn = {2319-9644},
abstract = {OBJECTIVE: This study investigated the efficacy of adding the oral N-acetyl cysteine (NAC) supplement to the cystic fibrosis (CF) treatment regimen compared to adding a placebo. It also studied the quality of life and respiratory indicators of patients aged 6-18 with mild-to-moderate pulmonary involvement.

METHODS: This clinical trial was a randomized, quasi-experimental pilot and add-on therapy controlled with a placebo for 3 months. The case group received 200 mg of oral NAC three times a day. In contrast, the control group had a placebo in the same way. From the 2021 fall to the summer of 2022, 38 CF patients referred to Imam Hossein Children's Hospital Clinic were finally examined. They were clinically stable with a forced expiratory volume in the first second (FEV1) level of more than 50% and no history of underlying cardiovascular and renal diseases.

FINDINGS: The differences between the groups were not significant. In the placebo group, key measures remained unchanged, whereas the NAC group had an improvement in the CF Questionnaire-Revised score but no notable changes in other indices. Overall, comparisons of forced vital capacity (FVC) between the groups showed no variation.

CONCLUSION: The indicators of FEV1, FVC, FEV1/FVC, forced expiratory flow between 25% and 75% of vital capacity, and the quality of life of the case group were not significantly different from those of the placebo group, and no significant differences were observed between this medicine and placebo.},
}

@article {pmid40275970,
year = {2024},
author = {Shabani, AM and Alikhani, A and Heydari, F and Hosseinnataj, A and Sohrabi, M and Ramezaninejad, S and Ala, S and Kasgari, HA},
title = {Evaluation of the Effect of N-acetylcysteine in the Prevention of Colistin Nephrotoxicity in Critically Ill Patients: A Randomized Controlled Trial.},
journal = {Journal of research in pharmacy practice},
volume = {13},
number = {3},
pages = {85-91},
pmid = {40275970},
issn = {2319-9644},
abstract = {OBJECTIVE: The present study aimed to evaluate the efficacy of N-acetylcysteine (NAC) in preventing nephrotoxicity in critically ill patients receiving colistin.

METHODS: In a randomized, controlled clinical trial, eligible participants receiving colistin were divided into two groups: the drug group (n = 24) and the control group (n = 24). In the drug group, 2 g of NAC was administered intravenously daily for 5 days, simultaneously with colistin. The patients in the control group received only colistin. Serum creatinine (SCr), blood urea nitrogen (BUN), and creatinine clearance (CrCl) at baseline and on each day, and the number of cases of acute kidney injury during the study were recorded. Urinary N-acetyl-beta-D-glucosaminidase (NAG) was determined before the start of treatment and on day 5. The study outcomes were the mortality rate, length of intensive care unit (ICU) stay, and NAG levels. Finally, the values were compared between the groups.

FINDINGS: It was found that the 28-day mortality rate (P = 0.540) and length of ICU stay (P = 0.699) were not significantly improved by coadministration of intravenous N-acetylcysteine with colistin. SCr and BUN showed no significant reduction, and there were no changes in CrCl at the end of treatment. The changes in urinary NAG levels did not differ significantly between the two groups. There was also no difference in the stages of the RIFLE criteria (P = 0.641), and most patients were in the normal stage (58.3%).

CONCLUSION: Concomitant administration of intravenous NAC at a dose of 2 g daily does not prevent colistin-induced nephrotoxicity, 28-day mortality, and length of ICU stay in critically ill patients.},
}

@article {pmid40269590,
year = {2025},
author = {Liu, N and Liu, Y and Wang, X and Liu, M and Wang, Y and Feng, C and Piao, M},
title = {N-Acety-L-Cysteine Alleviates Isoflurane-Triggered Neuronal Cell Parthanatos by Suppressing Reactive Oxygen Species Accumulation Through the Induction of c-Jun N-Terminal Kinase Signaling Pathway Inhibition.},
journal = {Journal of biochemical and molecular toxicology},
volume = {39},
number = {5},
pages = {e70268},
pmid = {40269590},
issn = {1099-0461},
support = {//This investigation was supported by grants from the National Natural Science Foundation of China (Grant No. 81771141 and 82471221 to C. F.) and the Science and Technology Development Project of Jilin Province (Grant No. 20210101304JC to C. F.)./ ; },
mesh = {Animals ; *Isoflurane/adverse effects/pharmacology ; *Reactive Oxygen Species/metabolism ; Rats ; *Neurons/metabolism/drug effects/pathology ; *Acetylcysteine/pharmacology ; *JNK Mitogen-Activated Protein Kinases/metabolism ; *MAP Kinase Signaling System/drug effects ; Humans ; Hippocampus/metabolism/pathology ; *Parthanatos/drug effects ; *Anesthetics, Inhalation/adverse effects ; Rats, Sprague-Dawley ; Cell Line, Tumor ; Oxidative Stress/drug effects ; },
abstract = {In recent years, the potential neurotoxicity of inhaled anesthetics on the developing brain has increasingly garnered attention, yet its mechanism remains unclear. Parthanatos is a newly discovered form of programmed cell death dependent on PARP-1, and it is believed to be closely associated with cellular oxidative stress response. However, it is still to be proven whether isoflurane, a commonly used clinical anesthetic, can induce parthanatos in developing brain neurons and whether it activates the oxidative stress signaling pathway in neuronal cells. In this study, we treated SH-SY5Y cells and rat hippocampus neuron cells (RN-h) with isoflurane, measured cell viability using the MTT assay, examined the activation of the parthanatos-related PARP-1/AIF/PAR signaling pathway using western blot analysis, detected the accumulation of ROS using DCFH-DA, detected mitochondrial membrane potential (Δψm) by a JC-1 assay, and assessed the activation of the oxidative stress-related JNK signaling pathway using western blot. In vivo, we examined the damaging effects of inhaled isoflurane on neonatal rat hippocampal neurons using HE staining. The results showed that 2% and 4% concentrations of isoflurane significantly inhibited cell survival and upregulated the expression levels of PARP-1, AIF, and PAR in both types of neuronal cells. Moreover, isoflurane significantly enhanced ROS levels and decreased Δψm, and activated the JNK signaling pathway in both cell types. Importantly, we found that pretreatment with N-Acetylcysteine (NAC) could inhibit isoflurane-induced parthanatos and the accumulation of ROS in cells, as well as the activation of the JNK pathway. The experimental results in neonatal rats also demonstrated that isoflurane led to significant neuronal death in the hippocampal CA1 region. However, pretreatment with NAC significantly increased the survival rate of pyramidal neurons in this region. In summary, through our experiments, we confirmed that isoflurane can induce parthanatos in neuronal cells, and NAC can decrease ROS accumulation in neuronal cells and thus mitigate the damage isoflurane causes to neuronal cells.},
}

