@article {pmid41049074,
year = {2025},
author = {Sun, X and Shen, L and Zheng, R and Tao, M and Chen, S},
title = {MRPL35 Attenuates Neonatal Parenteral Nutrition-Associated Cholestasis by Modulating the ROS/JNK/NF-κB Pathway.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {13489-13502},
pmid = {41049074},
issn = {1178-7031},
abstract = {OBJECTIVE: This study aimed to elucidate the role of the MRPL35/ROS/JNK/NF-κB signaling pathway in the pathogenesis of neonatal parenteral nutrition-associated cholestasis (PNAC) to identify underlying mechanisms and potential therapeutic targets.

METHODS: The study employed both human and animal models. Neonates receiving parenteral nutrition for at least 2 weeks were divided into PNAC (n=10) and control groups (n=13). A PNAC model was established in male Sprague-Dawley rats (parenteral nutrition for 14 days, n=6/group), with interventions including adenovirus-mediated MRPL35 overexpression and N-acetylcysteine (NAC) treatment. Inflammatory markers, oxidative stress indicators, and signaling pathway activation were assessed using ELISA, immunohistochemistry, qRT-PCR, and Western blotting.

RESULTS: Clinically, neonates with PNAC exhibited elevated serum levels of AST, DBil, TBA, TNF-α, and IL-1β, along with reduced levels of anti-inflammatory cytokines (IL-4, IL-10), increased ROS, and higher apoptosis in peripheral blood mononuclear cells (PBMCs). MRPL35 expression was significantly downregulated and JNK and NF-κB pathways were activated. In the animal model, PNAC rats showed severe liver injury, elevated TNF-α, IL-1β and ROS in hepatocytes, and higher hepatocyte apoptosis; the expression of MRPL35 mRNA was significantly downregulated. Overexpression of MRPL35 reduced JNK/NF-κB activation, inflammatory cytokines, oxidative stress and liver injury, effects that were enhanced by co-treatment with N-acetylcysteine (NAC).

CONCLUSION: The MRPL35/ROS/JNK/NF-κB signaling pathway plays a critical role in the pathogenesis of PNAC. Targeting MRPL35 is expected to alleviate liver injury by blocking mitochondrial ROS signaling, offering a novel precision treatment model targeting the mitochondrial-inflammation axis for PNAC.},
}

@article {pmid41045636,
year = {2025},
author = {Sreevaram, HH and Kishore, A and Sivanesan, S and Prabhakaran, M and Karunakaran, B and Kasirajan, SP and Jyothi, AK and Maria Francis, Y},
title = {Comparative neuroprotective efficacy of N-acetylcysteine and naringin in lead-induced neurotoxicity: Restoration of BDNF, neurotransmitters, and cognitive function.},
journal = {Morphologie : bulletin de l'Association des anatomistes},
volume = {109},
number = {367},
pages = {101075},
doi = {10.1016/j.morpho.2025.101075},
pmid = {41045636},
issn = {1286-0115},
abstract = {BACKGROUND: Exposure to lead acetate is reported to induce neurotoxicity associated with cognitive dysfunction, neurotransmitter dysfunction, oxidative stress, neuroinflammation, and neuronal damage in the hippocampus. Flavonoids and other natural compounds possessing antioxidant and neuroprotective properties can be of therapeutic interest. In the current study, naringin's protective property as a flavonoid was compared with that of N-acetylcysteine (NAC) against lead-induced neurotoxicity in rats.

METHODS: Adult rats were randomly distributed into control, lead acetate-treated, lead+NAC-treated, lead+low-dose naringin, and lead+high-dose naringin groups, each group containing 6 animals. The Novel Object Recognition (NOR) test was used for the evaluation of cognitive function. Biochemical analysis of hippocampal glutamate, acetylcholine, Brain-Derived Neurotrophic Factor (BDNF), Nuclear factor erythroid 2-related factor 2 (Nrf2), pro-inflammatory markers (IL-6, GFAP), and serum lead levels was done. Histopathological analysis of hippocampal sections by crystal violet staining was done.

RESULTS: Exposure to lead acetate-induced severe neurotoxicity in the guise of compromised recognition memory, reduced glutamate and acetylcholine content, reduced BDNF and Nrf2 expression, increased IL-6 and GFAP content, and severe hippocampal neuronal damage. NAC treatment effectively reversed cognitive function, neurotransmitter content, neurotrophic factors, and diminished neuroinflammation. Dose-dependent neuroprotection was afforded by naringin, where the high-dose group had better recovery in all the parameters than the low-dose group. Interestingly, high-dose naringin was similar to or even larger than that of NAC's neuroprotection, normalization of hippocampal histoarchitecture, enhancement of antioxidant defense, and decrease in pro-inflammatory markers and serum lead levels.

CONCLUSION: Lead acetate causes profound neurotoxicity on cognition, neurotransmission, oxidative stress, and inflammation. Naringin, especially at high doses, exhibits highly potent neuroprotective effects, such as NAC, preventing lead-induced cognitive dysfunction and hippocampal pathology by displaying antioxidant, anti-inflammatory, and neurotrophic effects. The results propose naringin as a potential natural drug candidate for preventing and/or treating lead-induced neurotoxicity.},
}

@article {pmid41044637,
year = {2025},
author = {Havaldar, AA},
title = {Successful management of paraquat poisoning: a case report.},
journal = {Journal of medical case reports},
volume = {19},
number = {1},
pages = {479},
pmid = {41044637},
issn = {1752-1947},
mesh = {Humans ; *Paraquat/poisoning ; Adult ; Male ; Female ; *Herbicides/poisoning ; *Immunosuppressive Agents/therapeutic use/administration & dosage ; *Cyclophosphamide/therapeutic use/administration & dosage ; Acetylcysteine/therapeutic use ; Treatment Outcome ; Renal Replacement Therapy/methods ; India ; },
abstract = {BACKGROUND: Paraquat is a herbicide used for weed control and is one of the lethal poisons associated with high mortality. Exposure to this compound could be accidental or as a deliberate self-harm. Clinical manifestations can range from mild symptoms initially to multiorgan failure. Owing to high case fatality (50-90%) and no specific antidote is available; different treatment regimens are proposed with variable success rates. Here, we present two patients with paraquat poisoning, their initial presentation, clinical progress, and successful management.

CASE PRESENTATION: Two young adults, one 29-year-old male and one 32-year-old female patient from South India, presented with gastrointestinal symptoms and worsening renal and Liver failure. Patients had already received gastric lavage at the local hospital and later transferred to our hospital. We initiated immunosuppressive therapy with cyclophosphamide at 15 mg/kg/day for 3 days and steroids. Both patients received renal replacement therapy and N-acetyl cysteine infusion. We observed improvement in clinical and biochemical parameters over a week. There were no respiratory symptoms throughout the hospitalization. At the time of discharge, both patients were off renal replacement therapy. On long-term follow-up after 2.5 years, both patients had recovered well without any renal dysfunction.

CONCLUSION: This case report highlights the successful management of paraquat poisoning with high-dose cyclophosphamide with steroids. The timely initiation of immunosuppression prevented disease progression and facilitated prompt recovery.},
}

Humans
*Paraquat/poisoning
Adult
Male
Female
*Herbicides/poisoning
*Immunosuppressive Agents/therapeutic use/administration & dosage
*Cyclophosphamide/therapeutic use/administration & dosage
Acetylcysteine/therapeutic use
Treatment Outcome
Renal Replacement Therapy/methods
India

@article {pmid41038427,
year = {2025},
author = {Silva, SANM and Machado, FDS and Santos, LS and de Castro, MVL and Nogueira, ML and Soares, MBP and Alves Serafim Rocha, S and Araújo, RM and Dias, RB and Bezerra, DP and Araújo, AJ and Marinho Filho, JDB},
title = {CORDIAQUINONE B INDUCES CYTOTOXICITY AND OXIDATIVE STRESS-MEDIATED APOPTOSIS IN HUMAN COLORECTAL CANCER CELLS IN VITRO AND IN VIVO.},
journal = {Chemico-biological interactions},
volume = {},
number = {},
pages = {111764},
doi = {10.1016/j.cbi.2025.111764},
pmid = {41038427},
issn = {1872-7786},
abstract = {Cordiaquinones are natural molecules derived from the Varronia and Cordia genera with diverse biological potential. In this work, the effects of Cordiaquinone B were initially evaluated in a panel of cancer cell lines. Subsequently, it was first-hand investigated both in vitro and in vivo in human colorectal adenocarcinoma (HCT-116) cells. Experiments were conducted using two-dimensional (2D) and three-dimensional (3D) cell cultures and in the HCT-116 xenograft model in immunodeficient CB17-SCID mice. Cordiaquinone B inhibited the viability of both adherent and non-adherent cancer cell lines without inducing hemolysis in human erythrocytes. In Cordiaquinone B-treated HCT-116 cells, morphological changes and alterations in apoptosis-related protein levels were observed, indicating an apoptotic mechanism associated with mitochondrial oxidative stress. This was supported by an increased mitochondrial superoxide content and prevention of observed cytotoxic and apoptotic effects by N-acetylcysteine (NAC) pretreatment. In the 3D tumor model of HCT-116 spheroids, Cordiaquinone B treatment led to a spheroid size reduction. Additionally, in CB17-SCID mice, a dose of 3 mg/kg/day inhibited HCT-116 tumor growth by 42.6% without causing severe organ toxicity or alterations in hematological parameters, except for mild to moderate hepatic and pulmonary alterations. These results demonstrate the efficacy of Cordiaquinone B and highlight its potential as a promising candidate for colorectal cancer therapy.},
}

@article {pmid41032464,
year = {2025},
author = {Li, H and Wei, X and Sun, H},
title = {Molecular Insights into Bismuth's New Applications against Antimicrobial Resistance and Coronaviruses.},
journal = {Accounts of chemical research},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.accounts.5c00471},
pmid = {41032464},
issn = {1520-4898},
abstract = {ConspectusBismuth, a heavy metal distinguished by its low toxicity, compared to lead or mercury, has long been associated with medicine for the treatment of various conditions, notably as a key component in triple and quadruple therapies for eradicating Helicobacter pylori, including antibiotic-resistant strains. Compounds such as bismuth subsalicylate (BSS) and colloidal bismuth subcitrate (CBS) enhance the efficacy of antibiotics, e.g., metronidazole and tetracycline. Over the past two decades, the knowledge on the molecular mechanism of action of bismuth drugs has been significantly advanced, in particular with the aid of the metallomics/metalloproteomics, facilitating the discovery of novel therapeutic applications beyond H. pylori eradication.This Account describes how the molecular mechanism of action of bismuth drugs was unveiled at a system level by multiple-metalloproteomics approaches, which enable the comprehensive identification of bismuth-binding proteins with diverse affinities in bacteria. By integration with other techniques such as proteomics, bioinformatics and molecular biology, the sustained efficacy of bismuth drugs was attributable to their capacities to disrupt multiple biological pathways through binding and functional perturbation of key enzymes, in particular, those enzymes bearing CXnC (n = 2, 7), CXnH (n = 5, 6) and HXnH (n = 0-2, 8) motifs, in consistence with the thiophilic nature and high acidic property of bismuth.The generated knowledge on the mode of action of bismuth drugs lays a solid foundation for further exploration of their novel therapeutic applications. Our extensive studies have revealed that bismuth drugs and compounds hold great potential as versatile agents in combating antimicrobial resistance (AMR) crisis through co-therapies with clinically used antibiotics. This includes bismuth drugs as broad-spectrum inhibitors of metallo-β-lactamases (MBLs), enzymes responsible for resistance to β-lactam antibiotics, to fight against MBLs-positive bacterial infection together with β-lactams; bismuth drugs serve as adjuvants of Cefiderocol (Fetroja), the only clinically approved sideromycin, against infections caused by multidrug-resistant Pseudomonas aeruginosa and Burkholderia cepacia; bismuth drugs (and relevant compounds) in combination with clinically used antibiotics could combat Pseudomonas aeruginosa infections by disrupting iron homeostasis and functionally impairing Fe-S cluster-containing enzymes in multidrug-resistant Pseudomonas aeruginosa; newly developed bismuth compounds serve as novel metalloantibiotics to combat AMR. Moreover, the ability of bismuth to disrupt key zinc finger proteins for the transcription and replication in coronavirus rendered its new potential in treating coronavirus infections, particularly SARS-CoV-1 and SARS-CoV-2. Combining clinically used bismuth drugs with N-acetyl cysteine (NAC), a thiol-containing drug, increases bismuth uptake in blood plasma to therapeutic levels for SARS-CoV-2 without apparent toxicity. Bismuth drugs, therefore, hold great potential for the treatment of viral infections.We anticipate that our mechanism-guided discoveries of bismuth's new therapeutic applications are poised to inspire researchers in relevant fields to rationally design drugs (and metallodrugs) and repurpose FDA-approved drugs, ultimately leading to the development of new effective therapeutics for combating emerging infectious diseases, which will positively impact human health and well-being.},
}

@article {pmid41031098,
year = {2025},
author = {Leavy, OC and Goemans, AF and Hernandez-Beeftink, T and Stockwell, AD and Allen, RJ and Guillen-Guio, B and Adegunsoye, A and Booth, HL and Fahy, WA and Fingerlin, TE and Virk, HS and Hall, IP and Hart, SP and Hill, MR and Hirani, N and Kaminski, N and Ma, SF and McAnulty, RJ and Sheng, XR and Millar, AB and Molina-Molina, M and Navaratnam, V and Neighbors, M and Parfrey, H and Saini, G and Sayers, I and Strek, ME and Tobin, MD and Whyte, MKB and Zhang, Y and Maher, TM and Molyneaux, PL and Oldham, JM and Yaspan, BL and Flores, C and Martinez, F and Reynolds, CJ and Schwartz, DA and Noth, I and Jenkins, RG and Wain, LV},
title = {Sex-specific genetic effects on susceptibility to idiopathic pulmonary fibrosis.},
journal = {ERJ open research},
volume = {11},
number = {5},
pages = {},
pmid = {41031098},
issn = {2312-0541},
abstract = {BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that is more prevalent in males than females. The reasons for this are not fully understood; differing environmental exposures due to historically sex-biased occupations and diagnostic bias are possible explanations. To date, over 20 independent genetic association signals have been reported for IPF susceptibility, but these have been discovered when combining males and females. The objectives of the present study were to assess whether there is a need to consider sex-specific effects when evaluating genetic risk in clinical prediction models for IPF and to test for sex-specific associations with IPF susceptibility.

METHODS: We performed a genome-wide single nucleotide polymorphism (SNP)-by-sex interaction study meta-analysis of IPF risk in six independent case-control studies comprising 4561 cases (1280 females, 3281 males) and 22 888 controls (8360 females, 14 528 males) of European genetic ancestry. We used polygenic risk scores (PRSs) comprising common (minor allele frequency >1%) autosomal variants to assess differences in genetic risk prediction between males and females.

RESULTS: The predictive accuracy of the PRSs were similar between males and females, regardless of whether using combined or sex-specific association results. Three new independent genetic association signals were identified (p<1×10[-6]).

CONCLUSIONS: The predictive accuracy of common autosomal SNP-based PRSs did not vary significantly between males and females. We prioritised three genetic variants whose effect on IPF risk may be modified by sex. These findings would not account for the differences in prevalence between males and females. Future studies should ensure adequate representation of both sexes.},
}

@article {pmid41030491,
year = {2025},
author = {Iguh, C and Bakhsh, I and Grujic, S},
title = {Acute Hepatitis in a Patient Treated With Ribociclib for Metastatic Breast Carcinoma.},
journal = {Journal of medical cases},
volume = {16},
number = {9},
pages = {372-380},
pmid = {41030491},
issn = {1923-4163},
abstract = {Ribociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, is widely used in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Although hepatotoxicity is a recognized adverse effect, severe cases of ribociclib-induced liver injury with histologic confirmation of submassive hepatic necrosis remain rare. We describe a case of a postmenopausal woman with newly diagnosed stage IV HR+/HER2-negative invasive lobular carcinoma who developed acute hepatocellular injury 8 weeks after initiating ribociclib and anastrozole. The patient presented with fatigue, jaundice, and dark urine, and was found to have markedly elevated transaminases (alanine aminotransferase 1,825 U/L; aspartate aminotransferase 1,536 U/L) and hyperbilirubinemia. A thorough workup excluded viral, autoimmune, and obstructive hepatobiliary causes. Liver biopsy demonstrated confluent centrilobular necrosis without fibrosis or significant inflammation. Causality assessments yielded an R-factor of 20.73, a Roussel Uclaf Causality Assessment Method score of 10 (highly probable), and a Naranjo score of 7 (probable). Ribociclib was discontinued and intravenous N-acetylcysteine (NAC) initiated, leading to gradual normalization of liver enzymes. The patient was maintained on anastrozole alone, with no recurrence of liver injury and stable disease at 13-month follow-up. This case highlights the potential for ribociclib to induce severe hepatocellular injury with histologic evidence of submassive necrosis. Early recognition and structured causality assessment ensures patient safety. In patients with significant hepatotoxicity, discontinuation of ribociclib and non-rechallenge may be prudent. Furthermore, consideration of NAC in management is important in cases demonstrating persistent transaminitis despite ribociclib discontinuation.},
}

@article {pmid41023622,
year = {2025},
author = {Diako, K and Rahimi, S and Mirbagheri Saghaleksari, SA and Mousavi Eshkelani, SM and Keshavarz Taramsari, N and Beigi Harchegani, A and Mohsenifar, Z and Shahriarinour, M and Ranji, N},
title = {N-Acetylcysteine as an anti-oxidant and anti-inflammatory agent in decreasing histopathological damages and oxidative stress after mercury exposure in lung tissue of rats.},
journal = {BMC biotechnology},
volume = {25},
number = {1},
pages = {108},
pmid = {41023622},
issn = {1472-6750},
abstract = {BACKGROUND: Mercury (Hg) is a naturally occurring heavy metal with high toxicitythat affects various organs. This study aimed to evaluate the protective effects of N-acetylcysteine (NAC) on the lung tissue of Wistar rats exposed to mercury.

METHODS: Rats were divided into five groups: H1 (control), H2 (single dose of Hg), H3 (continuous dose of Hg), H4 (single dose of Hg+ single dose of NAC), and H5 (continuous dose of Hg+ continuous dose of NAC). The expression levels of SOD1, NOS, TIMP1, Fibronectin1, HIF1, MPO, MMP2 and TIMP2 were analyzed using qRT-PCR.

RESULTS: Mercury levels in the blood and lung tissues significantly increased in the H2 and H3 groups compared to the H4 and H5 groups, respectively. Hg exposure in H3 group significantly (P < 0.001) led to the upregulation of MPO (4.55-fold), HIF1(4.31-fold), MMP2 (4.20-fold), TIMP1(3.18-fold), TIMP2 (4.83-fold), NOS (3.52-fold), and FN1 (3.52-fold), along with the downregulation of SOD1 (0.51-fold) compare to control group (H1). In contrast, rats treated with NAC after Hg exposure in H5 group significantly (p < 0.01–0.001) showed downregulation of MPO (2.49-fold), HIF1(2.12-fold), MMP2 (1.94-fold), TIMP1(1.92-fold), TIMP2 (1.96-fold), NOS (2.00-fold), and FN1 (1.90-fold), and upregulation of SOD1 (0.76-fold) compare to H3 group. A significant reduction in mercury levels was also observed in the blood and lung tissue of rats treated with NAC compared to those exposed Hg alone.

CONCLUSION: NAC exerts a protective effect against mercury-induced cytotoxicity and genotoxicity in rat lungs by scavenging mercury and modulating the expression of oxidative stress-related genes.},
}

@article {pmid41020832,
year = {2025},
author = {Cherneva, DI and Kehayova, G and Dimitrova, S and Dragomanova, S},
title = {The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence.},
journal = {Current issues in molecular biology},
volume = {47},
number = {9},
pages = {},
pmid = {41020832},
issn = {1467-3045},
abstract = {N-acetylcysteine (NAC) has garnered increasing interest for its neurotherapeutic capabilities beyond its recognized functions as a mucolytic agent and an antidote for acetaminophen toxicity. This review consolidates findings from both preclinical and clinical studies to investigate NAC's diverse modulatory effects on the central nervous system (CNS). NAC primarily functions as an antioxidant by replenishing glutathione and mitigating oxidative stress; however, it produces glutathione-independent effects through the modulation of mitochondrial redox systems, ferroptosis, and the Nrf2-ARE signaling pathway. It plays a significant role in neuroinflammatory processes by inhibiting the production of cytokines, the expression of iNOS, and the activation of microglia. Furthermore, NAC affects various neurotransmitter systems-including glutamatergic, dopaminergic, GABAergic, serotonergic, cholinergic, and adrenergic pathways-by modulating synaptic transmission, receptor activity, and transporter functionality. It promotes neuroprotection through the enhancement of neurotrophic factors, the preservation of mitochondrial integrity, and the upregulation of survival signaling pathways. Recent evidence also emphasizes NAC's role in gene expression and the regulation of cortisol levels. The extensive range of NAC's neurobiological effects highlights its therapeutic potential in treating neurodegenerative and neuropsychiatric disorders. Nevertheless, the variability in clinical outcomes indicates a pressing need for more focused, mechanism-based research.},
}

@article {pmid41019354,
year = {2025},
author = {Aziz, ND and Azeez, DD and Mosa, AU and Al-Kareem, ZA and Majeed, SA and Ghafil, FA},
title = {Hepatoprotective potential of N-acetyl cysteine in rats with phenytoin induced liver injury.},
journal = {F1000Research},
volume = {14},
number = {},
pages = {593},
pmid = {41019354},
issn = {2046-1402},
mesh = {Animals ; *Phenytoin/adverse effects/toxicity ; *Acetylcysteine/pharmacology/therapeutic use ; Male ; *Chemical and Drug Induced Liver Injury/prevention & control/pathology/drug therapy/blood ; Rats, Wistar ; Rats ; *Liver/drug effects/pathology ; Anticonvulsants/toxicity ; Aspartate Aminotransferases/blood ; Alanine Transaminase/blood ; Bilirubin/blood ; *Protective Agents/pharmacology ; },
abstract = {BACKGROUND: Phenytoin is an anticonvulsant medication that is effective in treating various seizure disorders. It is mostly metabolized by the liver, which increases the risk of PHT-induced hepatotoxicity.