Animals
*Isoflurane/adverse effects/pharmacology
*Reactive Oxygen Species/metabolism
Rats
*Neurons/metabolism/drug effects/pathology
*Acetylcysteine/pharmacology
*JNK Mitogen-Activated Protein Kinases/metabolism
*MAP Kinase Signaling System/drug effects
Humans
Hippocampus/metabolism/pathology
*Parthanatos/drug effects
*Anesthetics, Inhalation/adverse effects
Rats, Sprague-Dawley
Cell Line, Tumor
Oxidative Stress/drug effects

@article {pmid40269151,
year = {2025},
author = {Liu, F and Lv, R and Qiao, X and Lv, G and Yuan, H and Han, J and Wang, X and Wan, J and Wang, M},
title = {Salinomycin and oxaliplatin synergistically enhances cytotoxic effect on human colorectal cancer cells in vitro and in vivo.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {14056},
pmid = {40269151},
issn = {2045-2322},
support = {SDYWZGKCJHLH2023095//Shandong Province Medical Staff Science and Technology Innovation Plan Project/ ; 2020NS160 and 2022NS319//Taian science and technology innovation and development project/ ; 2020NS160 and 2022NS319//Taian science and technology innovation and development project/ ; 2022MPM03//Nursery Project of the Affiliated Taian City Central Hospital of Qingdao University/ ; ZR2020MH239//Natural Science Foundation of Shandong Province, China/ ; },
mesh = {*Oxaliplatin/pharmacology ; Humans ; *Colorectal Neoplasms/drug therapy/metabolism/pathology ; *Pyrans/pharmacology/administration & dosage ; Drug Synergism ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Animals ; Cell Proliferation/drug effects ; Mice ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Cell Movement/drug effects ; *Antineoplastic Agents/pharmacology ; *Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Mice, Nude ; Polyether Polyketides ; },
abstract = {Oxaliplatin (OXA) is widely used for colorectal cancer (CRC) as a first-line chemotherapy. However, drug resistance and peripheral neurotoxicity prevail in colorectal cancer therapy. Salinomycin (SAL) makes cancer cells sensitive to ionizing radiation and chemotherapeutic drugs. Chemotherapy regimens that combine more than two drugs can improve the outcome of patients. In the present study, we detected apoptosis and mitochondrial function in CRC cells through MTT assays, Annexin V-FITC/PI staining, colony-forming assays, intracellular reactive oxygen species (ROS) measurements, western blotting and so on. We used CompuSyn software to calculate combination index (CI). The effect of SAL and OXA was synergistic. The combination treatment inhibited cell proliferation, migration and colony formation but increased the expression of proapoptotic proteins and promoted cell apoptosis of CRC cells. In vitro experiments demonstrated that the SAL and OXA cotreatment increased intracellular ROS levels in CRC cell lines, decreased the MMP and activated the mitogen-activated protein kinase (MAPK) pathway, thus inhibiting the proliferation of CRC cells and promoting the apoptosis of CRC cells. Pretreatment with N-acetylcysteine (NAC) reversed this effect. Cotreatment with SAL and OXA increases the apoptotic effects in OXA-treated CRC cell lines. In vivo, combined treatment of SAL and OXA markedly inhibited the tumor growth compared to either drug alone. SAL enhances OXA-induced antitumor effects in CRC both in vitro and in vivo by ROS-mediated mitochondrial apoptosis and activation of the MAPK pathway. These results may provide a rationale for combining SAL with OXA for CRC treatment.},
}

*Oxaliplatin/pharmacology
Humans
*Colorectal Neoplasms/drug therapy/metabolism/pathology
*Pyrans/pharmacology/administration & dosage
Drug Synergism
Apoptosis/drug effects
Reactive Oxygen Species/metabolism
Animals
Cell Proliferation/drug effects
Mice
Cell Line, Tumor
Xenograft Model Antitumor Assays
Cell Movement/drug effects
*Antineoplastic Agents/pharmacology
*Antineoplastic Combined Chemotherapy Protocols/pharmacology
Mice, Nude
Polyether Polyketides

@article {pmid40267072,
year = {2025},
author = {Oike, H and Yamasaki, K and Hashiguchi, K and Uehira, H},
title = {Evaluation of intake of aged garlic extract and organosulfur compounds on progressive hearing loss in DBA/2J mice.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0322105},
pmid = {40267072},
issn = {1932-6203},
mesh = {Animals ; *Garlic/chemistry ; Mice ; *Hearing Loss/drug therapy/physiopathology ; Mice, Inbred DBA ; *Plant Extracts/pharmacology/administration & dosage/chemistry/therapeutic use ; *Cysteine/analogs & derivatives/pharmacology/administration & dosage ; Male ; Evoked Potentials, Auditory, Brain Stem/drug effects ; Acetylcysteine/pharmacology ; *Sulfur Compounds/pharmacology/administration & dosage ; },
abstract = {Garlic is rich in organosulfur compounds with high antioxidant capacity and is known to have various health benefits. Aged garlic is a particularly effective source of these active compounds because it contains fewer toxic components. This study evaluated the effects of S-allyl cysteine (SAC), a major functional organosulfur compound in garlic, and aged garlic extract (AGE) on the suppression of progressive hearing loss. SAC and AGE were dissolved in drinking water at 1% (w/w) and administered to DBA/2J mice, a model of early progressive hearing loss, for 12 weeks, starting at 4 weeks of age. While the results revealed a trend toward weight loss in the SAC group, the weight of the AGE group was comparable to that of the control group, and no adverse events were observed in either group. The hearing ability of the mice was measured using auditory brainstem responses at 4, 8, 12, and 16 weeks of age. Hearing loss at 8 and 16 kHz progressed over the 12-week period, with neither sample inhibiting hearing loss. In contrast, another organosulfur compound, N-acetylcysteine (NAC), administered in 1% w/w drinking water and evaluated for hearing loss over time, significantly suppressed hearing loss progression in DBA/2J mice. These results indicate that the NAC and SAC differ in their ability to prevent hearing loss and demonstrate that the inhibitory effects of functional food components on hearing loss can be evaluated over a short period in DBA/2J mice.},
}

Animals
*Garlic/chemistry
Mice
*Hearing Loss/drug therapy/physiopathology
Mice, Inbred DBA
*Plant Extracts/pharmacology/administration & dosage/chemistry/therapeutic use
*Cysteine/analogs & derivatives/pharmacology/administration & dosage
Male
Evoked Potentials, Auditory, Brain Stem/drug effects
Acetylcysteine/pharmacology
*Sulfur Compounds/pharmacology/administration & dosage

@article {pmid40266430,
year = {2025},
author = {Chen, KL and Lu, HI and Yen, CY and Chen, CY and Chien, TM and Jeng, JH and Chen, BH and Chang, HW},
title = {Antioral cancer effects of ginger derivative 3-HDM exert oxidative stress-associated apoptosis and DNA damage.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {414},
pmid = {40266430},
issn = {1573-4978},
support = {112CM-KMU-05//Chimei-KMU jointed project/ ; MOST 111-2320-B-037-015-MY3//Ministry of Science and Technology, Taiwan/ ; KMU-TC113A04//Kaohsiung Medical University Research Center/ ; KMU-DK(A)113003 and KMU-TB114009//Kaohsiung Medical University/ ; },
mesh = {Humans ; *Oxidative Stress/drug effects ; *Apoptosis/drug effects ; *Zingiber officinale/chemistry ; *DNA Damage/drug effects ; *Mouth Neoplasms/drug therapy/metabolism/genetics/pathology ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism ; Cell Survival/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Cell Proliferation/drug effects ; Acetylcysteine/pharmacology ; },
abstract = {BACKGROUND: 3-Hydroxy-1-(3',5'-dimethoxy-4'-hydroxy-phenyl)-hexan-5-one (3-HDM), a novel ginger Zingiber officinale-derived compound, lacks anti-cancer investigation, especially for oral cancer. This study addresses the antioral function and mechanism of 3-HDM against oral cancer cells (Ca9-22 and CAL 27).

METHOD: MTS, flow cytometry, and western blotting were used to determine cell viability and antioral function and mechanism.

RESULTS: 3-HDM inhibits oral cancer cell viability without normal cell (S-G) toxicity. This selective antiproliferation relies on oxidative stress validated by N-acetylcysteine (NAC), a reactive oxygen species (ROS) remover. 3-HDM upregulates subG1 and annexin V proportions, enhances caspases 3 and 8 activation to a greater extent in oral cancer than in normal cells, reverted by NAC. This process demonstrates the ROS-dependent selective apoptotic character of 3-HDM. 3-HDM also upregulates more ROS and mitochondrial superoxide and downregulates the mitochondrial membrane potential and glutathione in oral cancer than in normal cells in a ROS-dependent manner. Moreover, 3-HDM suppresses antioxidant signaling mRNA expressions such as NFE2L2, NQO1, and TXN and inhibits NFE2L2 phosphorylation in oral cancer cells compared to normal cells. NAC also downregulates the 3-HDM-induced γH2AX and 8-hydroxy-2-deoxyguanosine DNA damage markers.

CONCLUSION: 3-HDM shows selective antioral cancer effects and mechanisms without toxicity to normal cells via oxidative stress regulation.},
}

Humans
*Oxidative Stress/drug effects
*Apoptosis/drug effects
*Zingiber officinale/chemistry
*DNA Damage/drug effects
*Mouth Neoplasms/drug therapy/metabolism/genetics/pathology
Cell Line, Tumor
Reactive Oxygen Species/metabolism
Cell Survival/drug effects
Membrane Potential, Mitochondrial/drug effects
Cell Proliferation/drug effects
Acetylcysteine/pharmacology

@article {pmid40262667,
year = {2025},
author = {Liu, R and Dai, L and Jia, S and Geng, S and Niu, Y and Chen, J and Dong, C and Li, C and Shi, Y and Wang, X and Zhang, J and Zhao, N and Gao, Z and Yang, X and Gao, S},
title = {Fut8 regulated Unc5b hyperfucosylation reduces macrophage emigration and accelerates atherosclerosis development via the ferroptosis pathway.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2025.04.025},
pmid = {40262667},
issn = {1873-4596},
abstract = {The accumulation of foam cells in the arterial walls is a defining characteristic of atherosclerosis. Enhancing their migration from plaques may represent a key strategy for slowing disease progression. Recent studies suggest that fucosyltransferase 8 (Fut8) impairs macrophage migration from the intima by modifying the Unc5b membrane receptor, thereby influencing the development of atherosclerosis. This study investigated the roles of Fut8 and Unc5b in foam cell migration using ApoE[-/-] mouse and foam cell models, employing techniques such as western blotting, mitochondrial function assays, wound healing experiments, and immunofluorescence staining. The findings indicate that Fut8 upregulation increases P53 expression and reduces SLC7A11 and GPX4 levels, leading to altered intracellular concentrations of GSH and Fe[2+], impaired mitochondrial function, and reduced migration capacity, all of which promote atherosclerosis. These mechanisms are closely associated with ferroptosis. Intervention with N-acetylcysteine (NAC) and buthionine sulfoximine (BSO) demonstrated that NAC mitigates oxidative stress and migration inhibition,induced by oxidized low-density lipoprotein (ox-LDL). Additionally, inhibiting ferroptosis slowed the progression of atherosclerosis in ApoE[-/-] mice. Together, these results highlight that Fut8 exacerbates atherosclerosis through a P53/SLC7A11-mediated enhancement of ferroptosis in foam cells, offering a novel perspective on the pathophysiology of atherosclerosis.},
}

@article {pmid40257108,
year = {2025},
author = {He, W and Xu, L and Jiang, W and Yao, S and Fu, Y and Cheng, Z and Zhang, D and Huang, L},
title = {miR-223-3p Mitigates Mitochondrial Dysfunction and Cementoblast Apoptosis in Orthodontic Root Resorption via FoxO3.},
journal = {Journal of periodontal research},
volume = {},
number = {},
pages = {},
doi = {10.1111/jre.13384},
pmid = {40257108},
issn = {1600-0765},
support = {82170989//National Natural Science Foundation of China/ ; KQY202307//the Scientific Research and Innovation Project for Postgraduates of the Affiliated Stomatological Hospital of Chongqing Medical University/ ; CSTB2022NSCQ-MSX0794//Natural Science Foundation of Chongqing Municipality/ ; },
abstract = {AIM: The aim of this study was to elucidate the roles of miR-223-3p in orthodontically induced inflammatory root resorption (OIIRR).

METHODS: We used high-throughput miRNA sequencing and transcriptome sequencing to analyze the differentially expressed miRNAs and mRNAs in OCCM-30 cells under hypoxia. Real-time quantitative PCR (RT-qPCR) and Western blotting were used to assess the expression of genes and proteins related to apoptosis, oxidative stress, and mitochondrial dysfunction. Fluorescence staining was employed to detect changes in cellular ROS (reactive oxygen species), MMP (mitochondrial membrane potential), and mtROS (mitochondrial ROS) expression.