AIMS: This study aimed to assess the effectiveness of N-acetylcysteine (NAC) in protecting the liver from phenytoin-induced hepatotoxicity in rats.

MATERIALS AND METHODS: Four sets of five rats male Wistar albino rats (Rattus norvegicus) used for this study was based on their availability, well-established physiology, and long history of use in pharmacological and toxicological studies each were used for analysis. Each of the four groups received different treatments: the control group received normal saline, one group received 200 mg/kg/day of NAC, another group received 5 mg/kg/day of phenytoin, and the fourth group received 200 mg/kg/day of both phenytoin and NAC. The treatments were administered orally by gavage for 45 days. Biochemical indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (TSB)) were measured in serum after the animals were anaesthetized and the experiment ended. Histological analysis was performed on liver specimens.

RESULTS: Our investigation showed that phenytoin significantly elevated liver enzymes and total serum bilirubin compared to the control and NAC groups. The concurrent administration of NAC and phenytoin led to a notable reduction in these biomarkers, excluding ALP levels. Moreover, the group that received NAC alone did not exhibit a significant increase in the levels of these biomarkers compared with the control group. The histopathological results were in agreement with the biochemical tests.

CONCLUSION: This study concluded that Concomitant administration of NAC and phenytoin lowered the risk of phenytoin-induced hepatotoxicity. Moreover, this study confirmed that NAC is relatively safe when administered for a relatively prolonged period.},
}

Animals
*Phenytoin/adverse effects/toxicity
*Acetylcysteine/pharmacology/therapeutic use
Male
*Chemical and Drug Induced Liver Injury/prevention & control/pathology/drug therapy/blood
Rats, Wistar
Rats
*Liver/drug effects/pathology
Anticonvulsants/toxicity
Aspartate Aminotransferases/blood
Alanine Transaminase/blood
Bilirubin/blood
*Protective Agents/pharmacology

@article {pmid41018992,
year = {2025},
author = {Miller, TJ and Qiu, L and Nevin, A and Williams, R and Beachy, W},
title = {"Too Much of a Good Thing": Inadvertent Acetaminophen Overdose in a Low-Weight Elderly Patient.},
journal = {Clinical case reports},
volume = {13},
number = {10},
pages = {e71031},
pmid = {41018992},
issn = {2050-0904},
abstract = {Commonly used for its analgesic and anti-pyretic properties, acetaminophen ("Tylenol") is effective in managing generalized pain. Complications arise with supratherapeutic dosing of acetaminophen, especially in elderly and frail individuals with diminished glutathione production and reduced metabolic drug clearance potential. Limited cases outline this danger and offer alternative dosing considerations to avoid drug-induced liver injury from acetaminophen (DILI). We present a unique case of an 89-year-old woman without prior liver disease who developed acute liver failure (ALF) while taking recommended dosing of acetaminophen. Physical exam was revealing for generalized abdominal pain, lethargy, and vomiting without ascites, jaundice, or asterixis upon admission. She progressed to ALF with encephalopathy and worsening transaminitis along with evidence of synthetic liver failure. With an elevated acetaminophen level and no prior history of liver disease with Tylenol dosing of 30 mg/kg/dose, DILI due to acetaminophen toxicity was suspected. N-acetylcysteine (NAC) and albumin infusions were initiated with improvement in transaminitis and acute tubular necrosis (ATN). The patient was discharged after 12 days to a rehabilitation facility for strength recovery without long-term sequelae or transplant. While 4000 mg/day dosing regimen is generally safe, it can be dangerous for certain patients. Using the typical pediatric, weight-based regimen of 15 mg/kg as a framework, this patient represents a 66% higher dose than recommended. Considering her frailty and age, this case emphasizes the importance of patient-specific risk factors in acetaminophen dosing and prioritizing an individualized, weight-based approach to analgesic management.},
}

@article {pmid41016202,
year = {2025},
author = {Zhang, Y and Huang, C and Qiu, Y and Li, R and Liu, J and Du, Y and Li, D},
title = {Synergistic elimination of bacillus Calmette-Guérin biofilm and tissue restoration facilitated by ultrasound-mediated nanoparticles and antioxidants.},
journal = {International immunopharmacology},
volume = {166},
number = {},
pages = {115582},
doi = {10.1016/j.intimp.2025.115582},
pmid = {41016202},
issn = {1878-1705},
abstract = {Biofilm formation in Mycobacterium tuberculosis (MTB) enhances antibiotic resistance by impeding drug penetration and evading host immunity. This poses a significant challenge to conventional drug therapies, highlighting the urgent need for novel treatment strategies to overcome MTB's biofilm-mediated resistance. This study introduces the development of low-intensity ultrasound-mediated levofloxacin (LEV) and catalase (CAT) -loaded PEG-PLGA nanoparticles (LEV@CAT-NPs) for antimicrobial sonodynamic therapy (aSDT), offering an innovative strategy to combat BCG biofilm infection, by utilizing BCG as a model for MTB. N-acetylcysteine (NAC) was supplemented during the latter stages of the treatment process of anti-infection therapy to facilitate the transformation of macrophages to the M2 phenotype and to promote tissue repair. Ultrasound-mediated LEV@CAT-NPs, along with the subsequent addition of NAC not only enhanced repair at the infection site but also led to a progressive resolution of the inflammatory response in tissues. The treatment regimen induced a shift in macrophage polarization towards the M2 phenotype and modulated cytokine expression, decreasing pro-inflammatory while increasing anti-inflammatory cytokines, which contributed to the restoration of redox balance in the infected tissues. This study proposes a novel therapeutic strategy that not only targets drug-resistant MTB but also promotes tissue repair, highlighting its dual role in infection management.},
}

@article {pmid40944367,
year = {2025},
author = {Roussos, A and Kitopoulou, K and Borbolis, F and Ploumi, C and Gianniou, DD and Li, Z and He, H and Tsakiri, E and Borland, H and Kostakis, IK and Samiotaki, M and Trougakos, IP and Bohr, VA and Palikaras, K},
title = {Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-26},
doi = {10.1080/15548627.2025.2561073},
pmid = {40944367},
issn = {1554-8635},
abstract = {Mitochondrial dysfunction and impaired mitophagy are hallmarks of ageing and age-related pathologies. Disrupted inter-organellar communication among mitochondria, endoplasmic reticulum (ER), and lysosomes, further contributes to cellular dysfunction. While mitophagy has emerged as a promising target for neuroprotection and geroprotection, its potential to restore age-associated defects in organellar crosstalk remains unclear. Here, we show that mitophagy deficiency deregulates the morphology and homeostasis of mitochondria, ER and lysosomes, mirroring age-related alterations. In contrast, Urolithin A (UA), a gut-derived metabolite and potent mitophagy inducer, restores inter-organellar communication via calcium signaling, thereby, promoting mitophagy, healthspan and longevity. Our multi-omic analysis reveals that UA reorganizes ER, mitochondrial and lysosomal networks, linking inter-organellar dynamics to mitochondrial quality control. In Caenorhabditis elegans, UA induces calcium release from the ER, enhances lysosomal activity, and drives DRP-1/DNM1L/DRP1-mediated mitochondrial fission, culminating in efficient mitophagy. Calcium chelation abolishes UA-induced mitophagy, blocking its beneficial impact on muscle function and lifespan, underscoring the critical role of calcium signaling in UA's geroprotective effects. Furthermore, UA-induced calcium elevation activates mitochondrial biogenesis via UNC-43/CAMK2D and SKN-1/NFE2L2/Nrf2 pathways, which are both essential for healthspan and lifespan extension. Similarly, in mammalian cells, UA increases intracellular calcium, enhances mitophagy and mitochondrial metabolism, and mitigates stress-induced senescence in a calcium-dependent manner. Our findings uncover a conserved mechanism by which UA-induced mitophagy restores inter-organellar communication, supporting cellular homeostasis and organismal health.Abbreviations: Ca[2+]: calcium ions; BJ: human foreskin fibroblasts; BNIP3: BCL2 interacting protein 3; BP: bipyridyl; CAMK2D: calcium/calmodulin dependent protein kinase II delta; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DEGs: differentially expressed genes; DEPs : differentially expressed peptides; DFP: deferiprone; DNM1L/DRP1: dynamin 1 like; EGTA: ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid; EMC: endoplasmic reticulum membrane protein complex; ER: endoplasmic reticulum; FCCP: carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone; GO: gene ontology; GSVA: Gene Set Variation Analysis; HUVECs: human umbilical vein endothelial cells; IMM: inner mitochondrial membrane; ITPR/InsP3R: inositol 1,4,5-triphosphate receptor; MAM: mitochondria-associated ER membrane; MAPK: mitogen-activated protein kinase; MCU: mitochondrial calcium uniporter; MEFs: mouse embryonic fibroblasts; NAC : N-acetylcysteine; NFE2L2/Nrf2: NFE2 like bZIP transcription factor 2; NMN: nicotinamide mononucleotide; NR: nicotinamide riboside; OMM: outer mitochondrial membrane; PCA: principal-component analysis; PPARGC1A/PGC1α: PPARG coactivator 1 alpha; PQ: paraquat; TMCO: transmembrane and coiled-coil domains 1; TMRE: tetramethylrhodamine ethyl ester perchlorate; UA: urolithin A; VDAC: voltage dependent anion channel.},
}

@article {pmid41012520,
year = {2025},
author = {Josef, M and Abdellatif, MM and Abdelmonem, R and El-Nabarawi, MA and Teaima, M and Bedair, HM and Attia, A},
title = {Invasomes and Nanostructured Lipid Carriers for Targeted Delivery of Ceftazidime Combined with N-Acetylcysteine: A Novel Approach to Treat Pseudomonas aeruginosa-Induced Keratitis.},
journal = {Pharmaceutics},
volume = {17},
number = {9},
pages = {},
pmid = {41012520},
issn = {1999-4923},
abstract = {Objectives: This study was designed to optimize a ceftazidime (CTZ)-loaded nanocarrier that could efficiently permeate across corneal tissues. Moreover, N-acetylcysteine (NAC) was combined with an optimized CTZ-loaded formula to augment the antimicrobial activity and facilitate the efficient healing of Pseudomonas aeruginosa-induced keratitis. Methods: Different CTZ-loaded invasomes (INVs) and CTZ-loaded nanostructured lipid carriers (NLC) were fabricated and fully characterized via the determination of the entrapment efficiency (EE%), particle size (PS), surface charge, and percentage of CTZ release. Next, NAC was added to the optimized formulae from each nanocarrier, which were further assessed through ex vivo corneal permeation and in vitro antimicrobial activity studies. Finally, an in vivo evaluation of the optimal nanocarrier in the presence of NAC was performed. Results: Both nanocarriers showed nanoscale PS with sufficient surface charges. CTZ-loaded NLC formulae showed a higher EE% range with a sustained drug release profile. Both optimized formulae showed a spherical shape and excellent stability. Moreover, the antibacterial activity and biofilm inhibition assessments confirmed the synergistic effects of NAC when combined with different CTZ-loaded nanocarriers. However, the optimized CTZ-loaded INV formula achieved higher corneal permeation and deposition compared to the optimized CTZ-loaded NLC formula. Finally, the in vivo assessment confirmed the dominance of the optimized CTZ-loaded INV formula combined with NAC, where the microbiological, histopathological, and immunohistopathological examinations showed the rapid eradication of keratitis. Conclusions: Recent strategies for the incorporation of antibiotics into nanocarriers, combined with mucolytic agents, can offer a promising platform to boost the therapeutic efficiency of antibiotics and prevent antimicrobial resistance.},
}

@article {pmid41011426,
year = {2025},
author = {Shen, J and Li, Y and Miao, H},
title = {The PP2A Catalytic Subunit PPH21 Regulates Biofilm Formation and Drug Resistance of Candida albicans.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092093},
pmid = {41011426},
issn = {2076-2607},
abstract = {Candida albicans (C. albicans) biofilms exhibit enhanced resistance to conventional antifungal agents; however, the underlying pathogenic mechanisms warrant deeper exploration. Protein phosphatase 2A (PP2A), especially its catalytic activity, is crucial for maintaining physiological balance. This study focused on the role of the PP2A catalytic subunit coding gene PPH21 in biofilm formation and drug resistance of C. albicans. The mutant strain (pph21Δ/Δ) was generated and identified. The oxidative stress was detected by the reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The autophagic activity was evaluated, and the autophagosomes were observed by transmission electron microscopy (TEM). The biofilm formation was measured by XTT reduction assay, crystal violet (CV) staining, and scanning electron microscopy (SEM). The susceptibility to antifungal agents was examined by XTT reduction assay and spot assay. Additionally, the antioxidant N-acetylcysteine (NAC) was applied to clarify the regulatory effect of C. albicans autophagy on oxidative stress. The pathogenicity of PPH21 in oral C. albicans infection was evaluated through in vivo experiments. We found that PPH21 deletion led to increased oxidative stress and autophagic activities, but it can be reversed by the application of NAC. Moreover, PPH21 deletion also impaired the biofilm formation ability and reduced resistance to antifungal agents. Our findings revealed that PPH21 is involved in both virulence and stress adaptation of C. albicans.},
}

@article {pmid41011382,
year = {2025},
author = {Jotic, A and Cirkovic, I and Bozic, D and Savic Vujovic, K and Milovanovic, J and Folic, M and Trivic, A and Cvorovic, L and Radivojevic, N},
title = {Antibiofilm Effects of N-Acetyl Cysteine on Staphylococcal Biofilm in Patients with Chronic Rhinosinusitis.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092050},
pmid = {41011382},
issn = {2076-2607},
support = {451-03-65/2024-03/200110//Ministry of Science, Technological Development and Innovation, the Republic of Serbia/ ; },
abstract = {Staphylococcal bacterial biofilm plays an important role in the pathogenesis and bacterial persistence of chronic rhinosinusitis. N-acetyl cysteine (NAC) has an inhibitory role in biofilm formation, suppressing adhesion and matrix production or favoring dispersal of preformed biofilm. The aim of this study was to examine the in vitro effect of NAC on Staphylococcal biofilm formation by bacterial strains isolated from tissue samples of patients with chronic rhinosinusitis with or without nasal polyps (CRSwNP and CRSsNP). Prospective study included 75 patients with CRS. The biofilm-forming capacity of isolated strains was detected by microtiter-plate method and the effects of sub-inhibitory (1/2x, 1/4x, and 1/8x minimal inhibitory concentration, MIC) and supra-inhibitory minimal concentrations (2x, 4x, and 8xMIC) of NAC on biofilm production were investigated. Staphylococcal bacterial strains were isolated in 54 (72%) patients, and the most frequently isolated species were Staphylococcus aureus (40.7%). Coagulase-negative Staphylococci species were weak producers of biofilm, while S. aureus was a strong biofilm producer. Concentration of 3.1 mg/mL (1/2 MIC) was sufficient to completely prevent biofilm formation in 77.8% of the isolates, where 49.6 mg/mL (8xMIC) led to the complete eradication of formed biofilm in 81.5% of the isolates. The subinhibitory and eradication effects were dose- and strain-dependent. There were no significant differences in MIC values between isolates from patients with CRSwNP and CRSsNP isolates. NAC proved to be effective in inhibiting biofilm formation and reducing formed biofilm by Staphylococcal isolates from patients with CRS. A comparable antibiofilm effect was exhibited in both phenotypes of CRS, indicating that NAC's antibiofilm activity was independent of the underlying clinical phenotype, and more targeted on biofilm matrix components.},
}

@article {pmid41005550,
year = {2025},
author = {Sawyer, TW and Song, Y},
title = {Protective Effects of N-Acetylcysteine and its Amide Derivative Against Toxic Metals In Vitro: Potential Alternatives/Adjuncts to Traditional Chelators.},
journal = {Environmental toxicology and pharmacology},
volume = {},
number = {},
pages = {104825},
doi = {10.1016/j.etap.2025.104825},
pmid = {41005550},
issn = {1872-7077},
abstract = {The protective efficacies of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) against the toxicity of compounds containing arsenic, cadmium, cobalt, chromium and mercury, were compared to those of dimercaprol, dimercaptosuccinic acid, 2,3-dimercaptopropanesulphonate, D-penicillamine, and derivatives of ethylenediamine tetraacetic acid and diethylenetriaminepentaacetic in CHO-K1 cells. Both NAC and NACA were found to confer protection against these metals, with comparable or better efficacy than many of the test chelators. Results from studies using the glutathione synthesis inhibitor buthionine sulphoximine were consistent with NAC/NACA protection being mediated through both GSH up-regulation and chelation. Given NAC's activity against metal toxicity, widespread clinical use, parenteral or oral routes of administration, high clinical safety, low cost and ease of accessibility, it should be given consideration as a broad-spectrum protectant against toxic metal poisoning as a treatment or adjunct/combination treatment. Its more lipophilic derivative NACA, also warrants attention, especially in those cases where brain toxicity is a concern.},
}

@article {pmid41001250,
year = {2025},
author = {Rankin, TJ and Mayer, S and Laird, JG and Lobeck, B and Kalmanek, E and Drack, AV},
title = {N-Acetylcysteine Ameliorates Loss of the Electroretinogram b-wave in a Bardet-Biedl Syndrome Type 10 Mouse Model.},
journal = {Journal of experimental neurology},
volume = {6},
number = {1},
pages = {49-63},
pmid = {41001250},
issn = {2692-2819},
abstract = {Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder characterized by retinal degeneration leading to blindness. This study investigates the therapeutic efficacy of N-Acetylcysteine (NAC), an oxygen free radical scavenger, in ameliorating retinal degeneration associated with BBS using a murine model of BBS10. BBS is caused by mutations in BBS genes, the protein products of which are involved in ciliary function; mutant or absent BBS10 protein disrupts the assembly of the BBSome protein complex, disturbing ciliary trafficking and leading to photoreceptor cell dysfunction and death. Photoreceptor function can be assessed using the electroretinogram (ERG), and anatomy can be assessed using optical coherence tomography (OCT) and histology to demonstrate progressive degeneration over time. This study utilizes Bbs10 [-/-] mice to assess the effect of NAC supplementation on retinal degeneration. Results reveal that NAC supplementation ameliorates the progressive degeneration of the retinal outer nuclear layer (ONL) on OCT and mitigates the loss-of-b-wave ERG phenotype observed in Bbs10 [-/-] mice. The ERG b-wave is generated by retinal bipolar cells after synapsing with photoreceptors which have been hyperpolarized by light exposure. Reducing the loss-of-b-wave phenotype may indicate improved synaptic function. Synaptic staining demonstrates a correlation between the absence of an electropositive b-wave and mislocalized presynaptic terminals, highlighting the significance of synaptic integrity for retinal function. These findings suggest NAC as a promising therapeutic intervention for managing BBS10-related retinal degeneration.},
}

@article {pmid40998099,
year = {2025},
author = {Lawless, SC and Kelley, C and Nikulina, E and Tahir, U and Kaur, A and Alarcon, JM and Bergold, PJ},
title = {Chronic functional deficits following a single closed head injury in mice are prevented by minocycline and N-acetyl cysteine.},
journal = {Molecular and cellular neurosciences},
volume = {},
number = {},
pages = {104049},
doi = {10.1016/j.mcn.2025.104049},
pmid = {40998099},
issn = {1095-9327},
abstract = {Traumatic brain injury (TBI) can produce chronic limb coordination and gait deficits that are associated with ongoing white matter damage. In rodent TBI models, chronic motor deficits may be obscured by aging or motor compensation. In addition, there are no treatments for TBI. The murine closed head injury (CHI) model produces diffuse, chronic white matter injury that may underlie chronic white matter dysfunction and motor deficits. Evoked compound action potentials (CAP) assess corpus callosum function from 3 to 180-days post injury (DPI). CHI acutely decreases total CAP amplitudes that recover by 90 DPI and increase further at 180 DPI. Total CAP amplitude changes are blocked by dosing of minocycline and N-acetylcysteine beginning 12 h post-injury (MN12). Injured or sham mice have similar times to traverse or number of foot faults on beam walk. DeepLabCut™ markerless limb tracking provides limb positions used to develop novel assays to assess beam walk and simple/complex wheel. Absition analysis integrates the duration and extent of foot faults during beam walk. Injured mice develop absition deficits at 90 DPI that worsen at 180 DPI suggesting a chronic and progressive decline. Chronic absition deficits are blocked by MN12 treatment. Speed typically assesses performance on simple/complex wheel. Novel limb coordination assays show that at 180 DPI, injured mice decrease coordination that significantly correlates with increased total CAP amplitude. MN12 alleviates chronic corpus callosum dysfunction and motor deficits suggesting a strong efficacy to treat TBI. DeepLabCut™ limb tracking reveals chronic deficits and motor compensation not seen with standard outcomes.},
}

@article {pmid40995338,
year = {2025},
author = {Semnic, I and Rački, V and Perković, O and Vuletić, V},
title = {Mercury exposure leading to functional vitamin B12 deficiency and subacute combined degeneration: a case report and literature review.},
journal = {Frontiers in toxicology},
volume = {7},
number = {},
pages = {1580275},
pmid = {40995338},
issn = {2673-3080},
abstract = {INTRODUCTION: The association between neurological symptomatology and heavy metal exposure has been reported in the literature. A few cases of extrapyramidal symptomatology and subacute combined degeneration have been described as manifestations of mercury intoxication. We highlight a case of a patient presenting with Parkinsonian features (tremor, rigidity, and bradykinesia), pyramidal deficits, dysarthria, paresthesia, mild cognitive decline, and emotional lability, with proven elevated mercury levels in blood and hair and elevated arsenic in urine.