RESULTS: We found that miR-223-3p targeted FoxO3 to regulate apoptosis in cementoblasts under hypoxic conditions. Moreover, hypoxia-induced FoxO3 increased oxidative stress and induced mitochondrial dysfunction in cementoblasts, resulting in cell apoptosis. Administration of the ROS inhibitor NAC (N-acetyl cysteine) effectively reversed FoxO3-induced oxidative stress and mitochondrial dysfunction, thereby rescuing cell apoptosis.

CONCLUSIONS: miR-223-3p targets FoxO3 and regulates the apoptosis of cementoblasts by improving oxidative stress and mitochondrial dysfunction. These findings may offer new insights into the mechanism of OIIRR.},
}

@article {pmid40256695,
year = {2025},
author = {Narvekar, PS and Shivanand, S and Patil, S and Raikar, S and Mallick, A and Doddwad, PK},
title = {Dentinal tubule penetration of a silicone-based endodontic sealer following N-acetyl cysteine intracanal medicament removal using ultrasonic agitation and laser activated irrigation - An in vitro study.},
journal = {Journal of conservative dentistry and endodontics},
volume = {28},
number = {3},
pages = {231-236},
pmid = {40256695},
issn = {2950-4708},
abstract = {CONTEXT: The removal of intracanal medicament is essential for sealer penetration and the success of endodontic therapy.

AIMS: To evaluate and compare the dentinal tubule penetration of a silicone-based endodontic sealer following N-acetyl cysteine (NAC) intracanal medicament removal using ultrasonic agitation and laser-activated irrigation.

MATERIALS AND METHODS: Eighty-one extracted single-rooted mandibular premolars were decoronated and prepared with ProTaper Universal rotary files up to MAF F3. To prepare medicament, NAC powder was mixed with propylene glycol in the ratio of 1:1, placed using a size #30 Lentulospiral, and specimens stored in an incubator for 14 days. The specimens were then instrumented with #30 Hedström and divided into three groups according to final irrigant activation techniques: Group I: Diode laser activation, Group II: Passive Ultrasonic agitation, Group III: No agitation (positive control). Canals were obturated with GuttaFlow bioseal sealer mixed with 0.1% Rhodamine B dye and gutta-percha cones and incubated for 7 days. The specimens were sectioned horizontally to obtain 1 mm thick sections from 2, 5, and 8 mm from the apex. Sections were examined under Confocal Laser Scanning Microscope to measure the depth of sealer penetration (in µm).

STATISTICAL ANALYSIS: One-way analysis of variance and Tukeys multiple post hoc test.

RESULTS: The highest mean depth of penetration of 728.52 µm was seen with Group I, followed by Group II and least was seen in Group III.

CONCLUSIONS: Diode laser activation group was most effective in the removal of NAC intracanal medicament from all the three regions of the root canal.},
}

@article {pmid40253238,
year = {2025},
author = {Zhou, Q and Lin, J and Li, Q},
title = {Study of high-strength, low-shrinkage dental resin composites with bifunctional polysilsesquioxane.},
journal = {Dental materials : official publication of the Academy of Dental Materials},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.dental.2025.03.012},
pmid = {40253238},
issn = {1879-0097},
abstract = {OBJECTIVES: The aim of this study was to develop a new composite resin to solve the problem of volume shrinkage of conventional dental restorative composite resins during the curing process in order to improve their mechanical properties and reduce the risk of restoration failure.

METHODS: We synthesized the mercapto-alkenyl click chemical reaction product (MN-POSS) of acrylate-based POSS (MAP-POSS) with N-Acetylcysteine (NAC) using a bifunctional polysilsesquioxane modification technique and improved its dispersion in the resin matrix by physicochemical methods. In addition, methacrylate-based epoxy POSS (ME-POSS) was further synthesized and used to modify acrylate dental resins to form a free radical-cation hybrid light-curing system.

RESULTS: The results showed that the composites modified with MN-POSS significantly improved mechanical strength, while the application of ME-POSS effectively reduced polymerization shrinkage, improved the water absorption and dissolution properties of the materials, and enhanced mechanical properties and hardness. This study provides new ideas and material solutions to improve the performance of dental restorative materials.

SIGNIFICANCE: Both of these improved solutions demonstrate the potential of bifunctional POSS as a modified filler, providing new ideas and methods for the design of future dental restorative materials.},
}

@article {pmid40252905,
year = {2025},
author = {Ricardi, LL and Zecchinati, F and Perdomo, VG and Basiglio, CL and García, F and Arana, MR and Villanueva, SSM},
title = {Oxidative stress promotes post-translational down-regulation of MRP2 in Caco-2 Cells: involvement of proteasomal degradation and toxicological implications.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {},
number = {},
pages = {115459},
doi = {10.1016/j.fct.2025.115459},
pmid = {40252905},
issn = {1873-6351},
abstract = {The intestinal tract is highly susceptible to oxidative stress (OS), which impairs gut barrier function. Multidrug Resistance-Associated Protein 2 (MRP2) is a key efflux pump in the intestinal transcellular barrier, regulating toxicant and drug disposition. We here evaluated the effects of OS on MRP2 in Caco-2 cells treated with tert-butyl hydroperoxide (TBH). After 24 h, TBH 250 μM increased ROS production and lipid peroxidation while decreasing GSH content and SOD activity, confirming OS induction. Under these conditions, total MRP2 protein levels decreased, while P-gp levels remained unchanged. Correspondingly, MRP2 efflux activity decreased, impairing barrier function against ochratoxin A (OTA), a substrate of MRP2, and exacerbating OTA toxicity. Localization analysis revealed reduced apical MRP2 signal in TBH 250 group, with unchanged mRNA levels, indicating post-transcriptional regulation. Mechanistically, TBH induced rapid MRP2 internalization (30 min), mediated by cPKC and clathrin, without microtubule involvement, followed by proteasomal degradation at 24 h. Both processes were dependent on GSH depletion, as treatment with N-Acetyl-L-Cysteine (NAC) restored GSH levels, MRP2 localization, and activity. We provide here the first evidence that human intestinal MRP2 is post-translationally downregulated under specific OS conditions, highlighting its potential role in exacerbating xenobiotic absorption and toxicity in OS-related human diseases.},
}