CASE: A 60-year-old man, with history of mercury exposure while working at the Centre for Waste Management and Environmental Protection presented to a neurologist after 10 months of persistent tremors, muscle spasms, paresthesia, and irritability, followed by the onset of bradykinesia, slurred speech, rigidity, insomnia, and subtle cognitive decline. Laboratory investigations revealed functional vitamin B12 and vitamin D deficiencies, while toxicological quantitative analysis showed elevated blood mercury levels (15.2 μg/L) and hair root levels (3 μg/g). MRI of the brain was normal, whereas MRI of the posterior cervical spine detected signs of myelopathy. Florodeoxyglucose (FDG) Positron Emission Tomography (PET) of the brain revealed bilateral temporal and parietal glucose hypometabolism, most pronounced in the left inferior parietal and left superior temporal regions. Single-Photon Emission Computed Tomography (SPECT) imaging of dopaminergic neurons in the striatum was negative, and the patient was unresponsive to levodopa. Multivitamin therapy (vitamins B, E, and D) with selenium, in combination with symptomatic therapy (benzodiazepines, muscle relaxants, and antidepressants) provided minimal relief, leading to the introduction of N-acetyl cysteine, which resulted in moderate improvement of symptoms. Physical and speech therapy were of great importance in this case.

DISCUSSION: This case is unique because it represents the development of therapy-resistant extrapyramidal symptoms over 3 years of mercury exposure, likely leading to subacute combined degeneration due to functional vitamin B12 deficiency. Epidemiological data describe methylmercury poisoning, known as Minamata disease, which presents with -somatosensory deficits, ataxia, parkinsonism, dysarthria, and visual and hearing impairments.

CONCLUSION: Toxicological screening for heavy metals in blood and urine should be considered in patients presenting with unexplained, levodopa-resistant extrapyramidal symptoms, behavioral and sleep disturbances, cognitive decline, and other non-specific neurological signs.},
}

@article {pmid40993955,
year = {2025},
author = {Marazziti, D and Caruso, V and Cappellato, G and Chiarantini, I and Gurrieri, R and Perrone, P and Violi, M and Crivelli, NSB and Weiss, F and Perugi, G},
title = {The Emerging Role of N-Acetylcysteine in Psychiatry: A Narrative Review of Available Data.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673365458250901115725},
pmid = {40993955},
issn = {1875-533X},
abstract = {N-acetylcysteine (NAC), a cysteine derivative with a reactive thiol group, possesses antioxidant and anti-inflammatory properties. Its redox activity plays a central role in scavenging reactive oxygen and nitrogen species and modulating cellular signaling pathways. Recent research highlights its potential role in psychiatric disorders through the modulation of oxidative stress and inflammatory pathways. This narrative review examines the efficacy of NAC in treating psychiatric conditions, including mood disorders, schizophrenia, anxiety disorders, post-traumatic stress disorder (PTSD), obsessive- compulsive disorder (OCD), substance use disorders (SUDs), and neurodevelopmental disorders. A comprehensive search of PubMed, Scopus, Embase, PsycINFO, and Google Scholar databases was conducted for studies published between March 1, 2007, and December 30, 2024. The search utilized keywords related to NAC and psychiatric disorders. Data were critically analyzed to evaluate NAC's therapeutic potential. Preclinical studies demonstrate NAC's benefits in reducing oxidative stress, inflammation, and modulating neurotransmitter systems. Animal models of depression, schizophrenia, and OCD show symptom reduction through glutamatergic and antioxidant mechanisms. Clinical trials reveal NAC's efficacy as an adjunct in treating major depressive disorder, bipolar disorder, and schizophrenia, particularly for negative and cognitive symptoms. Evidence for anxiety disorders, PTSD, and OCD is limited but suggests anxiolytic and anti-obsessive effects. In SUDs, NAC shows promise in reducing cravings and substance- seeking behavior, while preliminary findings in autism suggest improvements in irritability and hyperactivity. NAC exhibits potential as an adjunctive treatment for various psychiatric disorders due to its safety profile, low cost, and broad mechanisms of action. However, clinical results are mixed, highlighting the need for larger, well-designed trials to confirm its efficacy and define optimal dosing strategies.},
}

@article {pmid40990566,
year = {2025},
author = {Morrow, LM and Barr, EA and Grossi, E and Pillai, VK and Kight, KA and Wright, EB and Turner, RP and Swatzyna, RJ},
title = {Identifying Neuroinflammation: The Diagnostic Potential of Spindling Excessive Beta in the EEG.},
journal = {Clinical EEG and neuroscience},
volume = {},
number = {},
pages = {15500594251376475},
doi = {10.1177/15500594251376475},
pmid = {40990566},
issn = {2169-5202},
abstract = {This manuscript examines the pivotal role of neuroinflammation in the central nervous system (CNS), particularly considering the impact of the COVID-19 pandemic. Neuroinflammation serves as a defense mechanism against various insults, including toxins, infections, and trauma. However, if left untreated, neuroinflammation can become chronic, leading to significant symptomatic and structural brain damage. Notably, neuroinflammation can mimic psychological disorders, complicating diagnosis and treatment. Current diagnostic methods for neuroinflammation-such as lumbar punctures, MRIs, brain biopsies, blood tests, and PET scans-are often hindered by inaccuracy, invasiveness, and cost. This study posits that electroencephalography (EEG), particularly identifying spindling excessive beta (SEB) activity, offers a promising, non-invasive, and cost-effective alternative for detecting neuroinflammation. This study investigates the relationship between SEB activity and neuroinflammation, focusing on traumatic brain injury (TBI). Through statistical analysis of EEG data from 1,233 psychiatric patients, we identified and compared two groups: 75 non-benzodiazepine-using adults without TBI and 79 non-benzodiazepine using adults with TBI exhibiting SEB activity. We identified a significant prevalence of SEB in individuals with refractory psychiatric conditions, underscoring the significance of this biomarker for neuroinflammation. Furthermore, we examine the therapeutic implications of reducing SEB through interventions such as guanfacine combined with N-Acetyl Cysteine (NAC), photobiomodulation, and hyperbaric oxygen therapy, all of which have demonstrated efficacy in mitigating neuroinflammation. These findings suggest that EEG could play a transformative role in the early detection and management of neuroinflammatory conditions, paving the way for more personalized and effective treatments for mental health disorders.},
}

@article {pmid40988585,
year = {2025},
author = {Mohammad, A and Ibrahim, M and Akram, M and Mohsin, H and Imran, MT and Khan Alizai, HN},
title = {N-acetylcysteine for Parkinson's disease: a translational systematic review of mechanistic and early clinical data.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2025.2563489},
pmid = {40988585},
issn = {1758-2032},
abstract = {BACKGROUND: Parkinson's disease (PD) involves progressive motor and non-motor decline, linked to oxidative stress and glutathione depletion. N-acetylcysteine (NAC), a glutathione precursor and antioxidant, is a potential disease-modifying therapy.

OBJECTIVE: To evaluate preclinical and clinical evidence on NAC in PD, focusing on motor and non-motor outcomes, dopaminergic function, and oxidative stress biomarkers.

METHODS: A PRISMA-compliant review of MEDLINE and Embase (May 2025) identified prospective studies in animal models or adults with PD. Outcomes included Unified Parkinson's Disease Rating Scale (UPDRS), dopamine transporter (DAT) imaging, glutathione levels, and safety.

RESULTS: Twelve studies met criteria. Preclinical models showed consistent neuroprotection. Intravenous NAC raised brain glutathione levels; high-dose oral NAC reached CSF. Two open-label trials (n = 65), reported ~ 13% improvement in UPDRS scores and 4-9% dopamine transporter signal increases over three months. No serious adverse events were attributed to NAC.

CONCLUSIONS: Larger randomized controlled trials are needed to test efficacy and disease-modifying potential.},
}

@article {pmid40987193,
year = {2025},
author = {Tang, J and Chen, B and Yu, F and Xu, L and Yu, M and Wang, C and Zhang, F and Zhang, L and Yang, Y and Hou, J and Li, X and Xu, W and Zhang, N},
title = {BPA exposure activated estrogen receptor α (ER-α) and ROS to induce pyroptosis in cochlear hair cells.},
journal = {Ecotoxicology and environmental safety},
volume = {304},
number = {},
pages = {119094},
doi = {10.1016/j.ecoenv.2025.119094},
pmid = {40987193},
issn = {1090-2414},
abstract = {Increasing evidence links hearing loss to environmental pollutant exposure, with cochlear hair cell being a key target. Bisphenol A (BPA) has been suggested to cause ototoxicity, but its mechanism is not fully understood. In this study, cell viability was assessed by varying concentrations of BPA (0-150 μM) exposed to mouse cochlear hair cells (HEI-OC1), followed by RNA transcriptome sequencing to identify the possible molecular mechanisms. Results showed that BPA above 50 μM reduced cell viability in a dose-dependent manner. RNA sequencing identified 1764 differentially-expressed genes, comprised of 1152 up-regulated and 612 down-regulated genes. Notably, estrogen receptor-related genes were enriched, with a marked up-regulation of estrogen receptor α (ER-α) at both mRNA and protein levels. GO and KEGG analyses revealed the main pathway involvement for oxidative damage, lipid metabolism, protein phosphorylation, and DNA damage. STRING analyses constructed gene networks to identify functionally interacting genes correlated with pyroptotic pathways. BPA exposure induced pyroptosis-like morphological changes characterized by cell swelling, rounding, and membrane blebbing. Increased intracellular ROS and mitochondrial superoxide (MitoSOX) levels, reduced mitochondrial membrane potential (ΔΨm), and elevated intracellular calcium (Ca[2+]) levels were observed. Flow cytometry showed an increased proportion of apoptotic and necrotic cells. Pyroptosis-related genes, including caspase-3, caspase-8, caspase-9, and GSDME, were down-regulated, while IL-1β and IL-18 were up-regulated. Protein expressions of caspase-3, caspase-8, caspase-9, and GSDME were decreased, while cleaved caspase-3 and N-terminal GSDME (GSDME-NT) were increased. Furthermore, ROS inhibitor N-acetylcysteine (NAC) and the ER-α antagonist fulvestrant alleviated BPA-induced cell death, and suppressed the protein expressions of the pyroptotic pathway. These results demonstrate that BPA exposure induces ototoxicity possibly through activating ER-α and triggering mitochondrial ROS that contributes to pyroptosis.},
}

@article {pmid40977385,
year = {2025},
author = {Papke, V and Klimes-Dougan, B and Sahasrabudhe, SA and Mueller, BA and Park, YW and Öz, G and Eberly, LE and DiMaggio-Potter, ME and Kartha, RV and Cloyd, J and Coles, L and Cullen, KR},
title = {Examination of oxidative stress and glutamate as potential mechanisms of N-acetylcysteine in the treatment of non-suicidal self-injury in young people assigned female at birth: randomised trial.},
journal = {BJPsych open},
volume = {11},
number = {5},
pages = {e221},
doi = {10.1192/bjo.2025.10839},
pmid = {40977385},
issn = {2056-4724},
abstract = {BACKGROUND: Non-suicidal self-injury (NSSI) often emerges during adolescence and young adulthood. A prior open-label pilot study suggested that N-acetylcysteine (NAC) may reduce NSSI frequency in young individuals.

AIMS: This study investigated potential NSSI-related biological markers for NAC in young adults with a history of NSSI using a placebo-controlled, randomised clinical trial of two NAC dosage regimens.

METHOD: Forty-three individuals (assigned female at birth) aged 16-24 years and with a history of NSSI were randomly assigned to either low-dose NAC (3600 mg/day), high-dose NAC (5400 mg/day) or placebo treatment for 4 weeks. Participants underwent blood draws, magnetic resonance imaging with spectroscopy and clinical assessments before and after treatment. Primary outcomes included brain glutathione (GSH), blood reduced to oxidised GSH ratio and brain glutamate. Secondary outcomes included antioxidant protein levels, brain gamma-aminobutyric acid concentrations, functional connectivity (between amygdala and insula) and clinical outcomes. Pharmacokinetics, tolerability and correlations among measures were also explored.

RESULTS: For 39 participants who completed study assessments at follow-up, weekly NSSI and depression symptoms improved similarly across both treatment and placebo groups, with no significant group differences in primary or secondary outcomes at follow-up. Some significant correlations emerged.

CONCLUSIONS: The study did not support the proposed biological signatures of NAC in young adults with NSSI, although exploratory findings suggested potential biological correlates of clinical improvement. Further research is necessary to explore neurobiologically based treatments for young adults with NSSI.},
}

@article {pmid40619022,
year = {2025},
author = {Fang, L and Zuo, L and Xing, F and Wang, Y and Chen, R and Zhang, F and Zuo, D},
title = {Repositioning miconazole: a novel drug for inducing cell death and differentiation in myeloid leukemia.},
journal = {Biochemical pharmacology},
volume = {241},
number = {},
pages = {117126},
doi = {10.1016/j.bcp.2025.117126},
pmid = {40619022},
issn = {1873-2968},
mesh = {Humans ; Acetylcysteine/pharmacology ; Adenine/pharmacology/analogs & derivatives ; Amino Acid Chloromethyl Ketones/pharmacology ; *Antifungal Agents/pharmacology/therapeutic use ; *Apoptosis/drug effects ; Caspase Inhibitors/pharmacology ; Cell Differentiation/drug effects ; *Drug Repositioning ; HL-60 Cells ; K562 Cells ; *Leukemia, Myeloid, Acute/drug therapy ; *Miconazole/pharmacology/therapeutic use ; *Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors ; Male ; Animals ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays ; },
abstract = {Myeloid leukemia is a common form of blood cancer worldwide. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic member of the B-cell lymphoma-2 (BCL-2) family, is frequently overexpressed in various solid tumors and hematological cancers. Miconazole, a broad-spectrum anti-fungal agent, has exhibited anti-tumor properties against multiple cancer types, but its specific effects on leukemia remain unknown. The purpose of our research is to investigate whether miconazole targets MCL-1 to exert an anti-leukemic effect. Our research has demonstrated that miconazole directly binds to MCL-1 in HL60 and K562 cells, significantly inhibiting cell growth and decreasing MCL-1 protein levels, presumably by promoting MCL-1 degradation. Miconazole induces apoptosis, autophagy, and the production of reactive oxygen species (ROS). However, these effects can be attenuated by Z-VAD-FMK, 3-methyladenine (3-MA), and N-acetyl-L-cysteine (NAC). Meanwhile, miconazole-induced reduction of MCL-1 protein is reversed. Animal studies confirm the anti-myelocytic leukemia efficacy of miconazole in vivo. Unexpectedly, at low concentrations and with prolonged exposure, miconazole also promotes cell differentiation. This differentiation effect is positively associated with autophagy and ROS accumulation induced by miconazole, without altering MCL-1 expression. In conclusion, miconazole, identified through a drug repositioning (DR) approach, might be a potential therapeutic candidate for myeloid leukemia by either facilitating cell death or promoting cell differentiation.},
}

Humans
Acetylcysteine/pharmacology
Adenine/pharmacology/analogs & derivatives
Amino Acid Chloromethyl Ketones/pharmacology
*Antifungal Agents/pharmacology/therapeutic use
*Apoptosis/drug effects
Caspase Inhibitors/pharmacology
Cell Differentiation/drug effects
*Drug Repositioning
HL-60 Cells
K562 Cells
*Leukemia, Myeloid, Acute/drug therapy
*Miconazole/pharmacology/therapeutic use
*Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors
Male
Animals
Mice
Mice, Nude
Xenograft Model Antitumor Assays

@article {pmid40975184,
year = {2025},
author = {An, Z and Hu, H and Wang, Q and Qiu, Y and Chu, J and Xia, Y and Li, S},
title = {Dietary Selenium deficiency activates the NLRP3 inflammasome to induce gallbladder pyroptosis by regulating glycolysis and histone lactylation through ROS/HIF-1α pathway.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110118},
doi = {10.1016/j.jnutbio.2025.110118},
pmid = {40975184},
issn = {1873-4847},
abstract = {Selenium (Se) is an essential micronutrient, and inadequate intake can disrupt redox balance in digestive organs, promoting inflammation. Enhanced glycolysis leads to lactate accumulation, exacerbating the inflammatory response through inflammation-related pathways. Histone lysine lactylation plays a key role in epigenetic regulation. The effect of Se deficiency on the gallbladder remains unclear. To explore the mechanism of Se deficiency on gallbladder injury and the regulatory role of histone lactylation, we established Se-deficient swine models and in vitro cell models. Histopathological observation of the gallbladder found that Se deficiency led to inflammatory damage to the gallbladder. Metabolomics and proteomics results showed that Se deficiency led to significant enrichment of "glycolytic flux", "oxidative stress", and "hypoxia-inducible factor-1 α (HIF-1α) signaling pathway". Further studies have found that Se deficiency led to oxidative stress in gallbladder tissue, abnormal expression of HIF-1α factor, increased glycolysis levels, excessive lactate production, increased histone lactylation, and pyroptosis. HIF-1α knockdown suppressed Se deficiency-induced glycolysis and reduced lactate accumulation. In vitro studies using N-acetylcysteine (NAC), 2-deoxyglucose (2-DG), Oxamate and A-485 showed that Reactive oxygen species (ROS) regulated increased glycolysis through HIF-1α and increased H3K18 lactylation (H3K18la) levels through substrate-dependent modifications. Furthermore, H3K18la activated NLRP3 inflammasome, triggering pyroptosis and inflammatory cascades. In conclusion, the results of this study showed that dietary Se deficiency promotes glycolysis-dependent histone lactylation via the ROS/HIF-1α pathway, activating NLRP3 inflammasome, leading to pyroptosis and inflammation in gallbladder. These findings provide insights into targeted therapies for Se deficiency-related metabolic disorders and pathological changes in organs.},
}

@article {pmid40969002,
year = {2025},
author = {Wei, M and Xue, H and Gu, X and Zhang, K and Huang, Z and Lu, B and Ji, L},
title = {Chlorogenic acid promotes liver regeneration and repair after acetaminophen-induced liver injury via alleviating oxidative stress and enhancing fatty acid β-oxidation by activating Nrf2.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo01485a},
pmid = {40969002},
issn = {2042-650X},
abstract = {Acetaminophen (ACM)-induced hepatotoxicity involves an acute injury phase followed by a recovery phase. Although N-acetylcysteine (NAC) is widely used clinically to mitigate ACM-caused hepatotoxicity during the initial injury phase, effective therapeutic strategies to promote liver regeneration (LR) during the recovery phase remain unavailable. Chlorogenic acid (CGA), abundantly present in dietary sources, has been shown to exert significant hepatoprotective effects. This study reported that CGA not only promoted LR in mice following ACM (300 mg kg[-1]) intoxication (p < 0.05) but also significantly elevated the survival rate of mice treated with a lethal dose (500 mg kg[-1]) of ACM, increasing survival from approximately 9% to 45%. Mechanistically, CGA alleviated oxidative liver damage by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and facilitated energy supply for LR via enhancing fatty acid β-oxidation mediated by peroxisome proliferator-activated receptor α (PPARα). Genetic Nrf2 knockout (Nrf2[-/-]) and pharmacological inhibition of PPARα (using GW6471) confirmed the critical roles of both Nrf2 and PPARα in this process. Further analysis revealed that the CGA-induced Nrf2 activation upregulated the expression of peroxisome proliferator-activated receptor gamma, coactivator 1-alpha (PGC-1α), a key coactivator of PPARα. Collectively, CGA promoted LR following ACM intoxication by alleviating hepatic oxidative stress via activating Nrf2. Additionally, Nrf2 activation triggered the expression of PGC-1α, which further strengthened PPARα-mediated fatty acid β-oxidation, thereby supplying sufficient energy for CGA-promoted LR following ACM intoxication. These findings highlight CGA's hepatoprotective effects and suggest it as a promising dietary supplement for promoting LR following toxic injury.},
}

@article {pmid40961779,
year = {2025},
author = {Chen, S and Han, Q and Zhou, Z and Gao, M and Song, J and Zhang, B and Guo, Y and Lv, Z},
title = {Dietary N-acetylcysteine supplementation improves antioxidant capacity and production performance of breeder hens and offspring.},
journal = {Poultry science},
volume = {104},
number = {11},
pages = {105745},
doi = {10.1016/j.psj.2025.105745},
pmid = {40961779},
issn = {1525-3171},
abstract = {This study investigated the effects of dietary N-acetylcysteine (NAC) supplementation on the antioxidant capacity and production performance of broiler breeder hens and their offspring. The breeder hens were randomly assigned to two groups: one received a corn-soybean meal-based control diet, while the other was supplemented with 1 g/kg NAC. Eggs from each group were randomly selected for incubation, and the offspring broilers were fed a basal diet. Dietary NAC treatment not only increased the albumen height and Haugh unit values of eggs but also improved fertilization rates (P < 0.05). Additionally, broiler chicks from the NAC-treated hens demonstrated higher eviscerated weight, full evisceration rate, and semi-eviscerated weight (P < 0.05). Dietary supplementation with NAC in breeder hens enhanced antioxidant capacity, as evidenced by increased total antioxidant capacity and catalase (CAT) activity in egg yolk, elevated CAT and glutathione peroxidase activities in breeder hen serum, and higher superoxide dismutase activity in chick serum. In particular, the NAC-treated group showed significantly higher glutathione levels and lower malondialdehyde levels throughout the transition from breeder hens to offspring (P < 0.05). Furthermore, maternal NAC treatment decreased the relative mRNA expression levels of pro-inflammatory cytokines interferon-γ, interleukin 18, and interleukin 6 in the ileum of the offspring broilers (P < 0.05). In conclusion, maternal dietary supplementation with NAC can continuously enhance the antioxidant capability and intestinal barrier function of chicken offspring, while also improving egg quality, growth performance and slaughter performance.},
}

@article {pmid40954254,
year = {2025},
author = {El-Alamin, MMA and Elkhalek, OA and Azab, MM},
title = {An environmental green factorial design/assisted spectrofluorimetric technique for quantitation of citicoline in pharmaceutical dosage form and wastewater.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {32547},
pmid = {40954254},
issn = {2045-2322},
mesh = {*Wastewater/chemistry/analysis ; Spectrometry, Fluorescence/methods ; Limit of Detection ; Reproducibility of Results ; *Water Pollutants, Chemical/analysis ; o-Phthalaldehyde/chemistry ; Pharmaceutical Preparations/chemistry ; Green Chemistry Technology/methods ; },
abstract = {A novel, sensitive, and straightforward spectrofluorimetric method was developed for the quantitative determination of citicoline in pharmaceutical formulations and wastewater. The technique depends on the efficient derivatisation of the primary amino group of citicoline with O-phthalaldehyde (OPA) and N-acetylcysteine (NAC) in borate buffer (pH 11), yielding a highly fluorescent derivative. The fluorescence intensity was measured at 425 nm with an excitation wavelength of 341 nm. Experimental parameters affecting the derivatisation reaction were thoroughly optimised. Under optimal conditions, the method exhibited a linear response over the concentration range of 50.0-300.0 ng/mL, with an excellent correlation coefficient (R[2] = 0.9942). The limits of detection (LOD) and quantification (LOQ) were 6.4 ng/mL and 19.5 ng/mL, respectively. The approach demonstrated high accuracy and precision, with per cent recovery values close to 100% and a relative standard deviation (RSD) of 0.512%, confirming its reliability. Validation was done in agreement with ICH Q2(R1) guidelines, and statistical comparison with previously reported approaches indicated no significant difference in performance. The sustainability of the method was studied using the analytical greenness tools confirms the method's eco-friendly profile. Collectively, these contributions advance drug bioavailability while promoting a more efficient and sustainable analytical framework.},
}

*Wastewater/chemistry/analysis
Spectrometry, Fluorescence/methods
Limit of Detection
Reproducibility of Results
*Water Pollutants, Chemical/analysis
o-Phthalaldehyde/chemistry
Pharmaceutical Preparations/chemistry
Green Chemistry Technology/methods

@article {pmid40950264,
year = {2025},
author = {Long, S and Qin, H and Guo, J and Liu, L},
title = {Therapeutic outcomes and inflammatory modulation of inhaled N-acetylcysteine bronchoalveolar lavage in severe pneumonia.},
journal = {American journal of translational research},
volume = {17},
number = {8},
pages = {6630-6638},
pmid = {40950264},
issn = {1943-8141},
abstract = {OBJECTIVE: To evaluate the therapeutic efficacy of inhaled N-acetylcysteine (NAC) bronchoalveolar lavage (iNAC-BAL) in severe pneumonia (SP) and explore its effects on inflammatory cytokines modulation.