@article {pmid40251236,
year = {2025},
author = {Poojary, KK and Kunhiraman, JP and Madhvacharya, VV and Kumari, S and Krishna, N and S, SP and K, RG and Mutalik, S and Ghani, NK and Kabekkodu, SP and Prasad, TSK and Adiga, SK and Kalthur, G},
title = {Bromodomain and extraterminal protein inhibitor JQ1 induces maturation arrest and disrupts the cytoplasmic organization in mouse oocytes under in vitro conditions.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13448},
pmid = {40251236},
issn = {2045-2322},
mesh = {Animals ; *Oocytes/drug effects/metabolism/cytology ; Mice ; *Azepines/pharmacology ; *Triazoles/pharmacology ; Female ; Endoplasmic Reticulum Chaperone BiP ; *Cytoplasm/drug effects/metabolism ; In Vitro Oocyte Maturation Techniques ; Oxidative Stress/drug effects ; Oogenesis/drug effects ; },
abstract = {JQ1, a small cell-permeable molecule is known for its potent inhibitory action on bromodomain and extraterminal (BET) proteins. Although earlier studies have shown its inhibitory effect on male gametogenesis, limited information is available about its influence on oocyte development. Since BET genes are known to exhibit regulatory functions on oocyte development and maturation, the present study aimed to investigate the effect of JQ1 on oocyte developmental competence under in vitro conditions. Germinal vesicle (GV) stage oocytes were collected from adult Swiss albino mice and subjected to in vitro maturation (IVM) in the presence of various concentrations of JQ1 (25, 50, and 100 μM). The metaphase II (MII) stage oocytes were assessed for cytoplasmic organization and functional competence at 24 h after IVM. A significant decrease in nuclear maturation (at 50 and 100 μM), symmetric cytokinesis, altered distribution of mitochondria and cortical granules, poorly organized actin and meiotic spindle, misaligned chromosomes, and elevated endoplasmic reticulum (ER) stress and oxidative stress was observed in JQ1-exposed oocytes. Presence of N-acetyl cysteine (NAC), in IVM medium resulted in significant reduction in JQ1-induced oxidative stress and symmetric cytokinesis. Administration of JQ1 (50 mg/kg, intra peritoneal) to adult Swiss albino mice primed with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) did not affect the ovulation. However, a high degree of oocyte degeneration, elevated intracellular reactive oxygen species (ROS), and GRP78 expression was observed in JQ1-administered mice. In conclusion, our study reveals that BET inhibitor JQ1 has detrimental effects on oocyte function and development.},
}

Animals
*Oocytes/drug effects/metabolism/cytology
Mice
*Azepines/pharmacology
*Triazoles/pharmacology
Female
Endoplasmic Reticulum Chaperone BiP
*Cytoplasm/drug effects/metabolism
In Vitro Oocyte Maturation Techniques
Oxidative Stress/drug effects
Oogenesis/drug effects

@article {pmid40243461,
year = {2025},
author = {Bilski, R and Nuszkiewicz, J},
title = {Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
pmid = {40243461},
issn = {1422-0067},
mesh = {Humans ; *Arthritis, Rheumatoid/drug therapy/metabolism ; *Oxidative Stress/drug effects ; *Antioxidants/therapeutic use/pharmacology ; Animals ; Reactive Oxygen Species/metabolism ; Antirheumatic Agents/therapeutic use/pharmacology ; Treatment Outcome ; },
abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation and progressive joint destruction. Recent data underscore oxidative stress as a primary factor in the pathophysiology of rheumatoid arthritis, intensifying inflammatory processes and tissue damage via the overproduction of reactive oxygen species (ROS) and compromised antioxidant defenses. Current therapies, including disease-modifying antirheumatic drugs (DMARDs), primarily target immune dysregulation but fail to address oxidative stress, necessitating novel adjunctive treatment strategies. This review explores the potential of antioxidant-based therapies as complementary approaches to RA management. Natural compounds such as curcumin, resveratrol, sulforaphane, and propolis exhibit strong anti-inflammatory and antioxidative properties by modulating redox-sensitive pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase (HO-1). N-acetylcysteine (NAC) replenishes intracellular glutathione, enhancing cellular resilience against oxidative stress. Additionally, molecular hydrogen (H2) selectively neutralizes harmful ROS, reducing oxidative damage and inflammation. The role of vitamin supplementation (D, B12, C, and K) in regulating immune responses and protecting joint structures is also discussed. This review aims to evaluate the efficacy and potential clinical applications of antioxidant therapies in RA, emphasizing their role in mitigating oxidative damage and improving treatment outcomes. While preliminary findings are promising, further clinical trials are needed to establish standardized dosing, long-term safety, and their integration into current RA treatment protocols.},
}

Humans
*Arthritis, Rheumatoid/drug therapy/metabolism
*Oxidative Stress/drug effects
*Antioxidants/therapeutic use/pharmacology
Animals
Reactive Oxygen Species/metabolism
Antirheumatic Agents/therapeutic use/pharmacology
Treatment Outcome

@article {pmid40243112,
year = {2025},
author = {She, Z and Zeng, F and Wu, S},
title = {A zwitterionic chromophore as both a biomarker-activatable optical imaging probe and a therapeutic agent for the detection and treatment of acute lung injury with bacterial infection.},
journal = {Biomaterials science},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5bm00419e},
pmid = {40243112},
issn = {2047-4849},
abstract = {Acute lung injury (ALI), often complicated by bacterial infection, poses significant challenges in diagnosis and treatment. Nitric oxide (NO) plays a key role in the pathophysiology of ALI, making it an ideal biomarker for early detection. In this study, we developed a zwitterionic chromophore, ZW-N, designed as both a biomarker-activatable imaging probe and a therapeutic agent for ALI with bacterial infection. The chromophore ZW-N integrates quaternary ammonium groups for antimicrobial activity and zwitterionic sulfonate groups to enhance biocompatibility and water solubility. Built on a flexible propanyl linker that couples two heptamethine cyanine dyes, ZW-N enables biomarker-responsive dual-modal imaging via optoacoustic (OA) imaging and near-infrared second-window (NIR-II) fluorescence imaging. Moreover, the chromophore ZW-N demonstrates therapeutic efficacy when combined with the clinically used antioxidant N-acetylcysteine (NAC) to treat ALI with bacterial infection. This dual-functional chromophore offers a promising platform for non-invasive, real-time monitoring of ALI, providing significant potential for improved detection and a more effective treatment strategy.},
}

@article {pmid40240934,
year = {2025},
author = {Kim, JH and Lee, JH and Koo, YJ and Song, JW},
title = {N-actylcysteine inhibits diethyl phthalate-induced inflammation via JNK and STAT pathway in RAW264.7 macrophages.},
journal = {BMC molecular and cell biology},
volume = {26},
number = {1},
pages = {12},
pmid = {40240934},
issn = {2661-8850},
support = {2022R1I1A1A01068466//National Research Foundation of Korea/ ; 2022R1A2C1011500//National Research Foundation of Korea/ ; 2022R1F1A1075191//National Research Foundation of Korea/ ; },
mesh = {Animals ; Mice ; RAW 264.7 Cells ; *Phthalic Acids/toxicity ; *Macrophages/drug effects/metabolism ; *Inflammation/chemically induced/metabolism/drug therapy ; Reactive Oxygen Species/metabolism ; Cyclooxygenase 2/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Glutathione/metabolism ; Dinoprostone/metabolism ; *MAP Kinase Signaling System/drug effects ; Nitric Oxide/metabolism ; Signal Transduction/drug effects ; *STAT Transcription Factors/metabolism ; STAT3 Transcription Factor/metabolism ; *Acetylcysteine/pharmacology ; },
abstract = {BACKGROUND: Phthalates are plasticizers that cause inflammation in several cell types and adversely affect the health of humans and animals. Nacetylcysteine (NAC) has been shown to exert antioxidant effects in various diseases. However, the effect of NAC on diethyl phthalate (DEP)-induced toxicity in macrophages has not yet been elucidated. In this study, we investigated the effect and underlying mechanisms of NAC on DEP-induced inflammation in RAW264.7 macrophages. RAW264.7 macrophages were pretreated with NAC for 2 h followed by exposure to DEP. We investigated the effect of NAC on NO, reactive oxygen species (ROS), prostaglandin E2 (PGE2), and glutathione (GSH) levels following DEP exposure. In addition, pathway-related genes including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription (STAT) were evaluated using western blot.

RESULTS: Treatment with 100 and 300 µM DEHP, DBP, and DEP significantly increased the protein levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) compared with those in the control group. However, NAC pretreatment downregulated the levels of NO, PGE2, and ROS, elevated GSH levels, and suppressed the mRNA levels of inflammatory cytokines such as interleukin (IL)-1β, IL-6, COX-2, and iNOS compared with those in the DEP-treated group. In addition, NAC significantly reduced the levels of p-JNK and p-STAT1/3 in RAW264.7 macrophages treated with DEP.

CONCLUSIONS: NAC pretreatment inhibits DEP-induced inflammation via the MAPK/JNK and STAT1/3 pathways in macrophages.},
}

Animals
Mice
RAW 264.7 Cells
*Phthalic Acids/toxicity
*Macrophages/drug effects/metabolism
*Inflammation/chemically induced/metabolism/drug therapy
Reactive Oxygen Species/metabolism
Cyclooxygenase 2/metabolism
Nitric Oxide Synthase Type II/metabolism
Glutathione/metabolism
Dinoprostone/metabolism
*MAP Kinase Signaling System/drug effects
Nitric Oxide/metabolism
Signal Transduction/drug effects
*STAT Transcription Factors/metabolism
STAT3 Transcription Factor/metabolism
*Acetylcysteine/pharmacology

@article {pmid40236464,
year = {2024},
author = {Wu, J and Maller, B and Kaul, R and Galabow, A and Bryan, A and Neuwelt, A},
title = {High-Dose Acetaminophen as a Treatment for Cancer.},
journal = {Livers},
volume = {4},
number = {1},
pages = {84-91},
pmid = {40236464},
issn = {2673-4389},
support = {IK2 BX004914/BX/BLRD VA/United States ; },
abstract = {The use of high-dose acetaminophen (AAP) with n-acetylcysteine (NAC) rescue was studied as an anti-cancer treatment in phase I trials with promising signals of anti-tumor efficacy. Correlative analysis suggested that AAP has a free-radical-independent mechanism of anti-tumor activity-in contrast to the well-established mechanism of AAP hepatotoxicity. Subsequent "reverse translational" studies in the pre-clinical setting have identified novel mechanisms of action of high-dose AAP, including modulation of JAK-STAT signaling in both the tumor cell and the tumor immune microenvironment. Importantly, these effects are free-radical-independent and not reversed by concurrent administration of the established AAP rescue agents fomepizole and NAC. By administering high-dose AAP concurrently with fomepizole and NAC, 100-fold higher AAP levels than those of standard dosing can be achieved in mice without detected toxicity and with substantial anti-tumor efficacy against commonly used mouse models of lung and breast cancer that are resistant to standard first-line anti-cancer therapies. With these recent advances, additional clinical trials of high-dose AAP with concurrent NAC and fomepizole-based rescue are warranted.},
}

@article {pmid40235406,
year = {2025},
author = {Yildirim, B and Erturk, C and Buyukdogan, H and Saritas, TB and Yildirim Erdogan, N and Ertem, F},
title = {Effect of N-acetylcysteine on fracture healing in rat femoral diaphysis: A histopathological, radiological, and biomechanical analysis.},
journal = {Joint diseases and related surgery},
volume = {36},
number = {2},
pages = {283-292},
doi = {10.52312/jdrs.2025.1975},
pmid = {40235406},
issn = {2687-4792},
mesh = {Animals ; *Acetylcysteine/pharmacology ; Male ; Rats, Wistar ; *Fracture Healing/drug effects ; *Femoral Fractures/diagnostic imaging/pathology/physiopathology/drug therapy/surgery ; Rats ; Diaphyses/diagnostic imaging/drug effects/pathology/injuries ; Biomechanical Phenomena ; Disease Models, Animal ; *Antioxidants/pharmacology ; *Femur/diagnostic imaging/drug effects/pathology/physiopathology ; Radiography ; },
abstract = {OBJECTIVES: The aim of this study was to examine the effect of N-acetylcysteine (NAC), which has antioxidant properties, on healing in a rat femoral diaphysis fracture model.

MATERIALS AND METHODS: Twenty-four male Wistar-Hannover rats were randomly divided into two groups: experimental (n=12) and control groups (n=12). An open femur fracture model (osteotomy) was applied to the right femora of both groups. Fixation was performed with Kirschner wire. While intraperitoneal NAC treatment was given to the experimental group for 21 days after surgery, an equal volume of intraperitoneal saline injection was administered to the control group. At the end of this period, the femurs obtained from the sacrificed animals were examined histopathologically, radiologically, and biomechanically. Huo scoring was used for histopathological examination. The samples were examined radiologically according to the Radiographic Union Scale in Tibial Fractures (RUST) scoring system. The three-point bending test was used for the biomechanical examination.

RESULTS: According to the third-week results, NAC could histopathologically contribute positively to fracture healing in rats (p=0.003 and p<0.05, respectively). Considering radiological and biomechanical parameters, no significant difference was observed between the groups in terms of healing (p>0.05). However, a positive significant correlation (67.7%) was found between histopathological results and radiological findings (p=0.016 and p<0.05, respectively).