METHODS: A total of 146 SP cases were assigned to two groups: the control group received bronchoalveolar lavage with isotonic saline (0.9% NaCl) alone, while the observation group received additional NAC aerosol inhalation. Clinical efficacy, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, intensive care unit (ICU) stay, duration of ventilator dependence, adverse reactions, symptom resolution times, respiratory mechanics, pulmonary function, inflammatory cytokines, and humoral immunity were assessed and compared between the two groups.

RESULTS: The observation group achieved better therapeutic effects (P=0.007), with significantly lower APACHE II scores, shorter ICU stays, reduced ventilator dependence, faster symptom resolution, and fewer adverse events (all P<0.05). Additionally, respiratory dynamics, lung function, inflammatory cytokines, and humoral immunity improved markedly in the observation group compared with the control group (all P<0.05).

CONCLUSION: iNAC-BAL demonstrates significant clinical efficacy and potent anti-inflammatory effects in the management of SP.},
}

@article {pmid40948959,
year = {2025},
author = {Bohn, MC and Oltmanns, H and Harting, H and Meißner, J},
title = {N-acetyl cysteine as an additive to bone cement against pathogens involved in periprosthetic joint infections.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1595821},
pmid = {40948959},
issn = {2296-4185},
abstract = {Periprosthetic joint infections (PJIs) and septic loosening of implants are common complications following surgical replacement of destructive joints in both human and veterinary medicine. Increasing occurrence of multi-resistant bacteria and failure to manage periprosthetic joint infections make it necessary to identify new antibacterial substances for the treatment and prevention of these infections. N-acetyl cysteine (NAC), a derivative of the amino acid cysteine, has been chosen as a candidate substance due to its shown antibacterial activity. The aim of the study was to evaluate the suitability of NAC for the use together with polymethylmethacrylate bone cement in the context of PJIs. Antibacterial activity of pure NAC and NAC-containing bone cement against clinical isolates of Staphylococcus (S.) pseudintermedius was tested by determining minimal inhibitory concentrations, analyzing growth of bacteria on bone cement, and examining the influence on infection of human osteosarcoma (HOS) cells. Cytotoxicity of pure NAC and bone cement with NAC against HOS cells was analyzed with viability and proliferation assays, Live/Dead staining of cells on bone cement, measurement of Interleukin-6 (IL-6) release, and visualizing activation of p38 MAP kinase with Western blotting. NAC inhibited growth of Staphylococcus pseudintermedius at 2.5 mg/mL and reduced bacterial growth on bone cement but could not inhibit infection of cells at 1.5 mg/mL. The IC50 of pure NAC for viability was 3.6 mg/mL. Bone cement with NAC reduced viability and proliferation at some concentrations but did not provoke IL-6 release. Western blots indicated that p38 could be activated following treatment with NAC. Taken together, antibacterial effectiveness could be shown but cytocompatibility of NAC in bone cement was limited, so that NAC cannot currently be used as a bone cement additive. Further research is necessary to balance antibacterial activity and cytotoxicity.},
}

@article {pmid40947894,
year = {2025},
author = {Li, C and Zhang, Y and Pan, Y and Wu, H and Zhang, C and Wu, Y and Meng, R and Su, J},
title = {N-Acetylcysteine Promotes the Maturation of Sheep Oocytes and Embryo Development In Vitro.},
journal = {Reproduction in domestic animals = Zuchthygiene},
volume = {60},
number = {9},
pages = {e70084},
doi = {10.1111/rda.70084},
pmid = {40947894},
issn = {1439-0531},
abstract = {During the in vitro maturation process of oocytes, oxidative stress is commonly present, and excessive oxidative stress can affect oocyte maturation. Thus, adding antioxidants during maturation is an effective strategy for reducing oxidative stress. N-acetylcysteine (NAC), a derivative of cysteine, participates in glutathione (GSH) metabolism and stimulates glutathione synthesis. However, a clear understanding of the effect of NAC on sheep oocytes remains unknown. In this study, we investigated NAC's impact on the maturation of sheep oocytes, and the results revealed that the maturation rate, and subsequently the cleavage and blastocyst formation, were significantly enhanced by incubation with 1 mM NAC. The GSH and Ca[2+] levels increased, and the cortical granules were significantly elevated, whereas the reactive oxygen species levels were significantly reduced in the 1 mM NAC-treated group. Additionally, the number of inner cell masses was significantly increased. The findings of this study support the hypothesis that NAC increases oocyte maturation rate by protecting them from oxidative stress damage. These discoveries provide a new approach for improving the efficiency of in vitro production of sheep embryos.},
}

@article {pmid40945056,
year = {2025},
author = {Harvey, HJ and Szepe, KJ and Hendry, AC and Archer, DB and Avery, SV},
title = {Sorbic acid resistance and metabolism of Brettanomyces bruxellensis in the spoilage of low sugar soft drinks.},
journal = {International journal of food microbiology},
volume = {443},
number = {},
pages = {111439},
doi = {10.1016/j.ijfoodmicro.2025.111439},
pmid = {40945056},
issn = {1879-3460},
abstract = {Brettanomyces bruxellensis is an emerging spoilage yeast of low-sugar ethanol fermentation processes and alcoholic beverages. As soft (non-alcoholic) drinks manufacturers transition towards low sugar formulations, this study investigated the ability of B. bruxellensis to grow in different soft-drink and preservative conditions. Multiple B. bruxellensis isolates grew comparably to the common spoilage yeast Z. bailii in a variety of soft drink formulations, including zero sugar lemonades, low-sugar fruit juices, and carbonated beverages. Growth assays with B. bruxellensis in laboratory minimal-medium supplemented with low (0.1 %) glucose were characterised by turbid biomass accumulation (a spoilage indicator) and resistance to the major food preservative sorbic acid (SA), known to cause oxidative stress and to inhibit respiration. Analysis of respiro-fermentative metabolism revealed that B. bruxellensis favoured respiration over fermentation regardless of glucose concentration, with oxygen limitation significantly reducing its growth. Cell-to-cell heterogeneity was used as a tool to test whether cellular levels of respiratory reactive oxygen species (ROS) influence the organism's SA resistance phenotype. At low glucose, sorted cell-subpopulations with high background ROS were more SA resistant than low ROS cells. Furthermore, the antioxidant N-acetyl cysteine (NAC) hyper-sensitized these cell subpopulations to SA. Therefore, one explanation for SA resistance despite the organism's primarily respiratory metabolism could be that respiratory ROS builds cells' resilience to (subsequent) SA-induced oxidative stress. The work shows that B. bruxellensis is capable of growth in zero- or low-sugar media and drinks formulations, and in the presence of relatively high sorbic acid levels.},
}

@article {pmid40943427,
year = {2025},
author = {Albahri, G and Badran, A and Hellany, H and Baydoun, S and Abdallah, R and Alame, M and Hijazi, A and Maresca, M and Baydoun, E},
title = {Mandragora autumnalis: Phytochemical Composition, Antioxidant and Anti-Cancerous Bioactivities on Triple-Negative Breast Cancer Cells.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
doi = {10.3390/ijms26178506},
pmid = {40943427},
issn = {1422-0067},
abstract = {Breast cancer is a common and chronic condition, and despite improvements in diagnosis, treatment, and prevention, the number of cases of breast cancer is rising annually. New therapeutic drugs that target specific checkpoints should be created to fight breast cancer. Mandragora autumnalis possesses substantial cultural value as a herb and is regarded as one of the most significant medicinal plants; however, little is known about its anticancerous biological activity and chemopreventive molecular pathways against the triple-negative breast cancer (MDA-MB-231) cell line. In this study, the antioxidant, anticancer, and underlying molecular mechanisms of the Mandragora autumnalis ethanolic leaves extract (MAE) were evaluated, and its phytochemical composition was determined. Results indicated that MAE diminished the viability of MDA-MB-231 cells in a concentration- and time-dependent manner. Although MAE exhibited 55% radical scavenging activity at higher concentrations in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the attenuation of its cytotoxic effects in MDA-MB-231 cells with N-acetylcysteine (NAC) co-treatment suggests a potential role of oxidative stress. Additionally, MAE caused an increase in the tumor suppressor p53. Moreover, this extract caused a significant decrease in the expression of Ki-67 (a cellular proliferation marker), MMP-9 (matrix metalloproteinase-9, an enzyme involved in extracellular matrix degradation and metastasis), and STAT-3 (a transcription factor regulating cell growth and survival). Also, MAE altered cell cycle, cell migration, angiogenesis, invasion, aggregation, and adhesion to suppress cellular processes linked to metastasis. All of our research points to MAE's potential to function as an anticancer agent and opens up new possibilities for the development of innovative triple-negative breast cancer treatments.},
}

@article {pmid40939324,
year = {2025},
author = {Zhang, Y and Chen, J and Lin, W and Qin, Z and Zhou, D and Li, P and Xiong, W},
title = {Quantitative LC-MS/MS profiling of N-Acetylcysteine in chicken plasma: Method validation and pharmacokinetic characterization.},
journal = {Poultry science},
volume = {104},
number = {11},
pages = {105777},
doi = {10.1016/j.psj.2025.105777},
pmid = {40939324},
issn = {1525-3171},
abstract = {N-Acetylcysteine (NAC), an essential precursor in glutathione synthesis, exhibits broad therapeutic potential but remains pharmacokinetically (PK) poorly characterized in poultry. To address this gap, we developed and validated a novel LC-MS/MS method that incorporates an isotope-labeled internal standard (d[3]-NAC) and a surrogate matrix (5 mg/mL bovine serum albumin). This approach effectively overcame interference from endogenous thiols through one-step methanol protein precipitation followed by DTT reduction, with chromatographic separation on a C18 column using 0.1 % formic acid-acetonitrile gradient elution (0.3 mL/min). Method validation demonstrated excellent linearity (0.01-4 μg/mL, R[2] > 0.99), sensitivity (LOD: 0.005 μg/mL; LLOQ: 0.01 μg/mL), accuracy (84.9-114.77 %), and precision (RSD < 10.61 %). Pharmacokinetic studies in broilers revealed distinct profiles under intravenous (IV, 10 mg/kg) and oral administration (10, 20, 40 mg/kg): (1) IV injection achieved rapid high exposure (AUC0-t: 14.573 ± 2.2 h·μg/mL) with prolonged elimination (t1/2: 3.59 ± 2.59 h). (2) Oral dosing showed dose-proportional absorption (tmax: 0.65-0.81 h) but low bioavailability (F: 17.04-22.56 %), though higher doses accelerated absorption (t1/2 increased from 1.31 ± 0.19 h at 10 mg/kg to 3.40 ± 2.29 h at 40 mg/kg). These findings establish two clinical application paradigms: (1) IV administration is optimal for acute respiratory crises due to its immediate high plasma concentration. (2) Oral delivery suits chronic supplementation, with dose escalation enhancing absorption efficiency. The validated LC-MS/MS platform provides a robust solution for veterinary drug analysis in biologically complex matrices, while the PK insights directly inform rational NAC regimens in poultry respiratory disease management.},
}

@article {pmid40935016,
year = {2025},
author = {Zuo, H and Huang, L and Huang, M and Ma, X and Zheng, C and Holman, BWB and Zhang, Y and Luo, X and Mao, Y},
title = {Peroxiredoxin 6 (Prdx6) and oxidative stress in post-mortem beef tenderization: A proteomic perspective.},
journal = {Journal of proteomics},
volume = {},
number = {},
pages = {105527},
doi = {10.1016/j.jprot.2025.105527},
pmid = {40935016},
issn = {1876-7737},
abstract = {This research explored the role of peroxiredoxin 6 (Prdx6)-mediated non‑selenium glutathione peroxidase (NSGPx) activity in modulating the tenderization process of beef during post-mortem aging, extending up to 168 h. Shear force, NSGPx activity, differential protein abundance, heat shock proteins (HSP70, HSP27), and troponin-T levels were analyzed in beef longissimus lumborum muscles treated with hydrogen peroxide (H2O2), N-acetylcysteine (NAC), mercaptosuccinic acid (MA), or saline (Control). MA treatment inhibited NSGPx activity and accelerated tenderization compared to NAC. Proteomics revealed that proteins differentially abundant between 0 and 24 h post-mortem were linked to cytoskeleton, extracellular matrix, amino acid metabolism, and apoptosis pathways.MA upregulated HSP70 abundance, oxidative stress, and troponin-T breakdown. H2O2 upregulated HSP70 and HSP27 abundance only within 6-12 h post-mortem. These results demonstrate that oxidative stress treatments modulate protein dynamics during aging, offering insights into strategies to enhance beef tenderness. SIGNIFICANCE: This study highlights peroxiredoxin 6 (Prdx6) as a crucial regulatory element that affects oxidative stress-associated pathways involved in the meat tenderization process during post-mortem beef aging. We demonstrate that inhibiting Prdx6's on‑selenium glutathione peroxidase (NSGPx) enzymatic activity with mercaptosuccinic acid (MA) increases HSP70 abundance and accelerates troponin-T proteolysis through enhanced oxidative stress and calcium signaling pathways. Conversely, antioxidant N-acetylcysteine (NAC) delays tenderization by preserving cytoskeletal integrity. Our TMT-based proteomics further identifies 35 core proteins linking extracellular matrix remodeling, amino acid metabolism, and apoptosis to tenderness modulation. These findings provide the first mechanistic evidence that targeted manipulation of Prdx6 activity can optimize beef aging efficiency. For the meat industry, MA treatment offers a science-driven strategy to reduce tenderization time by >20 % within 24-72 h post-mortem, lowering processing costs while maintaining quality. This work also establishes HSP70 and troponin-T degradation as novel biomarkers for real-time monitoring of oxidative stress in meat processing systems.},
}

@article {pmid40931599,
year = {2025},
author = {Osman, AG and Avula, B and Khan, IA and Chittiboyina, AG},
title = {Unraveling Origins of N-Acetylcysteine (NAC): A Critical Review.},
journal = {Journal of dietary supplements},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/19390211.2025.2555015},
pmid = {40931599},
issn = {1939-022X},
abstract = {The controversial status of N-acetylcysteine (NAC) as a dietary supplement ingredient has renewed interest in its origin. This opinion article critically examines the scientific literature to investigate whether NAC is a naturally occurring compound, with a particular focus on its potential presence in plants. The primary objective of this opinion is to determine the natural occurrence of NAC, specifically within herbal matter. The classification of NAC as a dietary ingredient falls outside the scope of this analysis. We will rigorously evaluate the methodologies implemented in establishing NAC's presence in plant or herbal sources, specifically in Allium species which are often touted to contain NAC. By analyzing the strengths and weaknesses of prior research, we aim to clarify the evidence supporting the origin of NAC.},
}

@article {pmid40921646,
year = {2025},
author = {Morley, K and Arunogiri, S and Connor, JP and Clark, PJ and Chatterton, ML and Baillie, A and Slade, T and Berk, M and Lubman, D and Haber, PS},
title = {N-acetyl cysteine for the treatment of alcohol use disorder: study protocol for a multi-site, double-blind randomised controlled trial (NAC-AUD study).},
journal = {BMJ open},
volume = {15},
number = {9},
pages = {e091631},
doi = {10.1136/bmjopen-2024-091631},
pmid = {40921646},
issn = {2044-6055},
mesh = {Humans ; *Acetylcysteine/therapeutic use ; Double-Blind Method ; *Alcoholism/drug therapy ; Randomized Controlled Trials as Topic ; Cost-Benefit Analysis ; Adult ; Male ; Treatment Outcome ; Multicenter Studies as Topic ; Female ; Alcohol Drinking ; Cognition/drug effects ; },
abstract = {INTRODUCTION: Current treatments for alcohol use disorders (AUD) have limited efficacy. A previous 28-day pilot trial of N-acetyl cysteine (NAC) vs placebo found NAC to be feasible and safe, with evidence of improvement on some measures of alcohol consumption. Thus, the primary aim of the NAC-AUD study is to examine the therapeutic and cost-effectiveness of NAC vs placebo in improving treatment outcomes for AUD. We will also examine the (i) effect of NAC vs placebo on mood, markers of liver injury, cognition and hangover symptoms; and (ii) predictors of any response.

METHODS AND ANALYSIS: This double-blind trial will randomise participants with AUD to a 12-week regimen of either NAC (2400 mg/day) or placebo. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol (PEth). Secondary alcohol-related outcomes will include standard drinks per drinking day (SDDD) per week and absence of any HDDs. Other secondary outcomes will include markers of liver injury, depression, anxiety, craving, hangover symptoms, cognition and blood oxidative stress markers. We will also examine the cost-efficacy of NAC vs placebo.

ETHICS AND DISSEMINATION: Ethics approval for the study has been granted by The Sydney Local Health District Ethics Review Committee (X21-0342& HREC2021/ETH11614). There are no restrictions on publication from the sponsor or other parties.

TRIAL REGISTRATION NUMBER: NCT05408247.},
}

Humans
*Acetylcysteine/therapeutic use
Double-Blind Method
*Alcoholism/drug therapy
Randomized Controlled Trials as Topic
Cost-Benefit Analysis
Adult
Male
Treatment Outcome
Multicenter Studies as Topic
Female
Alcohol Drinking
Cognition/drug effects

@article {pmid40919813,
year = {2025},
author = {Ishii, K and Kurihara, Y and Yoshimura, M and Walenna, NF and Shimizu, A and Ozuru, R and Hiromatsu, K},
title = {FABP4-dependent fatty acid oxidation-fueled mitochondrial ROS induces the mobilization of cellular iron and facilitates Trypanosoma cruzi proliferation in murine adipocytes.},
journal = {mBio},
volume = {},
number = {},
pages = {e0218025},
doi = {10.1128/mbio.02180-25},
pmid = {40919813},
issn = {2150-7511},
abstract = {Fatty acid-binding protein 4 (FABP4) is a cytosolic lipid chaperone predominantly expressed in adipocytes. It has been shown that Trypanosoma cruzi targets adipose tissues and resides in adipocytes. However, how T. cruzi manipulates adipocytes to redirect nutrients for its benefit remains unknown. Here, we uncover the role of FABP4 in facilitating T. cruzi infection in murine 3T3-L1 adipocytes. We demonstrate that pharmacological or genetic inhibition of FABP4, carnitine palmitoyltransferase I (CPT-1), or fatty acid oxidation (FAO) abrogates the intracellular growth of T. cruzi in adipocytes. We also found that inhibiting FABP4, CPT-1, or FAO eliminates the infection-induced elevation of mitochondrial and cellular reactive oxygen species (ROS) in adipocytes. Furthermore, T. cruzi infection-induced elevation of ROS in adipocytes increased the cytosolic Fe[2+], which fueled T. cruzi proliferation. The treatment with antioxidants such as ROS scavenger N-acetyl cysteine (NAC) or mitochondrial ROS inhibitors MitoQ increased the expression level of mRNA for Ferroportin and Ferritin, leading to the decrease in cytosolic Fe[2+] and the intracellular growth inhibition of T. cruzi in adipocytes. The addition of ferrous sulfate reversed the FABP4 inhibitor or antioxidant-induced decrease in adipocyte parasite burden. Our results demonstrate that T. cruzi exploits host FABP4 to facilitate fatty acid oxidation and elevate cellular ROS, increasing the labile iron pool for the intracellular replication of T. cruzi in adipocytes. These results highlight the therapeutic possibility of host FABP4 as a drug target for T. cruzi infection.IMPORTANCEPersistent infection with a protozoan parasite, Trypanosoma cruzi, causes Chagas disease. While it has been appreciated that adipose tissues are one of the sites of persistent infection, the mechanism of how the parasite survives in adipocytes remains to be established. Our study highlights FABP4, a key regulator of metabolic dysfunction and inflammation, as a therapeutic host target controlling T. cruzi infection in adipocytes. We uncover the importance of FABP4 for T. cruzi replication in mouse adipocytes through engagement with lipid droplet degradation and trafficking of liberated free fatty acids to the host cell's mitochondria, which are utilized for fatty acid oxidation (FAO). T. cruzi infection-induced FAO fuels reactive oxygen species, and the subsequent iron mobilization accelerates parasite replication. These results shed light on the mechanisms of T. cruzi persistent infection in adipocytes, raising the possibility of host FABP4 as a drug target for T. cruzi infection.},
}

@article {pmid40917936,
year = {2025},
author = {Ma, Z and Xu, Q and Xu, X},
title = {The Pathophysiological Role of Mitochondrial Oxidative Stress in Rheumatic Diseases.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {12021-12044},
pmid = {40917936},
issn = {1178-7031},
abstract = {Mitochondria play a crucial role in reactive oxygen species (ROS)-dependent rheumatic diseases, including ankylosing spondylitis, osteoarthritis (OA), systemic lupus erythematosus (SLE) and scleroderma. Mitochondrial DNA (mtDNA), which encodes mitochondrial proteins, is more vulnerable to oxidants compared to nuclear DNA. When mtDNA gets damaged, it leads to mitochondrial dysfunction, such as electron transport chain impairment and loss of mitochondrial membrane potential. Moreover, the damaged mtDNA functions as a damage-associated molecular pattern (DAMP), triggering inflammatory and immune responses. In this review, ROS-related transcription factors and downstream cell signaling pathways are investigated. It also explains the mechanism of mitochondrial dysfunction and the clinical significance of major rheumatic diseases, as well as the clinical transformation status of key antioxidants, the risks/reasons for promoting mitochondrial ROS research in rheumatic diseases, and antioxidant therapy. We conclude that targeting oxidative stress with antioxidant agents,such as polyphenols, garlic, pomegranate, Coenzyme Q10, probiotic, α-lipoic acid, N-acetylcysteine (NAC), selenium, microalgae, fucoidan, resveratrol, quercetin, and curcumin should be considered as promising new strategies for treating rheumatic diseases lacking effective treatments.},
}

@article {pmid40700980,
year = {2026},
author = {Li, Y and Li, Y and Chen, H and Chen, Y and Ni, Y and Ji, J and Wang, K and Jin, Q},
title = {Self-assembled copper-amino acid nanoleaves for targeted treatment of deep-seated bacterial infections via chemodynamic therapy and cuproptosis-like death.},
journal = {Biomaterials},
volume = {325},
number = {},
pages = {123566},
doi = {10.1016/j.biomaterials.2025.123566},
pmid = {40700980},
issn = {1878-5905},
mesh = {*Copper/chemistry/therapeutic use/pharmacology ; Animals ; *Anti-Bacterial Agents/pharmacology/therapeutic use/chemistry ; Mice ; Biofilms/drug effects ; Reactive Oxygen Species/metabolism ; Humans ; Hyaluronic Acid/chemistry ; *Bacterial Infections/drug therapy ; *Amino Acids/chemistry ; Acetylcysteine/chemistry ; Female ; Mice, Inbred BALB C ; Microbial Sensitivity Tests ; },
abstract = {Transition metal ions such as Cu[2+] are promising broad-spectrum bactericidal agents. However, transition metal ions are not used to treat deep-seated bacterial infections in clinic owing to easy deactivation by proteins and lack of targeting ability. Herein, hyaluronic acid (HA)-modified copper-N-acetyl-l-cysteine (NAC) nanoleaves (CNH NLs) are developed to treat deep-seated bacterial infections by targeted delivery of Cu[2+] to infection sites. Cu-NAC nanoleaves (CN NLs) can be synthesized by coordinate assembly of Cu[2+] and NAC, which are further coated with HA to obtained CNH NLs with targeting ability. CNH NLs are stable in neutral physiological environment, while can be easily decomposed in acidic infection sites, leading to rapid release of Cu[2+]. The released Cu[2+] disrupts bacterial membranes, depletes glutathione, generates reactive oxygen species (ROS), and induces cuproptosis-like bacterial death, exhibiting potent activity against both planktonic bacteria and biofilms. The targeted accumulation and excellent therapeutic efficacy of CNH NLs is further confirmed on murine bacterial keratitis and pneumonia models, highlighting their therapeutic potential for deep-seated infections.},
}

*Copper/chemistry/therapeutic use/pharmacology
Animals
*Anti-Bacterial Agents/pharmacology/therapeutic use/chemistry
Mice
Biofilms/drug effects
Reactive Oxygen Species/metabolism
Humans
Hyaluronic Acid/chemistry
*Bacterial Infections/drug therapy
*Amino Acids/chemistry
Acetylcysteine/chemistry
Female
Mice, Inbred BALB C
Microbial Sensitivity Tests

@article {pmid40901687,
year = {2025},
author = {Koonsiripaiboon, P and Ruamtawee, W and Simasingha, N and Tanasoontrarat, W and Claimon, T and Sethasine, S},
title = {Efficacy of N-acetylcysteine vs dexamethasone in preventing postembolization syndrome post-transarterial chemoembolization in hepatocellular carcinoma: A randomized controlled trial.},
journal = {World journal of gastroenterology},
volume = {31},
number = {31},
pages = {109630},
doi = {10.3748/wjg.v31.i31.109630},
pmid = {40901687},
issn = {2219-2840},
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/pathology ; *Liver Neoplasms/therapy/pathology ; *Acetylcysteine/therapeutic use/administration & dosage ; Middle Aged ; Male ; *Chemoembolization, Therapeutic/adverse effects/methods ; Female ; Adult ; Double-Blind Method ; *Dexamethasone/therapeutic use/administration & dosage ; Aged ; Treatment Outcome ; Incidence ; Thailand/epidemiology ; Syndrome ; Young Adult ; Adolescent ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern in Thailand, with most patients diagnosed at the intermediate stage. Transarterial chemoembolization (TACE) is the standard treatment; however, postembolization syndrome (PES) remains a common complication. Although both dexamethasone (DEXA) and N-acetylcysteine (NAC) have shown efficacy in reducing PES, no study has directly compared their effects.

AIM: To compare the incidence of PES between DEXA and NAC in intermediate-stage HCC patients undergoing conventional TACE (cTACE).

METHODS: A randomized, double-blind, controlled trial was conducted at two tertiary hospitals in Thailand from November 2024 to April 2025. Eligible HCC patients (aged 18-70 years) were randomized (1:1) to receive either NAC (150 mg/kg/hour loading dose, followed by 50 mg/kg over 4 hours, then 6.25 mg/kg/ hour for 48 hours post-cTACE) or DEXA (8 mg IV 1 hour before cTACE). cTACE was performed by blinded interventional radiologists. The primary outcome was PES occurrence within 48 hours, assessed using South West Oncology Group toxicity coding and the Common Terminology Criteria for Adverse Events. The secondary outcomes were post-cTACE liver decompensation and the dynamic changes in the albumin-bilirubin (ALBI) score.

RESULTS: A total of 56 intermediate-stage HCC patients were included (DEXA, n = 28; NAC, n = 28). Most had preserved liver function, with 92.9% classified as Child-Pugh A. The maximum tumor size was 6.2 cm, and 85.7% had multiple lesions. Additionally, 39 patients (69.6%) met the beyond up-to-7 criteria. Overall, 27 patients (48.2%) developed PES. After adjusting for confounding factors, the NAC group had a significantly lower incidence of PES than the DEXA group (32.1% vs 64.3%; adjusted odds ratio = 0.17, 95% confidence interval: 0.03-0.87, P = 0.033). Only two patients (3.6%) developed post-cTACE liver decompensation. Furthermore, 51.8% patients experienced worsening ALBI scores within 48 hours post-procedure; however, the rate of ALBI score worsening did not significantly differ between the groups.

CONCLUSION: Compared with DEXA, NAC significantly reduces the incidence of PES, regardless of its impact on liver function recovery. Therefore, NAC is a preferable option for reducing PES in Barcelona Clinic Liver Cancer-B stage HCC patients with preserved liver function.},
}

Humans
*Carcinoma, Hepatocellular/therapy/pathology
*Liver Neoplasms/therapy/pathology
*Acetylcysteine/therapeutic use/administration & dosage
Middle Aged
Male
*Chemoembolization, Therapeutic/adverse effects/methods
Female
Adult
Double-Blind Method
*Dexamethasone/therapeutic use/administration & dosage
Aged
Treatment Outcome
Incidence
Thailand/epidemiology
Syndrome
Young Adult
Adolescent

@article {pmid40900813,
year = {2025},
author = {Kumar, S and Agrawal, P and Mendhey, P and Dhatwalia, SK and Sitasawad, SL},
title = {Antioxidants ameliorates glucose/glucose oxidase-induced myocardial damage through mitochondrial and MAPK pathway.},
journal = {3 Biotech},
volume = {15},
number = {9},
pages = {323},
doi = {10.1007/s13205-025-04441-z},
pmid = {40900813},
issn = {2190-572X},
abstract = {Diabetes is characterized by high blood glucose concentration that leads to the generation of elevated levels of free radicals (oxidative stress) via auto-oxidation. Oxidative stress plays a key role in diabetes-associated progressive pathologies including myocardial complications. The aim of the present study is to investigate the protective effects of antioxidants in glucose/glucose oxidase (G/GO)-dependent oxidative stress-induced cardiac cell damage. We found that exposure of G (33mM)/GO (1.6 milliunits) to cardiac muscle H9c2 cells resulted in a significant increase in apoptosis as indicated by accumulation of membrane phospholipid phosphatidylserine, DNA damage, and intracellular esterase activity. Confocal microscopy and FACS analysis further showed that G/GO induced the production of reactive oxygen and reactive nitrogen species which led to the loss of mitochondrial membrane potential and release of cytochrome c in H9c2 cells. Treatment of H9c2 cells with antioxidants like N-Acetyl Cysteine, catalase or glutathione abolished the G/GO-induced free radicals, perturbed the mitochondrial membrane potential, and induced cytochrome c release. These antioxidants also inhibited G/GO-induced cell death, caspases, and cleavage of PARP. In addition, antioxidants restored G/GO-induced suppression of antiapoptotic proteins, Bcl-2, Bcl-xL, cFLIP, XIAP, and survivin. Furthermore, G/GO impacted the MAPK pathway via activation of Raf1, MEK1 and ERK1/2 in oxidative stress-dependent manner. Pharmacologic inhibition of Raf1 also abolished G/GO-induced apoptosis. Thus, our data suggest that antioxidants have a strong protective efficacy against G/GO-induced oxidative stress through inhibition of mitochondrial and MAPK-mediated pathways in cardiac cells.},
}

@article {pmid40891511,
year = {2025},
author = {Narayanasamy, B and Helmueller, S and Zhang, Y and Lee, YJ},
title = {Current Advances in Anticancer Properties of Heptamethine Carbocyanine DZ-1 Conjugated to Artesunate: Generation of Reactive Oxygen Species.},
journal = {Journal of cellular biochemistry},
volume = {126},
number = {9},
pages = {e70062},
doi = {10.1002/jcb.70062},
pmid = {40891511},
issn = {1097-4644},
support = {//This study was supported by the following grants: National Institutes of Health R21CA259243 (Yong J. Lee), R01CA265827 (Yong J. Lee), R21CA256419 (Yi Zhang), and Department of Defense W81XWH-22-1-1095 RA210084 (Yong J. Lee)./ ; },
mesh = {Humans ; Artesunate ; *Reactive Oxygen Species/metabolism ; *Antineoplastic Agents/pharmacology/chemistry ; Apoptosis/drug effects ; *Artemisinins/pharmacology/chemistry ; Cell Line, Tumor ; *Carbocyanines/pharmacology/chemistry ; Membrane Potential, Mitochondrial/drug effects ; HCT116 Cells ; Cell Survival/drug effects ; Mitochondria/metabolism/drug effects ; },
abstract = {Heptamethine cyanine dyes and anticancer agents based conjugates are being developed for enhanced targeting and killing of cancer cells. DZ-1 dye conjugated agents induced cytotoxicity and mechanism of action have been shown in previous studies. In this study, a conjugated form of DZ-1 and artesunate (DZ-1-ART) was used to evaluate its cytotoxicity and elucidate the mechanism of actions in various cancer cell lines. Cells survival assays indicated dose-dependent cytotoxic activities of DZ-1-ART in HCT116, BxPC-3, and OVCAR-3 cell lines. Immunoblotting and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay confirmed involvement of apoptosis in DZ-1-ART-induced cytotoxicity. To elucidate the anticancer mechanism of the action of DZ-1-ART, MitoTracker and JC-1 assay were used. The results showed that translocation of DZ-1-ART in the mitochondria was followed by disruption of mitochondrial outer membrane potential. Dichlorofluorescin diacetate assay confirmed the generation of reactive oxygen species (ROS) in DZ-1-ART treated cancer cells. An antioxidant, N-acetyl cysteine treatment with DZ-1-ART showed reduction in cell death as well as suppression of ROS generation. When compared to HCT116 wild-type cells, Bak and Bax-deficient HCT116 cells also showed similar levels of cytotoxicity of DZ-1-ART. Taken together, this study's results reported that DZ-1-ART could induce mitochondria-mediated, ROS-generated, and Bak and Bax-independent apoptosis in cancer cells.},
}

Humans
Artesunate
*Reactive Oxygen Species/metabolism
*Antineoplastic Agents/pharmacology/chemistry
Apoptosis/drug effects
*Artemisinins/pharmacology/chemistry
Cell Line, Tumor
*Carbocyanines/pharmacology/chemistry
Membrane Potential, Mitochondrial/drug effects
HCT116 Cells
Cell Survival/drug effects
Mitochondria/metabolism/drug effects

@article {pmid40884714,
year = {2025},
author = {Sun, Y and Liu, C and Liang, Y and Lv, A and Nie, W and Bao, S and Li, X and Zhou, J and Tong, W and Tao, Y and Wang, X and Dong, T},
title = {Mitophagy Activation by N-Acetylcysteine Protects against Mic60 Deficiency-Induced Auditory Neuropathy.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {40884714},
issn = {1995-8218},
abstract = {Auditory neuropathy (AN) is a sensorineural hearing loss that impairs speech perception, but its mechanisms and treatments remain limited. Mic60, essential for the mitochondrial contact site and cristae organizing system, is linked to neurological disorders, yet its role in the auditory system remains unclear. We demonstrate that Mic60[+/-] mice develop progressive hearing loss from 6 months of age, with reduced auditory brainstem response amplitudes despite preserved outer hair cell function, consistent with AN. Mitochondrial abnormalities in spiral ganglion neurons (SGNs) emerge by 3 months, followed by mitochondrial loss and SGN degeneration, indicating progressive auditory neuron dysfunction. In vitro, Mic60 deficiency disrupts mitochondrial respiration, reversible by N-acetylcysteine (NAC). NAC treatment preserves mitochondrial integrity and rescues hearing by enhancing mitophagy. Our findings establish Mic60[+/-] mice as an AN animal model, highlight the role of Mic60 in the mitochondria of primary auditory neurons, and identify NAC as a potential AN treatment.},
}

@article {pmid40881937,
year = {2025},
author = {Moody, TW and Ramos-Alvarez, I and Mantey, SA and Jensen, RT},
title = {Bombesin Receptor Subtype-3 Regulates Tumor Growth by HER2 Tyrosine Phosphorylation in a Reactive Oxygen Species-Dependent Manner in Lung Cancer Cells.},
journal = {Targets (Basel)},
volume = {3},
number = {1},
pages = {},
doi = {10.3390/targets3010007},
pmid = {40881937},
issn = {2813-3137},
abstract = {Bombesin receptor subtype-3 (BRS-3) is a type 1 G-protein-coupled receptor. BRS-3 is an orphan GPCR which is structurally related to the neuromedin B and gastrin-releasing peptide receptors. When activated, BRS-3 causes phosphatidylinositol turnover in lung cancer cells. BRS-3 stimulates tyrosine phosphorylation of the epidermal growth-factor receptor (ErbB1), however it is unknown if it transactivates ErbB2/HER2. Adding the nonpeptide BRS-3 allosteric-agonist, MK-5046 or the peptide agonist, BA1 to the lung cancer cell line, NCI-H727 or BRS-3-transfected NCI-H1299 lung cancer cells, increased tyrosine phosphorylation of HER2/ERK2. This increase was antagonized by the BRS-3 peptide antagonist, Bantag-1 and the small molecule BRS-3 antagonist, ML-18. The increase in HER2/ERK phosphorylation caused by MK-5046 was inhibited by ROS inhibitors, N-acetylcysteine and Tiron (superoxide-scavenger). Adding MK-5046 to lung cancer cells increased reactive-oxygen species which was inhibited by NAC or Tiron. MK-5024 and BA1 increased NSCLC colony formation whereas, Bantag-1/ML-18 inhibited proliferation. These results indicate that in lung cancer cells activation of BRS-3 regulates HER2-transactivation in ROS-dependent manner which can mediate tumor growth. These results raise the possibility that the use of HER2-inhibiting compounds alone or in combination with other agents, could be a novel approach in the treatment of these tumors.},
}

@article {pmid40879897,
year = {2025},
author = {Stoddart, K and Davies, M and Oughton, J and Malcolm, E and AlSharari, SD and Shoaib, M},
title = {Selective Effects of Acutely Administered N-Acetyl-Cysteine in Rodent Models of Nicotine-Conditioned Behaviours.},
journal = {Addiction biology},
volume = {30},
number = {9},
pages = {e70051},
doi = {10.1111/adb.70051},
pmid = {40879897},
issn = {1369-1600},
support = {ORF-2025-829//King Saud University, Riyadh, Saudi Arabia: Ongoing Research Funding program/ ; //Faculty of Medical Sciences, Newcastle University/ ; },
mesh = {Animals ; *Acetylcysteine/pharmacology/administration & dosage ; *Nicotine/pharmacology/administration & dosage ; Rats ; Male ; Motor Activity/drug effects ; Dose-Response Relationship, Drug ; Disease Models, Animal ; *Tobacco Use Disorder/drug therapy ; *Nicotinic Agonists/pharmacology/administration & dosage ; Discrimination Learning/drug effects ; Conditioning, Operant/drug effects ; Rats, Sprague-Dawley ; Behavior, Animal/drug effects ; },
abstract = {Chronic nicotine administration leads to neuroadaptations, an important process in nicotine and tobacco dependence for which treatments are limited. The cysteine pro-drug, N-acetyl-cysteine (NAC), is a promising glutamatergic agent that has shown some clinical efficacy in reducing nicotine use in humans. The purpose of this study was to examine NAC in two rodent models of nicotine dependence. NAC (0, 5, 20, 50 and 100 mg/kg) was examined on locomotor activity in groups of rats previously exposed to nicotine or saline. In the second experiment, NAC (0, 50 and 100 mg/kg i.p.) was evaluated against the discriminative stimulus effects of nicotine (0.2 mg/kg) using a two-lever procedure under a tandem schedule (VI10"-FR10) of food reinforcement. Pre-treatment with NAC in doses greater than 20 mg/kg attenuated the expression of conditioned hyperactivity when rats were placed in locomotor boxes previously paired with chronic nicotine administration. The same doses of NAC had modest effects in attenuating nicotine-stimulated hyperactivity in nicotine-treated or saline-treated rats tested in the same locomotor boxes. In the discrimination task, NAC did not generalise to the nicotine stimulus and nor did it modify the dose-response curve to nicotine, suggesting that NAC may not modify the subjective effects of nicotine. These results suggest NAC selectively attenuates conditioned responses to nicotine-paired stimuli without modifying nicotine-induced hyperactivity or the discriminative stimulus effects of nicotine. Thus, the study proposes that if NAC was to act in a similar selective manner in humans, the specific action of NAC to attenuate conditioned responses may limit its potential as a treatment to manage nicotine dependence.},
}

Animals
*Acetylcysteine/pharmacology/administration & dosage
*Nicotine/pharmacology/administration & dosage
Rats
Male
Motor Activity/drug effects
Dose-Response Relationship, Drug
Disease Models, Animal
*Tobacco Use Disorder/drug therapy
*Nicotinic Agonists/pharmacology/administration & dosage
Discrimination Learning/drug effects
Conditioning, Operant/drug effects
Rats, Sprague-Dawley
Behavior, Animal/drug effects

@article {pmid40875537,
year = {2025},
author = {Back, SE and Gray, K and Jarnecke, AM and Saraiya, TC and Santa Ana, EJ and Killeen, T and Joseph, JE and Prisciandaro, JJ and Brown, DG and Nietert, PJ and Stecker, T and Rothbaum, A and Jones, JL and Flanagan, JC and Brady, KT},
title = {N-Acetylcysteine for the Treatment of Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder: A Double-Blind, Randomized Controlled Trial.},
journal = {The Journal of clinical psychiatry},
volume = {86},
number = {4},
pages = {},
doi = {10.4088/JCP.25m15803},
pmid = {40875537},
issn = {1555-2101},
mesh = {Humans ; *Acetylcysteine/therapeutic use/administration & dosage/adverse effects/pharmacology ; *Stress Disorders, Post-Traumatic/drug therapy/complications/therapy ; Adult ; Male ; Female ; Double-Blind Method ; Middle Aged ; *Alcoholism/drug therapy/complications/therapy ; Cognitive Behavioral Therapy/methods ; Aged ; Treatment Outcome ; Young Adult ; },
abstract = {Objective: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are common co-occurring conditions associated with a more severe clinical profile and poorer treatment outcomes than either disorder alone. To date, no medications have proven efficacious in the treatment of co-occurring PTSD/AUD. Methods: This randomized, double-blind, placebo-controlled trial examined the efficacy of N-acetylcysteine (NAC; 2,400 mg/day) among individuals (N=182, aged 21-65 years) who met DSM-5 criteria for current PTSD/AUD. Participants were randomized 1:1 to receive 12 weeks of NAC (n=93) or placebo (n=89). All participants received weekly, individual, cognitive behavioral therapy (CBT) for AUD. Follow-up visits occurred at 3-, 6-, and 12-months posttreatment. Primary outcomes included the Clinician Administered PTSD Scale for DSM-5 (CAPS-5), PTSD Checklist for DSM-5 (PCL-5), Timeline Follow-Back (TLFB), and the Obsessive Compulsive Drinking Scale at 12 weeks. The TLFB evaluated the frequency and amount of alcohol consumption. A secondary measure evaluated depression symptoms. Results: Intent-to-treat analyses showed that participants in both the NAC and placebo groups evidenced significant reductions in the CAPS-5 (B=-0.19, P<.001) and PCL-5 (B=-0.20, P<.001) during treatment, with no significant group differences. Both groups also showed significant reductions in alcohol use (drinks per drinking day [B=-0.02, P<.001], percent heavy drinking days [B=-0.14, P<.001], percent days abstinent [B=0.29, P=.022]) and craving (B=-0.12, P<.001) during treatment, but with no significant group differences. There were no group differences in retention or adverse events. Conclusions: Although NAC was well tolerated, it was not more effective than placebo in improving symptoms of PTSD or AUD when added to individual CBT for AUD. Trial Registration: ClinicalTrials.gov identifier: NCT02966873.},
}

Humans
*Acetylcysteine/therapeutic use/administration & dosage/adverse effects/pharmacology
*Stress Disorders, Post-Traumatic/drug therapy/complications/therapy
Adult
Male
Female
Double-Blind Method
Middle Aged
*Alcoholism/drug therapy/complications/therapy
Cognitive Behavioral Therapy/methods
Aged
Treatment Outcome
Young Adult

@article {pmid40873781,
year = {2025},
author = {Guan, H and Huang, L and Liu, Y and Zhu, E and Chen, L and Li, W and Wu, H and Zhang, X and Qin, R and Zheng, J and Mo, Y and Zhong, M and Xu, B and Dai, X and Wei, Q and Chen, Y and Wang, Q and Zheng, Z and Ma, K and Tang, C},
title = {Anti-PS IgG Immune Complexes Impair Macrophage Phagocytosis in SLE via LOX-Dependent Oxidative Stress.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {11521-11538},
pmid = {40873781},
issn = {1178-7031},
abstract = {PURPOSE: Systemic lupus erythematosus (SLE) is a severe autoimmune disease with systemic complications mediated by immune-complex formation. The elevated level of anti-phosphatidylserine (PS) IgG has been implicated in SLE pathogenesis. In this study, we aimed to explore the effector mechanisms of PS immune-complex during lupus development.