CONCLUSION: Our study results indicate that NAC may have a histopathologically positive effect on the healing process in rat traumatic fractures. Based on these findings, NAC preparations may be used as a supportive agent in the treatment of fractures. Further clinical studies are needed.},
}

Animals
*Acetylcysteine/pharmacology
Male
Rats, Wistar
*Fracture Healing/drug effects
*Femoral Fractures/diagnostic imaging/pathology/physiopathology/drug therapy/surgery
Rats
Diaphyses/diagnostic imaging/drug effects/pathology/injuries
Biomechanical Phenomena
Disease Models, Animal
*Antioxidants/pharmacology
*Femur/diagnostic imaging/drug effects/pathology/physiopathology
Radiography

@article {pmid40229128,
year = {2025},
author = {Li, P and Meng, X and Lu, T and Sun, C and Song, G},
title = {Synergistic Effect of ROS and p38 MAPK in Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.4789},
pmid = {40229128},
issn = {1099-1263},
support = {82460651//National Natural Science Foundation of China/ ; 21966027//National Natural Science Foundation of China/ ; 2023AB049//Science and Technology Planning Project of Xinjiang Production and Construction Corps/ ; },
abstract = {The adverse effects of titanium dioxide nanoparticles (TiO2 NPs) on the integrity of the blood-testis barrier (BTB) are widely recognized. However, the underlying mechanisms remain incompletely understood. The integrity of the BTB is imperative for the preservation of male reproductive health. TM4 cells, which are major component of the BTB, play a critical role in its integrity. The apoptosis of TM4 cells is closely associated with the disruption of the BTB. Therefore, we selected TM4 cells as experimental models to investigate the apoptosis induced by TiO2 NPs and the underlying mechanisms. Cell viability, excessive production of reactive oxygen species (ROS), activation of p38 mitogen-activated protein kinase (MAPK) pathway, and apoptosis-related protein expression levels were determined under various concentrations (50, 100, 150, and 200 μg/mL) of TiO2 NPs exposure. The results indicate that TiO2 NPs induced the overproduction of ROS and activated the p38 MAPK signaling pathway, which subsequently led to apoptosis. The ROS scavenger N-acetylcysteine (NAC) was able to suppress the activation of p38 MAPK pathway induced by TiO2 NPs, while the p38 MAPK inhibitor SB203580 mitigated TiO2 NPs-induced ROS overproduction and subsequent apoptosis, suggesting an interplay between ROS overproduction and p38 MAPK pathway activation. In summary, TiO2 NPs induced mitochondrial apoptosis via the ROS-p38 MAPK axis. A positive feedback regulatory mechanism exists between the two processes, promoting apoptosis in TM4 cells through a synergistic effect.},
}

@article {pmid40227392,
year = {2025},
author = {Amador-Martínez, I and Aparicio-Trejo, OE and Aranda-Rivera, AK and Bernabe-Yepes, B and Medina-Campos, ON and Tapia, E and Cortés-González, CC and Silva-Palacios, A and Roldán, FJ and León-Contreras, JC and Hernández-Pando, R and Saavedra, E and Gonzaga-Sánchez, JG and Ceja-Galicia, ZA and Sánchez-Lozada, LG and Pedraza-Chaverri, J},
title = {Effect of N-Acetylcysteine in Mitochondrial Function, Redox Signaling, and Sirtuin 3 Levels in the Heart During Cardiorenal Syndrome Type 4 Development.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {3},
pages = {},
pmid = {40227392},
issn = {2076-3921},
support = {CBF2023-2024-190//CONAHCYT/ ; IN200922 and IN202725//PAPIIT-UNAM/ ; 21-1250//Instituto Nacional de Cardiología Ignacio Chávez/ ; },
abstract = {Type 4 cardiorenal syndrome (CRS-4) is a pathology in which chronic kidney disease (CKD) triggers the development of cardiovascular disease. CKD pathophysiology produces alterations that can affect the bioenergetics of heart mitochondria, causing oxidative stress and reducing antioxidant glutathione (GSH) levels. GSH depletion alters protein function by affecting post-translational modifications such as S-glutathionylation (RS-SG), exacerbating oxidative stress, and mitochondrial dysfunction. On the other hand, N-acetylcysteine (NAC) is an antioxidant GSH precursor that modulates oxidative stress and RS-SG. Moreover, recent studies have found that NAC can activate the Sirtuin 3 (SIRT3) deacetylase in diseases. However, the role of NAC and its effects on mitochondrial function, redox signaling, and SIRT3 modifications in the heart during CRS-4 have not been studied. This study aimed to investigate the role of NAC in mitochondrial function, redox signaling, and SIRT3 in the hearts of animals with CRS-4 at two months of follow-up. Our results showed that the oral administration of NAC (600 mg/kg/day) improved blood pressure and reduced cardiac fibrosis. NACs' protective effect was associated with preserving cardiac mitochondrial bioenergetics and decreasing these organelles' hydrogen peroxide (H2O2) production. Additionally, NAC increased GSH levels in heart mitochondria and regulated the redox state, which coincided with an increase in nicotinamide adenine dinucleotide oxidized (NAD[+]) levels and a decrease in mitochondrial acetylated lysines. Finally, NAC increased SIRT3 levels and the activity of superoxide dismutase 2 (SOD-2) in the heart. Thus, treatment with NAC decreases mitochondrial alterations, restores redox signaling, and decreases SIRT3 disturbances during CRS-4 through an antioxidant defense mechanism.},
}

@article {pmid40220949,
year = {2025},
author = {Sztolsztener, K and Michalak, D and Chabowski, A},
title = {N-acetylcysteine influence on PI3K/Akt/mTOR and sphingolipid pathways in rats with MASLD induced by HFD: a promising new therapeutic purpose.},
journal = {Molecular and cellular endocrinology},
volume = {603},
number = {},
pages = {112545},
doi = {10.1016/j.mce.2025.112545},
pmid = {40220949},
issn = {1872-8057},
abstract = {Sphingolipid and glucose metabolism play important roles in the induction and progression of severe liver disorders like metabolic dysfunction-associated steatotic liver disease (MASLD). The perturbation in sphingolipid formation may improve the liver structure and functioning and may constitute the potential therapeutic options for the development of simple steatosis and its progression to steatohepatitis. This study aims to assess the influence of N-acetylcysteine (NAC) on the sphingolipid and insulin signaling pathways in rats subjected to standard or high-fat diets. Sphingolipid level was measured using high-performance liquid chromatography (HPLC). A multiplex assay kit determined the level of phosphorylated form of proteins included in the PI3K/Akt/mTOR pathway. The immunoblotting estimated the expression of proteins from sphingolipid and insulin transduction pathways. A histological Oil red O staining was used to assess the hepatic accumulation of lipid droplets. Molecular docking was applied to showcase NAC interaction with PI3K/Akt/mTOR pathway proteins. NAC decreased dihydroceramide and ceramide levels and increased phosphorylation of sphingosine and sphinganine. This antioxidant also enhanced phosphorylated Akt, GSK3α/β, and P70 S6 kinase and decreased phosphorylated S6RP. In silico docking analysis of insulin signaling molecules evidenced the higher binding affinity of NAC with all tested proteins, i.e., IRS1, PTEN, Akt, GSK3α/β, P70 S6 kinase, and S6RP, suggesting a potential protective influence on insulin resistance development, which is one of the criteria for MASLD diagnosing. Based on these data, NAC improved the hepatic insulin sensitivity and sphingolipid synthesis and storage, improving and restoring glucose homeostasis.},
}

@article {pmid40220169,
year = {2025},
author = {Ciftel, E and Mercantepe, T and Ciftel, S and Karakas, SM and Aktepe, R and Yilmaz, A and Mercantepe, F},
title = {Somatostatin and N-acetylcysteine on testicular damage triggered by ischemia reperfusion: cellular protection and antioxidant effects.},
journal = {Hormones (Athens, Greece)},
volume = {},
number = {},
pages = {},
pmid = {40220169},
issn = {2520-8721},
abstract = {Ischemia-reperfusion (I/R) injury is a significant cause of testicular damage, leading to infertility and other reproductive dysfunctions. Antioxidant therapies have emerged as a potential intervention to mitigate oxidative stress and cellular damage. This study investigates the effects of somatostatin (SST) and N-acetylcysteine (NAC) on testicular damage induced by I/R, focusing on their antioxidant and cellular protective effects. Twenty-four male rats were divided into four groups, as follows: sham operated, I/R injury, I/R + somatostatin treatment, and I/R + NAC treatment. A testicular I/R injury was induced surgically, followed by either SST or NAC administration. Testicular tissues were assessed histopathologically using hematoxylin and eosin staining and employing Johnson's biopsy scoring. Immunohistochemical analyses were performed for caspase- 3, 8-hydroxy- 2'-deoxyguanosine (8-OHdG), testis-specific histone 2B, and testosterone to evaluate apoptosis, oxidative DNA damage, cellular proliferation, and steroidogenesis, respectively. Serum levels of testosterone and follicle-stimulating hormone (FSH) were measured by biochemical analysis. The results showed that both SST and NAC treatments significantly ameliorated histopathological damage and reduced the levels of caspase- 3 and 8-OHdG, indicating reduced apoptosis and oxidative DNA damage. Furthermore, increased testis-specific histone 2B positivity suggested enhanced cellular proliferation. Notably, administration of SST decreased testosterone positivity in the testis, whereas NAC treatment increased it. However, no significant differences in serum testosterone levels were observed between the NAC and SST groups. In addition, serum FSH levels of the I/R + SST group were found to be significantly higher than those of the control group. SST and NAC exhibit protective effects against testicular damage induced by I/R, as evidenced by their antioxidant and anti-apoptotic properties. The differential impact on testosterone positivity in the testis tissue highlights distinct underlying mechanisms, warranting further investigation. Despite these promising findings, the lack of significant changes in serum hormone levels calls for additional studies to fully elucidate the therapeutic potential and mechanistic pathways of SST and NAC in the context of testicular I/R injury.},
}

@article {pmid40218498,
year = {2025},
author = {Jensch, H and Setford, S and Thomé, N and Srikanthamoorthy, G and Weingärtner, L and Grady, M and Holt, E and Pfützner, A},
title = {Dynamic Interference Testing-Unexpected Results Obtained with the Abbott Libre 2 and Dexcom G6 Continuous Glucose Monitoring Devices.},
journal = {Sensors (Basel, Switzerland)},
volume = {25},
number = {7},
pages = {},
pmid = {40218498},
issn = {1424-8220},
support = {951933 (ForgetDiabetes)//European Union's Horizon 2020 research and innovation program/ ; Unrestricted grant//Lifescan Global Corp./ ; },
mesh = {*Blood Glucose Self-Monitoring/instrumentation/methods ; Humans ; *Blood Glucose/analysis ; *Biosensing Techniques/methods ; Continuous Glucose Monitoring ; },
abstract = {BACKGROUND: Sensors for continuous glucose monitoring (CGM) are now commonly used by people with type 1 and type 2 diabetes. However, the response of these devices to potentially interfering nutritional, pharmaceutical, or endogenous substances is barely explored. We previously developed an in vitro test method for continuous and dynamic CGM interference testing and herein explore the sensitivity of the Abbott Libre2 (L2) and Dexcom G6 (G6) sensors to a panel of 68 individual substances.

METHODS: In each interference experiment, L2 and G6 sensors were exposed in triplicate to substance gradients from zero to supraphysiological concentrations at a stable glucose concentration of 200 mg/dL. YSI Stat 2300 Plus was used as the glucose reference method. Interference was presumed if the CGM sensors showed a mean bias of at least ±10% from baseline with a tested substance at any given substance concentration.

RESULTS: Both L2 and G6 sensors showed interference with the following substances: dithiothreitol (maximal bias from baseline: L2/G6: +46%/-18%), galactose (>+100%/+17%), mannose (>+100%/+20%), and N-acetyl-cysteine (+11%/+18%). The following substances were found to interfere with L2 sensors only: ascorbic acid (+48%), ibuprofen (+14%), icodextrin (+10%), methyldopa (+16%), red wine (+12%), and xylose (>+100%). On the other hand, the following substances were found to interfere with G6 sensors only: acetaminophen (>+100%), ethyl alcohol (+12%), gentisic acid (+18%), hydroxyurea (>+100%), l-cysteine (-25%), l-Dopa (+11%), and uric acid (+33%). Additionally, G6 sensors could subsequently not be calibrated for use after exposure to dithiothreitol, gentisic acid, l-cysteine, and mesalazine (sensor fouling).

CONCLUSIONS: Our standardized dynamic interference testing protocol identified several nutritional, pharmaceutical and endogenous substances that substantially influenced L2 and G6 sensor signals. Clinical trials are now necessary to investigate whether our findings are of relevance during routine care.},
}

*Blood Glucose Self-Monitoring/instrumentation/methods
Humans
*Blood Glucose/analysis
*Biosensing Techniques/methods
Continuous Glucose Monitoring