PATIENTS AND METHODS: Serological profiles of immune-complexes in SLE patients were analyzed. Immunofluorescence staining showed PS-IgG immune-complex deposition in kidney biopsies of lupus nephritis patients. C57BL/6J mice were immunized with PS for immune-complex and renal function assessment. The roles of PS-IgG immune-complex and lysyl oxidase (LOX) were validated from SLE PBMCs, THP-1 cell line and PS-immunized lupus mice. The intracellular reactive oxygen species (ROS) levels, and phagocytosis function were examined by flow cytometry in SLE PBMCs, THP-1 cell line and PS-immunized lupus mice. For in vitro treatment, the effects of antioxidant N-acetylcysteine (NAC) and LOX inhibitor β-Aminopropionitrile (BAPN) were verified in THP-1 cell line and cells from PS-immunized lupus mice.

RESULTS: SLE and lupus nephritis (LN) patients showed significant elevated circulating and glomerular PS-IgG immune-complex levels. ROC analysis indicated PS-IgG immune-complex as a strong biomarker in SLE and LN. Mechanistically, induced macrophages from SLE patients treated with PS-IgG immune-complex significantly increased cytoplasmic ROS levels, elevated LOX expression and exhibited dampened phagocytotic function. In mice, PS immunization triggered PS-IgG immune complex formation, increased LOX expression, immune-complex deposited glomerular nephritis, and impaired phagocytotic function of macrophages. NAC and BAPN treatment restored the phagocytotic function of human and murine macrophages.

CONCLUSION: Our results indicate that PS-IgG immune-complex can directly impair macrophage phagocytotic functions via LOX mediated-oxidative stress and may serve as a novel biomarker for SLE.},
}

@article {pmid40871026,
year = {2025},
author = {Altowijri, MA and Abdelmageed, ME and El-Gamal, R and Saeedi, T and El-Agamy, DS},
title = {Pristimerin Dampens Acetaminophen-Induced Hepatotoxicity; The Role of NF-κB/iNOS/COX-II/Cytokines, PI3K/AKT, and BAX/BCL-2/Caspase-3 Signaling Pathways.},
journal = {Pharmaceutics},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/pharmaceutics17081003},
pmid = {40871026},
issn = {1999-4923},
abstract = {Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways.},
}

@article {pmid40868982,
year = {2025},
author = {Jung, EJ and Kim, HJ and Shin, SC and Kim, GS and Jung, JM and Hong, SC and Kim, CW and Lee, WS},
title = {Tetraarsenic Hexoxide Enhanced the Anticancer Effects of Artemisia annua L. Polyphenols by Inducing Autophagic Cell Death and Apoptosis in Oxalplatin-Resistant HCT116 Colorectal Cancer Cells.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167661},
pmid = {40868982},
issn = {1422-0067},
support = {(2017R1D1A3B05030971)//Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education/ ; },
mesh = {Humans ; HCT116 Cells ; *Artemisia annua/chemistry ; *Apoptosis/drug effects ; *Polyphenols/pharmacology ; *Colorectal Neoplasms/metabolism/drug therapy/pathology ; *Drug Resistance, Neoplasm/drug effects ; *Autophagic Cell Death/drug effects ; Oxaliplatin/pharmacology ; *Antineoplastic Agents/pharmacology ; *Plant Extracts/pharmacology ; Cyclin D1/metabolism ; beta Catenin/metabolism ; Drug Synergism ; },
abstract = {It was reported that polyphenols extracted from Korean Artemisia annua L. (pKAL) have higher anticancer effects in oxaliplatin-resistant (OxPt-R) HCT116 cells than in HCT116 cells. In this study, it was tested whether and how As4O6 enhances anticancer effects of pKAL in HCT116 and HCT116-OxPt-R colorectal cancer cells. The CCK-8 assay, phase-contrast microscopy, and colony formation assay revealed that As4O6 enhanced anticancer effects of pKAL, with induction of nuclear deformity and intracytoplasmic vesicle formation in both cells. Western blot analysis revealed that co-treatment with As4O6 and pKAL significantly decreased the expression of NF-kB, EGFR, cyclin D1, CD44, and β-catenin, and upregulated the expression of p62 and LC3B in both cells. It also induced the activation of caspase-8 and γ-H2AX and the cleavage of β-catenin, PARP1, lamin A/C, and p62. These phenomena were inhibited by wortmannin, and further suppressed by co-treatment of wortmannin with an ROS inhibitor, N-acetyl cysteine. This study suggests that As4O6 enhanced the anticancer effects of pKAL by inducing autophagic cell death accompanied by apoptosis in both parental HCT116 and HCT116-OxPt-R cells. It also suggests that ROS generation and the downregulation of AKT, NF-κB p65, cyclin D1, EGFR, and β-catenin may play an important role in the As4O6-enhanced anticancer effect of pKAL.},
}

Humans
HCT116 Cells
*Artemisia annua/chemistry
*Apoptosis/drug effects
*Polyphenols/pharmacology
*Colorectal Neoplasms/metabolism/drug therapy/pathology
*Drug Resistance, Neoplasm/drug effects
*Autophagic Cell Death/drug effects
Oxaliplatin/pharmacology
*Antineoplastic Agents/pharmacology
*Plant Extracts/pharmacology
Cyclin D1/metabolism
beta Catenin/metabolism
Drug Synergism

@article {pmid40867878,
year = {2025},
author = {Kontoghiorghes, GJ},
title = {New Approaches and Strategies for the Repurposing of Iron Chelating/Antioxidant Drugs for Diseases of Free Radical Pathology in Medicine.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/antiox14080982},
pmid = {40867878},
issn = {2076-3921},
abstract = {There is an urgent need for new approaches and strategies for the introduction of antioxidant drugs in medicine. Despite hundreds of clinical trials with potential antioxidants, no antioxidant drugs have so far been developed for clinical use; this is mainly as a result of commercial reasons, but also due to insufficient data for regulatory authority approval. Antioxidant activity is a physiological process essential for healthy living. However, increased production of toxic free radicals and reactive oxygen species is observed in many clinical conditions, which are associated with serious and sometimes irreversible damage. Antioxidant drug strategies may involve short- to long-term therapeutic applications for the purpose of prevention, treatment, or post-treatment effects of a disease. These strategies are different for each disease and may include the design of protocols for the inhibition of oxidative damage through iron chelation, enhancing antioxidant defences by increasing the production of endogenous antioxidants, and activating antioxidant mechanisms, as well as the administration of synthetic and natural antioxidants. Both the improvement of antioxidant biomarkers and clinical improvement or disease remission are required to suggest effective therapeutic intervention. More concerted efforts, including new academic strategies, are required for the development of antioxidant drugs in clinical practice. Such efforts should be similar to the fulfilment of orphan or emergency drug regulatory requirements, which, in most cases, involve the treatment or clinical improvement of rare or severe diseases such as neurodegenerative diseases and cancer. Promising results of antioxidant therapeutic interventions include mainly the repurposing of the iron chelating/antioxidants drugs deferiprone (L1) and deferoxamine, and also the iron-binding drug N-acetylcysteine (NAC). In some clinical trials, the lack of pharmacodynamic and ferrikinetic data, wrong posology, and insufficient monitoring have resulted in inconclusive findings. Future strategies involving appropriate protocols and drug combinations, such as L1 and NAC, appear to improve the prospect of developing antioxidant drug therapies in different diseases, including those associated with ferroptosis. New strategies may also involve the use of pro-drugs such as aspirin, which is partly biotransformed into iron chelating/antioxidant metabolites with chemopreventive properties in cancer, and also in other therapeutic interventions. A consortium of expert academics on regulatory drug affairs and clinical trials could increase the prospects for antioxidant drug development in medicine.},
}

@article {pmid40865250,
year = {2025},
author = {Li, L and Tan, J and Chen, D and Luo, J and Li, P},
title = {Ethacrynic acid regulates gentamicin ototoxicity via the blood-labyrinth barrier.},
journal = {Hearing research},
volume = {466},
number = {},
pages = {109405},
doi = {10.1016/j.heares.2025.109405},
pmid = {40865250},
issn = {1878-5891},
abstract = {Gentamicin (GM), a widely used aminoglycoside antibiotic, has its clinical utility significantly limited by ototoxicity, which may be further exacerbated by co-administered drugs. This study systematically investigated the ototoxic mechanisms of GM combined with ethacrynic acid (EA) and the protective effects of N-acetylcysteine (NAC) using C57BL/6 J mice. Results revealed dose-dependent GM-induced ototoxicity. Intravenous administration caused more severe damage than intraperitoneal injection. Co-administration of EA synergistically potentiated GM toxicity. This exacerbated cochlear hair cell loss, auditory nerve fiber degeneration, and spiral ganglion neuron damage. Additionally, it induced systemic hepatorenal toxicity, manifested by increased macrophage activation and suppressed cell proliferation. EA disrupted inner ear homeostasis via a dual mechanism: impairing blood-labyrinth barrier integrity and triggering compensatory pericyte-mediated repair. NAC intervention significantly attenuated the combined toxicity. The pretreatment group showed the highest hair cell survival rate. Notably, EA facilitated NAC entry into the cochlea, enhancing its protective efficacy. Delayed EA administration (6 h post-GM) reduced hair cell damage by 50%. Furthermore, NAC ameliorated damage to neural fibers and synapses. This study shows that EA modulates GM ototoxicity by disrupting BLB equilibrium. The time-dependent nature of NAC intervention offers a strategy to prevent drug-induced hearing loss. These findings provide critical insights for optimizing clinical regimens involving aminoglycosides and loop diuretics.},
}

@article {pmid40863039,
year = {2025},
author = {Horvat Aleksijević, L and Lončar Brzak, B and Sikora, M and Škrinjar, I and Brailo, V and Andabak Rogulj, A and Aleksijević, M and Vidović Juras, D},
title = {Efficacy of N-Acetyl Cysteine in the Treatment of Burning Mouth Syndrome-A Randomized Controlled Trial.},
journal = {Dentistry journal},
volume = {13},
number = {8},
pages = {},
pmid = {40863039},
issn = {2304-6767},
support = {not applicable//University of Zagreb/ ; },
abstract = {Objectives: Burning mouth syndrome (BMS) is a chronic, painful, idiopathic condition of the oral cavity, characterized by the absence of visible pathological changes on the oral mucosa and normal laboratory findings. Recent evidence from the literature supports the classification of BMS as a neuropathic condition. It has been proposed that oxidative stress may contribute to neuropathic pain. N-acetylcysteine (NAC) is an antioxidant that exhibits neuroprotective properties. The aim of the study was to evaluate the efficacy of N-acetyl cysteine in the treatment of burning mouth syndrome (BMS). Methods: Eighty female patients with previously diagnosed BMS were randomly assigned to one out of two groups. One group received N-acetyl cysteine (600 mg/twice a day) and the other received placebo, for an eight-week period. The outcome was measured by the Oral Health Impact Profile-14 (OHIP-14) quality of life questionnaire and Numeric Pain Rating Scale, for burning and discomfort, both before and after completing the therapy. Results: Both groups experienced a significant reduction in burning and discomfort sensations, along with a significant improvement in oral health-related quality of life. However, the difference between the treatment and control group was not statistically significant. Conclusions: NAC does not significantly improve the oral health-related quality of life, burning sensations, and discomfort in BMS subjects compared to placebo.},
}

@article {pmid40859915,
year = {2025},
author = {Ma, C and Han, L and Yao, H and Zhao, W and Chen, F and Wu, X and Li, G and Huang, R and Pang, CH and Zhu, Z and Xu, J and Pan, G},
title = {Modulating G6PD/PGD to overcome FSP1/DHODH-mediated ferroptosis defence: A novel oridonin derivative suppresses liver cancer.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70160},
pmid = {40859915},
issn = {1476-5381},
support = {81872927//National Natural Science Foundation of China/ ; 82173679//National Natural Science Foundation of China/ ; XDA16020205//Chinese Academy of Sciences/ ; XDB1150102//Chinese Academy of Sciences/ ; CPU2018GY04//China Pharmaceutical University/ ; 2105DTPSIMM//University of Nottingham Ningbo China/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC), a globally prevalent malignancy with high mortality rates, presents an unmet need for innovative effective therapies.

PURPOSE: This study aimed to explore the antitumour potential of compound XD, a novel oridonin derivative, on HCC and its underlying mechanism.

EXPERIMENTAL APPROACH: The antitumour effects of compound XD were investigated in several HCC cells lines and mice models. The mechanism of XD was investigated using FACS, qPCR, WB, ELISA, IHC, siRNA and plasmid transfection.

KEY RESULTS: Compound XD demonstrated potent inhibitory effects, surpassing sorafenib with a maximum of 10-fold lower IC50 values against HCC cell lines. Its anticancer activities were ferroptosis dependent, which could be attenuated by ferroptosis inhibitors including deferoxamine, ferrostatin-1 and N-acetyl-cysteine. Unlike sorafenib, XD decreased two pivotal regulator FSP1 and DHODH to induce ferroptosis, while their overexpression partially mitigated XD-induced cytotoxicity and lipid peroxidation. In addition, XD treatment decreased cellular NADPH levels and inhibited the expression of G6PD and PGD in NADPH generation. Overexpression of G6PD or PGD reversed FSP1 and DHODH down-regulation, rescuing the ferroptosis induced by XD. Bioinformation analysis indicated the significant up-regulation of G6PD and PGD in clinical HCC patients and was positively correlated with cancer stages. Molecular docking and CETSA assay confirmed the binding capacity of XD with G6PD and PGD protein. Finally, XD dose-dependently inhibited liver tumour growth and induced ferroptosis-related markers in mice.

CONCLUSION AND IMPLICATIONS: This study suggests XD as a potential ferroptosis inducer and the potential role of G6PD/PGD/FSP1/DHODH axis in governing ferroptosis sensitivity in HCC.},
}

@article {pmid40858780,
year = {2025},
author = {Chetcuti, L and Hardan, AY and Frazier, TW and Loth, E and McPartland, JC and Youngstrom, EA and Uljarevic, M},
title = {Advancing scientific understanding of the drive to socially engage: from broad constructs to transdiagnostic 'building blocks'.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {40858780},
issn = {1476-5578},
support = {1R01MH129833//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; 1R01MH129833//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; 1R01MH129833//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; 1R01MH129833//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; },
abstract = {Reduced drive to socially engage is observed across neurodevelopmental and neuropsychiatric conditions. However, previous research has relied on disorder-specific conceptualizations and measurement approaches that might obscure important differences in how social drive manifests and its underlying neurobiological mechanisms, both within and across different diagnostic categories. In this commentary, we argue that a model of reward processing that deconstructs social drive into 'orienting', 'wanting', 'pursuing', 'liking' and 'learning' processes can advance mechanistic and phenomenological understanding. Implementing this framework necessitates a multimethod measurement approach, combining rigorously validated behavioral measures and neurobiological sampling while leveraging specific developmental principles within a longitudinal research framework. Through these concerted efforts, the field will make significant strides towards developing a biologically grounded account of clinical phenomena characterized by different profiles of atypical drive to engage with others, which is a first and critical step toward the development of accurate prediction models and specific treatments.},
}

@article {pmid40853509,
year = {2025},
author = {Malik, V and Kar, A and Venkatachalam, AM and Mandal, K},
title = {An Elegant Method of One-Pot Ligation-Desulfurization for High-Yielding Chemical Protein Synthesis.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e10194},
doi = {10.1002/advs.202510194},
pmid = {40853509},
issn = {2198-3844},
support = {RTI-4007//Department of Atomic Energy, Government of India/ ; },
abstract = {While native chemical ligation (NCL), combined with radical-mediated desulfurization, has enabled chemical syntheses of a vast array of proteins, the presence of aryl thiols as catalysts in the ligation mixture prevents performing both ligation and desulfurization reactions in one-pot, as aryl thiols are effective radical scavengers. Existing one-pot ligation and desulfurization approaches are not ideal as they rely on the use of inefficient alkyl thiols as NCL catalysts. Here an extremely efficient and impressively straightforward method is presented that utilizes bromoacetamide, in conjunction with N-acetyl cysteine, for selective quenching of arylthiol following NCL, enabling ligation and desulfurization in one-pot without any intermediate purification step. The reagent combination facilitates one-pot reactions by selectively capping aryl thiols in the presence of peptidic cysteine residue, leveraging the increased nucleophilicity of aryl thiols over alkyl thiols. N-acetyl cysteine additionally functions as the alkyl thiol additive for the desulfurization reaction. It is demonstrated the utility of this methodology by synthesizing three different proteins: ubiquitin, collagen, and barstar A. The strategy substantially enhances the efficiency of chemical protein synthesis, especially for cysteine-free proteins. Its operational simplicity and broad applicability make this one-pot ligation-desulfurization protocol promising for widespread adoption in synthesizing therapeutic proteins and related biomolecules.},
}

@article {pmid40851422,
year = {2025},
author = {Özer Aslan, İ and Öz, M and Erdal, H and Karaboğa, İ and Doğan, M},
title = {Protective effect of N-acetylcysteine in doxorubicin-induced primary ovarian failure in female rats.},
journal = {Turkish journal of obstetrics and gynecology},
volume = {},
number = {},
pages = {},
doi = {10.4274/tjod.galenos.2025.71654},
pmid = {40851422},
issn = {2149-9322},
abstract = {OBJECTIVE: N-acetylcysteine (NAC), an aminothiol compound, eliminates free radicals and enhances glutathione (GSH) synthesis, thereby strengthening intracellular antioxidant defenses. Although its protective effects against ovarian injury have been reported, its efficacy in doxorubicin (DOX)-induced ovarian failure has not been demonstrated. This study aimed to investigate whether NAC exerts a protective role against DOX-induced ovarian toxicity in female rats.

MATERIALS AND METHODS: Twenty-one adult female rats were randomly assigned to three groups: Control, DOX (10 mg/kg, i.p., single dose), and DOX+NAC (150 mg/kg, i.p., for 5 days; DOX administered on day 3, one hour after NAC). Serum and tissue oxidative stress parameters, histopathological changes, proliferating cell nuclear antigen (PCNA) immunoreactivity, and TUNEL assay were evaluated.

RESULTS: DOX significantly reduced serum anti-Müllerian hormone (AMH) (6.75 → 5.31 ng/mL; p<0.001) and GSH (422.64 → 280.98 mg/L; p<0.001), while increasing tumor necrosis factor alpha (TNF-α) (175.87 → 260.77 ng/L; p<0.001) and total oxidant status (TOS) (7.18 → 11.84 U/mL; p=0.002). NAC treatment reversed these alterations, namely: AMH (6.51 ng/mL; p=0.004), GSH (363.86 mg/L; p=0.018), TNF-α (184.55 ng/L; p<0.001), TOS (7.88 U/mL; p=0.003). In ovarian tissue, DOX reduced GSH (123.63 → 80.64 mg/L; p=0.001) and total antioxidant status (14.88 → 10.57 U/mL; p<0.001), while elevating TOS (7.14 → 12.64 U/mL; p<0.001) and caspase-3 (2.06 → 3.14 ng/mL; p<0.001). NAC significantly improved all these parameters (p≤0.005). Histologically, DOX caused edema, hemorrhage, infiltration, and a reduction in the percentage of healthy follicles, whereas NAC markedly ameliorated these alterations. Furthermore, NAC enhanced PCNA expression and reduced TUNEL-positive granulosa cells, supporting its anti-apoptotic effect.

CONCLUSION: NAC preserved ovarian reserve and follicular integrity by suppressing oxidative stress, inflammation, and apoptosis induced by DOX. These findings highlight NAC as a promising protective agent against chemotherapy-induced ovarian toxicity.},
}

@article {pmid40729908,
year = {2025},
author = {Zhao, Y and Niu, Y and Wang, X and Wan, P and Ma, Z and Sun, J and Jiang, S and Xue, L and Liu, N},
title = {N-Acetyl-L-Cysteine modulates indium-tin oxide nanoparticles-caused interstitial lung diseases in male rats through oxidative stress-activated apoptosis and autophagy.},
journal = {Ecotoxicology and environmental safety},
volume = {302},
number = {},
pages = {118716},
doi = {10.1016/j.ecoenv.2025.118716},
pmid = {40729908},
issn = {1090-2414},
mesh = {Animals ; Male ; Oxidative Stress/drug effects ; Apoptosis/drug effects ; Rats, Sprague-Dawley ; Autophagy/drug effects ; *Acetylcysteine/pharmacology ; *Tin Compounds/toxicity ; Rats ; *Lung Diseases, Interstitial/chemically induced/drug therapy ; *Metal Nanoparticles/toxicity ; Lung/drug effects ; },
abstract = {Indium-tin oxide nanoparticles (Nano-ITO) are widely used in various applications as infrared shielding materials, which increase the risk of occupational exposure. According to reports, Nano-ITO can cause indium lung disease in occupational exposed workers, but the specific mechanism of Nano-ITO-induced pulmonary toxicity remains unclear. In this study, 50 8-week-old male Sprague-Dawley rats were divided into five groups (10 rats in each group) as follows: control group (physiological saline), 1.2 mg/kg Nano-ITO group, 6 mg/kg Nano-ITO group, N-Acetyl-L-Cysteine (NAC) control group (200 mg/kg), and NAC + Nano-ITO group (200 mg/kg NAC intraperitoneal injection, after 1.5 h, 6 mg/kg Nano-ITO intratracheal instillation), twice a week for 12 weeks. Pathological and ultrastructural changes in the rat lung tissue, immunofluorescence assays, immunohistochemistry, protein and mRNA levels of apoptosis- and autophagy-related genes were measured. The levels of ROS, MDA, H2O2, and LDH, and the activities of T-AOC and SOD, were determined using oxidative stress assay kits. The results showed that Nano-ITO caused strong pulmonary inflammation, pulmonary alveolar proteinosis, and pulmonary interstitial fibrosis. In addition, Nano-ITO-induced oxidative stress in rat lungs presented as increased levels of ROS and H2O2 in the lungs, increased LDH and MDA levels, SOD and T-AOC activity in BALF, and activation of the Nrf2/NQO1/HO-1 signaling pathway. Intriguingly, Nano-ITO significantly increased the protein expression of microtubule-associated protein light chain 3 (LC3-II), the protein levels of autophagy-related genes 5 (ATG5), and Beclin-1 (BECN1), and reduced the protein levels of phosphatidylinositol 3-kinase (PI3K) in lung tissues. In addition, transmission electron microscopy (TEM) showed a significant increase in autophagic vesicles in the cytoplasm of lungs treated with Nano-ITO, indicating that Nano-ITO induces autophagy in rat lungs. Moreover, apoptosis also participates in Nano-ITO-induced pulmonary injury in a synchronous manner, as evidenced by the enhancement of TUNEL-positive signals and activation of the apoptosis pathway (Bax and Bcl-2 positive proportions). NAC supplementation restored most of the pathological structural features of rat lung tissue to their physiological range and effectively weakened apoptosis, as demonstrated by the notable reductions in TUNEL, Bax, and Bcl-2 protein expression levels in the lungs. Although autophagy was detected in the lungs of rats in the Nano-ITO and NAC + Nano-ITO groups, we discovered that NAC could rescue the expression of ATG5 and BECN1 induced by Nano-ITO, thus indicating that exposure to Nano-ITO promotes pulmonary apoptosis and autophagy by mediating oxidative stress. These results indicate that Nano-ITO can cause pulmonary injury by inducing oxidative stress, which activates apoptosis and autophagy, ultimately leading to alveolar proteinosis and interstitial fibrosis.},
}

Animals
Male
Oxidative Stress/drug effects
Apoptosis/drug effects
Rats, Sprague-Dawley
Autophagy/drug effects
*Acetylcysteine/pharmacology
*Tin Compounds/toxicity
Rats
*Lung Diseases, Interstitial/chemically induced/drug therapy
*Metal Nanoparticles/toxicity
Lung/drug effects

@article {pmid40847608,
year = {2025},
author = {Varela, ELP and Gomes, ARQ and da Silva Barbosa Dos Santos, A and Dos Santos Guimarães, M and de Carvalho, EP and Ferreira, OO and de Oliveira, MS and Iriti, M and de Aguiar Andrade, EH and Percário, S},
title = {Lycopene Mitigates Malaria-Induced Reactive Oxygen and Nitrogen Species and Oxidative Damage in Mice Brain and Lungs.},
journal = {Parasite immunology},
volume = {47},
number = {8},
pages = {e70019},
doi = {10.1111/pim.70019},
pmid = {40847608},
issn = {1365-3024},
support = {//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Brazil)/ ; //Fundação Amazônia Paraense de Amparo à Pesquisa (FAPESPA; Brazil)/ ; },
mesh = {Animals ; *Lung/pathology/drug effects ; Mice ; Lycopene ; *Brain/pathology/drug effects/metabolism ; Plasmodium berghei ; *Malaria/drug therapy/pathology ; *Antioxidants/administration & dosage ; *Oxidative Stress/drug effects ; *Reactive Oxygen Species/metabolism ; *Carotenoids/administration & dosage ; *Reactive Nitrogen Species/metabolism ; Thiobarbituric Acid Reactive Substances/analysis ; Male ; Nitric Oxide/analysis ; Female ; Disease Models, Animal ; },
abstract = {The severity of malaria is associated with low antioxidant availability and elevated free radical production, which induces oxidative damage in cerebral and pulmonary microcirculation. This can be mitigated by dietary antioxidants. We investigated the protective effects of lycopene (LYC) against oxidative changes induced by Plasmodium berghei (Pb). Mice were infected by intraperitoneal injection of 10[6] parasitized red blood cells and treated orally with LYC (3.11 mg/kg bw/day) or N-acetylcysteine (NAC, 62 mg/kg bw/day). Evaluations were conducted at 1-, 4-, 8- and 12-days post-infection. We measured thiobarbituric acid reactive substances (TBARS), antioxidant capacity by ABTS (AC-ABTS) and DPPH (AC-DPPH) inhibition, uric acid (UA) and nitric oxide (NO) in brain and lung tissues. Infection led to elevated TBARS, AC-ABTS, AC-DPPH, UA and NO, resulting in animal mortality. LYC significantly attenuated the infection-induced increases in TBARS, UA and NO levels compared to Pb (p < 0.0001) and NAC + Pb groups (p < 0.0001) normalising them to Sham levels. These findings highlight LYC's therapeutic potential against malaria-related oxidative stress.},
}

Animals
*Lung/pathology/drug effects
Mice
Lycopene
*Brain/pathology/drug effects/metabolism
Plasmodium berghei
*Malaria/drug therapy/pathology
*Antioxidants/administration & dosage
*Oxidative Stress/drug effects
*Reactive Oxygen Species/metabolism
*Carotenoids/administration & dosage
*Reactive Nitrogen Species/metabolism
Thiobarbituric Acid Reactive Substances/analysis
Male
Nitric Oxide/analysis
Female
Disease Models, Animal

@article {pmid40846701,
year = {2025},
author = {Musillo, C and Samà, M and Creutzberg, KC and Begni, V and Collacchi, B and Bitraj, J and Collo, G and Riva, MA and Berry, A and Cirulli, F},
title = {Sex-dependent preventive effects of prenatal N-acetyl-cysteine on neuronal, emotional and metabolic dysfunctions following exposure to maternal high-fat diet in mice.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {306},
pmid = {40846701},
issn = {2158-3188},
mesh = {Animals ; Female ; *Diet, High-Fat/adverse effects ; Mice ; Pregnancy ; *Prenatal Exposure Delayed Effects/prevention & control/metabolism ; *Acetylcysteine/pharmacology/administration & dosage ; Male ; Humans ; Neurons/drug effects/metabolism ; Neuronal Plasticity/drug effects ; Hippocampus/metabolism/drug effects ; Anxiety/prevention & control ; Disease Models, Animal ; Behavior, Animal/drug effects ; *Cognitive Dysfunction/prevention & control ; Sex Factors ; Mice, Inbred C57BL ; },
abstract = {While a clear association between maternal obesity and an increased risk for neuropsychiatric disorders in the offspring has been described, the underlying mechanisms remain poorly understood. We hypothesised that a maternal high-fat diet (mHFD) would act as a stressor, increasing glucocorticoids, resulting in an altered redox balance and disrupted neuronal plasticity of the limbic system. Such enduring effects would impair the emotional and cognitive profile, neuroendocrine responses, and metabolic and redox homeostasis in the adult offspring. We utilised a mouse model and a translational cellular model employing human neurons derived from inducible Pluripotent Stem Cells (iPSCs) to evaluate the impact of mHFD on neurodevelopment and to test the protection afforded by the antioxidant N-acetyl-cysteine (NAC). Our approach combined behavioural and metabolic phenotyping, biochemical assays, morphological assessment, and targeted gene expression analysis. Results indicate that prenatal administration of NAC prevented anxiety-like and risk-taking behaviours, cognitive impairments and metabolic alterations in mHFD adult mouse offspring, particularly in females. These changes were accompanied by hippocampal downregulation of genes involved in neuronal plasticity, such as BDNF. Using human neurons in vitro, pre-treatment with NAC rescued the negative effects of glucocorticoids on neuronal plasticity via a BDNF-mediated mechanism. The protective effects of NAC over mHFD in females suggest that rebalancing the redox status could be exploited as an overall strategy to buffer the negative effects of early adversities on neurodevelopment.},
}

Animals
Female
*Diet, High-Fat/adverse effects
Mice
Pregnancy
*Prenatal Exposure Delayed Effects/prevention & control/metabolism
*Acetylcysteine/pharmacology/administration & dosage
Male
Humans
Neurons/drug effects/metabolism
Neuronal Plasticity/drug effects
Hippocampus/metabolism/drug effects
Anxiety/prevention & control
Disease Models, Animal
Behavior, Animal/drug effects
*Cognitive Dysfunction/prevention & control
Sex Factors
Mice, Inbred C57BL

@article {pmid40842893,
year = {2025},
author = {Yelleti, G and Aroor, AR and Shenoy, RP and Karmakar, A and Rao, A and Lewis, CR and Asok, A and Maripini, N and Biswas, M and Varier, V and Roy, A and Suryakanth, VB},
title = {Potential Effects of Selenium and N-Acetylcysteine Supplementation in Ameliorating Cardinal Symptoms of Nω-Nitro-L-Arginine Methyl Ester Hydrochloride (L-NAME) Induced Preeclampsia in Wistar Rats.},
journal = {Reports of biochemistry & molecular biology},
volume = {13},
number = {4},
pages = {495-506},
pmid = {40842893},
issn = {2322-3480},
abstract = {BACKGROUND: Preeclampsia (PE) is a hypertensive disorder in pregnancy affecting multiple organ systems. This study hypothesized that oxidative stress and inflammatory responses contribute to the pathogenesis of Preeclampsia, and that selenium and N-acetylcysteine (NAC) could mitigate these effects.

METHODS: The study was initiated after approval from the Institutional Animal Ethics Committee. Twenty-four female Wistar rats were divided equally into four groups. Group I served as controls, while Groups II, III, and IV received Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) to induce hypertension from day 10 to 20 of gestation. Additionally, Group III received selenium (240 μg/kg/day) and Group IV received NAC (160 mg/kg). On day 20, Blood Pressure (BP) monitoring and urine protein estimation were carried out to assess hypertension and proteinuria, while blood samples were collected to measure malondialdehyde (MDA) and interleukin-6 (IL-6) levels, as markers of oxidative stress and inflammation, respectively. Statistical analysis was performed using GraphPad Prism 10.2.

RESULTS: Selenium improved L-NAME-induced hypertension (Mean BP 107.63±5.22 mmHg vs 140.9±8.38 mmHg in disease control (DC) and proteinuria (65.5±4.09 vs 140.2±11.85 mg/day in DC) and significantly reduced the inflammatory response (IL-6 23.4±1.06 vs 50.63±3.35 pg/mL in DC) but had little effect on oxidative stress (MDA 0.21±0.02 vs 0.24±0.02 nmol/mL in DC). NAC did not lower BP (Mean BP 129.33±7.96 mmHg) but significantly reduced proteinuria (92.7±6.37mg/day), IL-6 levels (18.24±0.42 pg/mL), and oxidative stress (MDA 0.16±0.01 nmol/mL).

CONCLUSIONS: These findings suggest that selenium and NAC play distinct protective roles in the pathophysiology of preeclampsia, potentially offering synergistic effects for cardiovascular and kidney health in hypertensive pregnancies.},
}

@article {pmid40834985,
year = {2025},
author = {Ghosh, C and Khaket, TP and Gunda, V and Yang, Z and Hu, J and Alamaw, ED and Zhang, L and Zhang, YQ and Shen, M and Tabdili, Y and Boufraqech, M and Kassu, R and Kebebew, E},
title = {Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in anaplastic thyroid cancer through enhanced activation of oxidative stress that leads to apoptosis.},
journal = {Cancer letters},
volume = {},
number = {},
pages = {217990},
doi = {10.1016/j.canlet.2025.217990},
pmid = {40834985},
issn = {1872-7980},
abstract = {Anaplastic thyroid cancer (ATC) has one of the highest mortality rates of all human malignancies and has no cure. We used combination drug matrix screening of highly active compounds and identified that combination of nitazoxanide and auranofin was one of those with the highest synergistic anticancer activity. We investigated its synergistic anticancer activity and mechanism of action in preclinical ATC models. We performed in vitro, ex vivo, and in vivo ATC models to evaluate the synergistic anticancer activity and the mechanism of action of this combination. Combination nitazoxanide and auranofin treatment synergistically inhibited cellular proliferation, colony formation, and cellular migration compared to control and single agents. Combination treatment also significantly reduced ATC cell line and patient-derived ATC spheroid size. Nitazoxanide alone and in combination with auranofin caused ER stress and apoptosis. Auranofin alone and in combination with nitazoxanide induced activation of the ROS generating pathway. This led to enhanced increase in ROS and MDA levels with combination treatment associated with upregulation of HMOX-1 and cell death that was reversed by N-acetyl cysteine (NAC). The combination significantly inhibited tumor growth in vivo in 8505C ATC cells, and C643 ATC cells, without significant treatment-related toxicity. Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in vitro, ex vivo, and in vivo in ATC, which is due to enhanced oxidative stress and induction of apoptosis compared to single-drug treatment. Both drugs are FDA approved; their combination is a potential candidate for evaluation in a clinical trial for ATC therapy.},
}

@article {pmid40834757,
year = {2025},
author = {Li, C and Yang, J and Cao, L and Yan, A and Zhang, X and Duan, J and Yu, X and Wang, D and Wang, X and Li, C},
title = {Hexafluoropropylene oxide dimer acid (GenX) induces apoptosis in primary cortical neurons via stimulating ROS production and NF-κB activation.},
journal = {Ecotoxicology and environmental safety},
volume = {303},
number = {},
pages = {118873},
doi = {10.1016/j.ecoenv.2025.118873},
pmid = {40834757},
issn = {1090-2414},
abstract = {Hexafluoropropylene oxide dimer acid (HFPO-DA), commonly known as GenX, is a replacement for perfluorooctanoic acid (PFOA) which readily accumulates in the brain and exhibits neurotoxic effects. However, the adverse impacts of GenX on neurons and its underlying mechanisms remain poorly understood. In this study, primary cortical neurons isolated from neonatal mice were exposed to varying concentrations of GenX to assess cell viability, intracellular reactive oxygen species (ROS) levels, and morphological alterations. Additionally, the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, NF-κB, and Tomm20 was examined. The results showed that increasing concentrations of GenX significantly elevated intracellular ROS levels and markedly reduced cell viability and the number of cells. Neuronal morphology was severely disrupted, characterized by decreased neurite branching, shortened neurite length, and reduced soma size. At 200 μM and 400 μM GenX, apoptosis rates were dramatically increased (p < 0.0001), accompanied by a pronounced increase in NF-κB fluorescence intensity and nuclear translocation. Western blot analysis further revealed a progressive downregulation of Bcl-2 and Tomm20, while levels of Bax, Cleaved Caspase-3/Caspase-3 increased in a dose-dependent manner. Notably, pretreatment with N-Acetylcysteine (NAC) effectively reversed GenX-induced ROS accumulation (p = 0.0001), NF-κB activation, and neuronal apoptosis. Collectively, these findings demonstrate that GenX exposure induces ROS accumulation in primary cortical neurons, leading to apoptosis through mitochondrial dysfunction mediated by Tomm20 downregulation and the activation of Caspase-3 and NF-κB. This study provides novel mechanistic insights into the neurotoxicity of the emerging environmental contaminant GenX and offers a theoretical basis for developing neuroprotective targets against such exposures.},
}

@article {pmid40834221,
year = {2025},
author = {Zanesco, MC and Yoshitani, MM and Fagundes, FL and Campos, FG and Pereira, PP and Pereira, QC and Pereira, JA and Santos, RC and Martinez, CAR},
title = {Enemas with sucralfate and n-acetylcysteine can reduce inflammation and oxidative stress in colonic mucosa without fecal stream.},
journal = {Acta cirurgica brasileira},
volume = {40},
number = {},
pages = {e406325},
doi = {10.1590/acb406325},
pmid = {40834221},
issn = {1678-2674},
mesh = {Animals ; *Acetylcysteine/administration & dosage/pharmacology ; *Oxidative Stress/drug effects ; *Sucralfate/administration & dosage/pharmacology ; *Intestinal Mucosa/drug effects/pathology ; Male ; *Enema/methods ; Colon/drug effects/pathology ; Rats, Wistar ; *Colitis/drug therapy/pathology ; Malondialdehyde/analysis ; Rats ; Inflammation/drug therapy ; Disease Models, Animal ; Peroxidase/analysis ; Reproducibility of Results ; *Anti-Ulcer Agents/administration & dosage ; Antioxidants ; Superoxide Dismutase/analysis ; Glutathione/analysis ; Treatment Outcome ; },
abstract = {PURPOSE: To evaluate whether enemas containing sucralfate (SCF) alone or in combination with n-acetylcysteine (NAC) reduces inflammation and oxidative stress (OS) in the colonic mucosa without fecal stream.

METHODS: Forty-eight rats were subjected to left colostomy and distal rectal mucous fistula. During the procedure, 2 cm of the colon was collected to constitute the sham group. Twelve weeks after the surgical procedure, the animals were divided into two groups (n = 24) and received daily enemas containing saline, SCF (2 g/kg), NAC (100 mg/kg), or SCF + NAC (2 g/kg + 100 mg/kg, respectively) for two or four weeks. At the end of the intervention period, the animals were euthanized, and colonic segments without fecal stream were removed for histological and biochemical analyses. The diagnosis of colitis was made by histological analysis, and the inflammatory score was assessed using a validated scale. The neutrophilic infiltrate was evaluated by quantifying the content of myeloperoxidase (MPO) in the tissue. OS was determined by evaluating the activity of colonic antioxidant systems (superoxide dismutase, catalase, and reduced glutathione) and malondialdehyde (MDA) levels. The differences among subgroups were analyzed with the Mann-Whitney's test, whereas changes over time were analyzed via the Kruskal-Wallis' test, with the significance level of 5% (p < 0.05).

RESULTS: Enemas with SCF and NAC alone or in combination reduced colonic inflammation and the tissue levels of MPO and MDA and increased the levels of antioxidant enzymes.

CONCLUSION: SCF and NAC enemas alone or in combination reduced inflammation activity and OS in colon segments without fecal stream.},
}

Animals
*Acetylcysteine/administration & dosage/pharmacology
*Oxidative Stress/drug effects
*Sucralfate/administration & dosage/pharmacology
*Intestinal Mucosa/drug effects/pathology
Male
*Enema/methods
Colon/drug effects/pathology
Rats, Wistar
*Colitis/drug therapy/pathology
Malondialdehyde/analysis
Rats
Inflammation/drug therapy
Disease Models, Animal
Peroxidase/analysis
Reproducibility of Results
*Anti-Ulcer Agents/administration & dosage
Antioxidants
Superoxide Dismutase/analysis
Glutathione/analysis
Treatment Outcome

@article {pmid40833873,
year = {2025},
author = {Sato, Y and Tanaka, M and Kitamura, N and Araki, N and Kurata, W and Sasaki, A and Seo, Y and Kuribayashi, K and Kobayashi, S and Niitsu, Y},
title = {ROS-Driven PKCζ Signaling as a Widely Involved Mechanism for Cancer Cell Motility and Metastasis.},
journal = {Cancer science},
volume = {},
number = {},
pages = {},
doi = {10.1111/cas.70165},
pmid = {40833873},
issn = {1349-7006},
abstract = {The enhancement of cell motility by bioactive molecules such as growth factors, hormones, and tissue factors is pivotal in cancer invasion and metastasis. However, the molecular mechanisms underlying this enhancement remain incompletely understood. In this study, we demonstrate that hepatoblastoma HepG2 cell motility is significantly increased following hepatocyte growth factor (HGF) treatment, as assessed by phagokinetic track assays, Transwell assays, and scratch assays. This enhancement is mediated by reactive oxygen species (ROS), which activate the PKCζ/Rho GTPase signaling pathway. Notably, the motility increase is markedly suppressed by superoxide dismutase (SOD), N-acetylcysteine (NAC), diphenyleneiodonium (DPI), and the PKCζ inhibitory peptide MyrPKCζ. Similar patterns of motility enhancement and its inhibition by MyrPKCζ were observed in HGF-treated colon cancer HCT116 cells, epidermal growth factor (EGF)-treated HepG2 and HCT116 cells, and transforming growth factor-β (TGF-β)-treated HepG2 cells, as evaluated using Transwell assays. Additionally, estradiol enhances the motility of breast cancer MDA-MB-231-luc cells via ROS generation and activation of the PKCζ/Rho GTPase signaling pathway, with this effect significantly suppressed by MyrPKCζ in Transwell assays. The inhibitory effect of MyrPKCζ was further confirmed in vivo, where it suppressed peritoneal invasion of HCT116 cells in NOD-SCID mice. Furthermore, in NOD-SCID mice injected with MDA-MB-231-luc cells carrying shRNA targeting PKCζ into the tail vein, doxycycline-induced shRNA expression resulted in marked suppression of pulmonary metastasis. These findings indicate that the ROS/PKCζ/Rho GTPase signaling cascade is a pivotal regulator of cancer cell motility and suggest that PKCζ represents a promising therapeutic target for preventing cancer invasion and metastasis.},
}

@article {pmid40828450,
year = {2025},
author = {Mundassery, AI and Latha, RR and Kulangara, V and Mampilli, P and Chitharalil, BK and Abbdulkhaderkunju, J and Meleppat, DP},
title = {Effect of N-Acetylcysteine on Oxidative Stress and Hematological Recovery in Dogs with Babesia Gibsoni Infection.},
journal = {Acta parasitologica},
volume = {70},
number = {5},
pages = {186},
pmid = {40828450},
issn = {1896-1851},
abstract = {Babesia gibsoni infection in dogs causes hemolytic anemia, thrombocytopenia, and systemic inflammation, with many cases progressing to chronic or relapsing forms due to persistent parasitemia and oxidative stress. This study evaluated the clinical, hematobiochemical, and oxidative changes associated with B. gibsoni infection and assessed the therapeutic benefit of N-acetylcysteine (NAC) as an adjunct to triple therapy. Nineteen dogs confirmed positive for B. gibsoni via blood smear and PCR were identified; however, only twelve Labrador Retrievers of similar age (2-3 years) were enrolled for treatment to minimize variability in breed and age. The remaining dogs were excluded due to different breeds or incomplete treatment. Six healthy controls were also included. Infected animals exhibited significant alterations in leukocyte count, erythrocyte indices, platelet count, and urinary protein-to-creatinine ratio (UPC) compared to healthy controls, indicating systemic inflammation and renal involvement. Twelve infected dogs were randomly assigned to two groups: Group I received the triple therapy (doxycycline, clindamycin, metronidazole), while Group II received the same treatment with oral NAC (70 mg/kg for 5 days). Clinical, hematological, biochemical, and oxidative stress parameters were reassessed on Day 21. Both groups showed improvement post-treatment; however, Group II demonstrated greater recovery, including higher RBC counts, hemoglobin levels, platelet counts, and serum antioxidant capacity, along with reduced bilirubin and UPC levels. Mann-Whitney U test on Day 21 revealed significant improvements in serum antioxidant activity and mean corpuscular hemoglobin concentration (MCHC) in Group II (p < 0.05). Although other parameters did not reach statistical significance, several showed favorable trends toward improvement in the NAC group. These findings suggest that NAC supplementation enhances hematological recovery, reduces oxidative stress, and supports renal function in dogs with babesiosis. Given its favorable impact, NAC may serve as a valuable adjunct in managing canine babesiosis, particularly in cases with suspected or confirmed oxidative injury. Further studies with larger sample sizes are recommended.},
}

@article {pmid40827188,
year = {2025},
author = {Agrawal, A and Chowdhury, M and Winkie, C and Vijay, C},
title = {A Case of Acetaminophen Toxicity in a Patient With an Unusual Alpha-1 Antitrypsin Phenotype.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88224},
pmid = {40827188},
issn = {2168-8184},
abstract = {Acetaminophen is a commonly used over-the-counter analgesic and antipyretic that can be hepatotoxic if taken in excess. We present a case of acetaminophen-mediated hepatotoxicity following ingestion of a non-toxic dose of acetaminophen in a 16-year-old male with short bowel syndrome and a remote history of severe liver dysfunction with a rare alpha-1 antitrypsin phenotype Pi*EM. The patient initially presented with nonspecific symptoms of abdominal pain, nausea, vomiting, and diarrhea. N-acetylcysteine (NAC) therapy was initiated for acetaminophen toxicity. We suspect that the patient's susceptibility to acetaminophen-induced liver injury was likely due to underlying intestinal failure-associated liver disease that occurred as a child, as well as the Pi*EM, making the liver more prone to insults. This case highlights the importance of prompt recognition and management of acetaminophen toxicity in patients with prior liver disease, even if the amount ingested is thought to be non-toxic. In addition, the case highlights that rare alpha-1 antitrypsin phenotypes should be treated with heightened caution for liver dysfunction, as there is limited literature indicating if these phenotypes are pathogenic or non-pathogenic.},
}

@article {pmid40823012,
year = {2025},
author = {Bi, X and Huang, X and Zhang, C and Zhao, X and Ma, J and Li, M and Li, X and Zeng, B and Li, R and Zhang, X and Ya, F},
title = {Sulforaphane attenuates aldose reductase-mediated platelet dysfunction in high glucose-stimulated human platelets via downregulation of the Src/ROS/p53 signaling pathway.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1663245},
pmid = {40823012},
issn = {2296-861X},
abstract = {BACKGROUND: Platelet abnormalities are well-recognized complications of type 2 diabetes mellitus (T2DM). High glucose (HG) increases platelet mitochondrial dysfunction, apoptosis and hyperreactivity in T2DM, which underlie the occurrence of thrombotic events. Sulforaphane (SFN) is a dietary isothiocyanate enriched in cruciferous vegetables and possesses multiple biological activities. This study aimed to explore the efficacy of SFN on platelet dysfunction in HG-stimulated human platelets in vitro.

METHODS: Washed human platelets from healthy donors were pre-incubated with SFN (5, 10, or 20 μM) or vehicle control (0.05% DMSO) for 40 min at 37°C, with or without pharmacologic inhibitors (apalrestat, PP2, N-acetyl-cysteine, pifithrin-μ). Platelets were then stimulated with normal glucose (NG, 5 mM) or HG (25 mM) for an additional 90 min. Functional assays were performed to evaluate SFN efficacy and investigate its underlying mechanisms.

RESULTS: The results demonstrated that SFN attenuated HG-induced platelet dysfunction by alleviating mitochondrial dysfunction (manifested as loss of mitochondrial membrane potential; p < 0.001), apoptosis (characterized by increased caspase-9/-3 activation and phosphatidylserine exposure; p < 0.01), and hyperreactivity (evidenced by enhanced aggregation and activation; p < 0.05). Mechanistically, SFN significantly suppressed HG-induced aldose reductase (AR) activity (p < 0.001). Pharmacological inhibition revealed that the beneficial effects of SFN on platelet function were mediated mechanistically through AR downregulation, which attenuated p53 phosphorylation via Src-dependent ROS generation.

CONCLUSION: These findings suggest that by inhibiting the Src/ROS/p53 signaling pathway and mitigating AR-mediated platelet dysfunction, SFN may confer significant protection against atherothrombosis during hyperglycemia.},
}

@article {pmid40803576,
year = {2025},
author = {Aithal, GP},
title = {From Long to Snappy and Short Regimens for Paracetamol Overdose: Reinventing the N-Acetyl Cysteine Wheel.},
journal = {Journal of hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhep.2025.07.032},
pmid = {40803576},
issn = {1600-0641},
}

@article {pmid40706520,
year = {2025},
author = {Zhang, SF and Li, N and Liu, DL and Li, YH and Yang, Y and Ma, Y and Wang, YQ and Ma, Y and Luan, ZJ},
title = {Yttrium nitrate activates the oxidative stress-mediated NF-κB pathway to induce testicular inflammatory response and reduce sperm quality in mice.},
journal = {Ecotoxicology and environmental safety},
volume = {302},
number = {},
pages = {118720},
doi = {10.1016/j.ecoenv.2025.118720},
pmid = {40706520},
issn = {1090-2414},
abstract = {The rising environmental levels of yttrium have sparked concerns regarding its possible health hazards. Nevertheless, limited toxicological data are available to determine yttrium's toxicity and potential mechanisms on sperm. In our research, the action of oxidative stress and the NF-κB pathway on decreased sperm quality and testicular inflammatory reaction induced by yttrium exposure was analyzed. Yttrium nitrate (YN), N-Acetyl Cysteine (NAC), and JSH-23 were used to intervene in mice and cells in vivo and in vitro experiments. Eosin-nigrosine staining, in vitro fertilization, Annexin V-FITC/PI staining, ICP-MS, Hematoxylin-eosin staining, RT-qPCR, DCFH-DA staining, biochemical methods, ELISA, and western blot were applied to detect sperm motility, fertilizing capacity, apoptosis, Y[3+] accumulation, testicular structure, testicular function, and NF-κB gene expression, ROS, MDA, GSH, pro-inflammatory cytokines, and NF-κB protein expression, respectively. The results revealed that YN exposure reduced sperm motility, increased sperm apoptosis, disrupted testicular tissue structure and function in mice. Exposure to YN increased ROS content and NF-κB pathway activation in testicular tissue and cells, resulting in upregulation of pro-inflammatory cytokines in the testis. When NAC scavenged ROS, the YN-induced sperm damage and inflammatory reaction, and NF-κB pathway abnormal activation in the testis of mice were alleviated. In addition, sperm damage and testicular inflammatory reaction caused by YN were alleviated after blocking the NF-κB pathway with JSH-23 treatment. Our present study elucidated that YN could damage sperm quality and induce testicular inflammatory reaction, establishing YN's toxicological impact on the male reproductive system.},
}

@article {pmid40614987,
year = {2025},
author = {Ghosh, M and Viswaroopan, N and Kshirsagar, SM and Khan, J and Mohiuddin, S and Srivastava, RK and Athar, M and Banga, AK},
title = {Sustained delivery of 4-phenylbutyric acid via chitosan nanoparticles in foam for decontamination and treatment of lewisite-mediated skin injury.},
journal = {International journal of pharmaceutics},
volume = {682},
number = {},
pages = {125928},
doi = {10.1016/j.ijpharm.2025.125928},
pmid = {40614987},
issn = {1873-3476},
mesh = {*Chitosan/chemistry/administration & dosage ; Animals ; *Phenylbutyrates/administration & dosage/chemistry/pharmacokinetics ; *Nanoparticles/chemistry/administration & dosage ; Skin/drug effects/metabolism ; Mice ; Delayed-Action Preparations/administration & dosage ; Skin Absorption/drug effects ; Humans ; Drug Liberation ; Decontamination/methods ; Administration, Cutaneous ; Particle Size ; Chemical Warfare Agents/toxicity ; Mice, Hairless ; Drug Carriers/chemistry ; },
abstract = {Lewisite, a chemical warfare agent, induces severe skin injury by oxidative stress and endoplasmic reticulum (ER) dysfunction, necessitating innovative antidote strategies. This study developed chitosan nanoparticle-loaded foam formulations for rapid skin decontamination and sustained topical delivery of 4-phenylbutyric acid (4-PBA), an ER stress-reducing chaperone. Nanoparticles were synthesized via ionic gelation using low (LMW) and medium molecular weight (MMW) chitosan. The optimized formulations, N31 (LMW) and N35 (MMW), achieved drug loadings of 5.04 % and 10.09 % w/w, particle sizes of 141.88 ± 26.31 nm and 176.10 ± 36.97 nm, monodisperse distributions (PDI < 0.3), high entrapment efficiency (>93 %) and good stability with zeta potential of -16.67 mV and -19.37 mV, respectively. Incorporation into foam enabled both effective decontamination (>70 % efficiency) and sustained 4-PBA delivery. In vitro release studies demonstrated sustained drug release over 24 h. Permeation studies using dermatomed human skin revealed that nanoparticle formulations significantly reduced 4-PBA delivery: N35 decreased permeation by 38.4 % (214.35 ± 16.6 µg/cm[2] vs. 348.10 ± 5.37 µg/cm[2] for free 4-PBA), while N31 reduced it by 81.35 % (64.90 ± 6.89 µg/cm[2]). Both formulations retained efficacy in PAO challenged skin, with N35 delivering 158.54 ± 53.93 µg/cm[2] and N31 138.25 ± 14.72 µg/cm[2] over 24 h. Furthermore, in vivo studies showed that the optimized formulation with N35 chitosan (4-PBA N35 + N-acetyl cysteine (NAC)) significantly protects against PAO-induced skin injury and inflammatory cytokine production in Ptch1+/-/SKH-1 hairless mice. Thus, the translational feasibility and effective treatment by the foam formulated 4-PBA N35 + NAC against arsenical-induced skin injury is demonstrated.},
}

*Chitosan/chemistry/administration & dosage
Animals
*Phenylbutyrates/administration & dosage/chemistry/pharmacokinetics
*Nanoparticles/chemistry/administration & dosage
Skin/drug effects/metabolism
Mice
Delayed-Action Preparations/administration & dosage
Skin Absorption/drug effects
Humans
Drug Liberation
Decontamination/methods
Administration, Cutaneous
Particle Size
Chemical Warfare Agents/toxicity
Mice, Hairless
Drug Carriers/chemistry

@article {pmid40583489,
year = {2025},
author = {Niu, C and Li, RT and Hao, XS and Qi, X and Wang, FZ and Fei, HR},
title = {Scutebarbatine B Exerts Anti-Breast Cancer Activity by Inducing Cell Cycle Arrest and Apoptosis Through Multiple Pathways.},
journal = {Phytotherapy research : PTR},
volume = {39},
number = {8},
pages = {3432-3449},
doi = {10.1002/ptr.70007},
pmid = {40583489},
issn = {1099-1573},
support = {ZR2022MH178//Shandong Provincial Natural Science Foundation, China/ ; ZR2022MH178//Shandong ProvincialNatural Science Foundation, China/ ; },
mesh = {*Apoptosis/drug effects ; Humans ; Female ; Animals ; *Breast Neoplasms/drug therapy/pathology ; *Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Mice ; Reactive Oxygen Species/metabolism ; Xenograft Model Antitumor Assays ; *Scutellaria/chemistry ; Signal Transduction/drug effects ; Cell Proliferation/drug effects ; Mice, Inbred BALB C ; *Diterpenes/pharmacology ; *Antineoplastic Agents, Phytogenic/pharmacology ; DNA Damage/drug effects ; Mice, Nude ; Cyclin B1/metabolism ; Cell Survival/drug effects ; MCF-7 Cells ; },
abstract = {Breast cancer is the most commonly occurring cancer among women with high mortality. Identifying effective anticancer compounds to improve the overall survival is imperative. The present study was designed to evaluate the effects and underlying mechanisms of Scutebarbatine B (SBT-B), a diterpenoid alkaloid extracted from Scutellaria barbata D. Don (S. barbata), on breast cancer. Cell viability assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, immunofluorescence, flow cytometry analysis, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, Western blot analysis, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and dihydroethidium (DHE) staining were performed to elucidate the anticancer mechanisms of SBT-B in vitro. Mice xenograft models were used to assess the anticancer properties in vivo. We demonstrated that SBT-B suppressed the proliferation of breast cancer cells in a dose-dependent manner. SBT-B treatment induced DNA damage response, G2/M phase arrest and downregulated the expression of cyclinB1, cyclinD1, Cdc2, and p-Cdc2. SBT-B could trigger apoptosis through increasing the cleavage of caspase-8, caspase-9 and PARP in breast cancer cells. Additionally, SBT-B elevated the generation of intracellular reactive oxygen species (ROS). Treatment with a ROS scavenger N-acetyl cysteine (NAC) partially blocked viability reduction and cleavage of caspase-8 and PARP induced by SBT-B. Moreover, SBT-B blocked pRB/E2F1 and Akt/mTOR pathways. Incubation with SBT-B increased the expression of IRE1 and phospho-JNK. In vivo, SBT-B exhibited significant suppression of tumor growth in xenograft models. We demonstrate firstly that SBT-B induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells. ROS generation, suppression of oncogenic signaling and activation of IRE1/JNK pathway play an essential role in the anticancer activity of SBT-B. Our study highlights the potential of SBT-B as an alternative candidate to treat human breast cancer.},
}

*Apoptosis/drug effects
Humans
Female
Animals
*Breast Neoplasms/drug therapy/pathology
*Cell Cycle Checkpoints/drug effects
Cell Line, Tumor
Mice
Reactive Oxygen Species/metabolism
Xenograft Model Antitumor Assays
*Scutellaria/chemistry
Signal Transduction/drug effects
Cell Proliferation/drug effects
Mice, Inbred BALB C
*Diterpenes/pharmacology
*Antineoplastic Agents, Phytogenic/pharmacology
DNA Damage/drug effects
Mice, Nude
Cyclin B1/metabolism
Cell Survival/drug effects
MCF-7 Cells

@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 = {24},
number = {8},
pages = {e70100},
pmid = {40398422},
issn = {1474-9726},
support = {P01 AG052359/AG/NIA NIH HHS/United States ; P30 CA023074/CA/NCI NIH HHS/United States ; //Bowman Professorship in Medical Sciences/ ; },
mesh = {*Oxidative Stress ; Animals ; *Mitochondria/metabolism/drug effects/pathology ; *Stromal Cells/metabolism ; *Lymph Nodes/metabolism/cytology/pathology/immunology ; Mice ; Reactive Oxygen Species/metabolism ; *Homeostasis ; *Aging ; *T-Lymphocytes/metabolism/immunology ; Mice, Inbred C57BL ; },
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.},
}

*Oxidative Stress
Animals
*Mitochondria/metabolism/drug effects/pathology
*Stromal Cells/metabolism
*Lymph Nodes/metabolism/cytology/pathology/immunology
Mice
Reactive Oxygen Species/metabolism
*Homeostasis
*Aging
*T-Lymphocytes/metabolism/immunology
Mice, Inbred C57BL

@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 = {},
pmid = {40318637},
issn = {1878-1551},
support = {R01 CA289703/CA/NCI NIH HHS/United States ; DP2 CA258224/CA/NCI NIH HHS/United States ; R01 DK093399/DK/NIDDK NIH HHS/United States ; R01 DK116079/DK/NIDDK NIH HHS/United States ; R01 DK126887/DK/NIDDK NIH HHS/United States ; R35 GM119768/GM/NIGMS NIH HHS/United States ; },
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 {pmid39983406,
year = {2025},
author = {Zhang, C and Peng, S and Zheng, Z and Chen, Z and Li, M and Huang, N and Liu, Z and Yang, MX and Chen, H},
title = {Novel bis-pocket binding aldose reductase inhibitors sensitize MCF-7/ADR cells to doxorubicin in a dual-role manner.},
journal = {Bioorganic chemistry},
volume = {157},
number = {},
pages = {108286},
doi = {10.1016/j.bioorg.2025.108286},
pmid = {39983406},
issn = {1090-2120},
mesh = {Humans ; *Aldehyde Reductase/antagonists & inhibitors/metabolism ; *Doxorubicin/pharmacology/chemistry ; Structure-Activity Relationship ; Molecular Structure ; *Drug Screening Assays, Antitumor ; *Cell Proliferation/drug effects ; *Dose-Response Relationship, Drug ; *Enzyme Inhibitors/pharmacology/chemistry/chemical synthesis ; MCF-7 Cells ; Antibiotics, Antineoplastic/pharmacology/chemistry/chemical synthesis ; Drug Resistance, Neoplasm/drug effects ; Antineoplastic Agents/pharmacology/chemistry/chemical synthesis ; },
abstract = {Multidrug resistance (MDR) represents a bottleneck in the treatment of breast cancer. Although the potential of aldose reductase inhibitors (ARIs) as sensitizers against MDR has been explored in recent decades, the intrinsic mechanism still needs to be elucidated, and promising agents in the clinic need to be developed. In this study, three novel ARIs (5a-c), characterized by bis-pocket binding, were designed and synthesized. Inhibitory activity is positively correlated with antioxidation and benefits from rigid spacers. Only 5a with less activities in inhibition and antioxidation was demonstrated as a stronger sensitizer against doxorubicin (DOX)-resistant MCF-7 cells (MCF-7/ADR) than epalrestat (EPA). Either 5a or EPA may decrease GSH abundance and increase ROS, Fe[2+], and lipid peroxidation levels. The restorative effects of both ARIs may be blocked by N-acetyl cysteine (NAC). These data suggest that both 5a and EPA may restore the sensitivity of MCF-7/ADR cells to DOX by increasing ferroptosis activity. Furthermore, the inhibition of AKR1B1 by 5a, as well as by EPA, dramatically decreased both p-STAT3 and SLC7A11 expression. Gene knockdown of AKR1B1 has the same effects as AKR1B1 inhibition. This evidence indicates that both ARIs can suppress MCF-7/ADR cell growth via the upregulation of ferroptosis activity via the AKR1B1/STAT3/SLC7A11 axis. Additionally, 5a was found to increase the accumulation of intramolecular DOX by inhibiting ABCB1, but EPA did not. These results support that 5a is a promising sensitizing agent against multidrug resistance in breast cancer.},
}

Humans
*Aldehyde Reductase/antagonists & inhibitors/metabolism
*Doxorubicin/pharmacology/chemistry
Structure-Activity Relationship
Molecular Structure
*Drug Screening Assays, Antitumor
*Cell Proliferation/drug effects
*Dose-Response Relationship, Drug
*Enzyme Inhibitors/pharmacology/chemistry/chemical synthesis
MCF-7 Cells
Antibiotics, Antineoplastic/pharmacology/chemistry/chemical synthesis
Drug Resistance, Neoplasm/drug effects
Antineoplastic Agents/pharmacology/chemistry/chemical synthesis

@article {pmid37537647,
year = {2023},
author = {Refsnes, M and Skuland, T and Jørgensen, R and Sæter-Grytting, V and Snilsberg, B and Øvrevik, J and Holme, JA and Låg, M},
title = {Role of different mechanisms in pro-inflammatory responses triggered by traffic-derived particulate matter in human bronchiolar epithelial cells.},
journal = {Particle and fibre toxicology},
volume = {20},
number = {1},
pages = {31},
pmid = {37537647},
issn = {1743-8977},
mesh = {Humans ; *Particulate Matter/toxicity ; Reactive Oxygen Species/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Cyclooxygenase 2 ; Cytochrome P-450 CYP1A1/genetics ; Plasminogen Activator Inhibitor 2/metabolism/pharmacology ; Cytokines/metabolism ; Epithelial Cells ; Vehicle Emissions/toxicity ; *Air Pollutants/toxicity/metabolism ; },
abstract = {BACKGROUND: Traffic-derived particles are important contributors to the adverse health effects of ambient particulate matter (PM). In Nordic countries, mineral particles from road pavement and diesel exhaust particles (DEP) are important constituents of traffic-derived PM. In the present study we compared the pro-inflammatory responses of mineral particles and DEP to PM from two road tunnels, and examined the mechanisms involved.

METHODS: The pro-inflammatory potential of 100 µg/mL coarse (PM10-2.5), fine (PM2.5-0.18) and ultrafine PM (PM0.18) sampled in two road tunnels paved with different stone materials was assessed in human bronchial epithelial cells (HBEC3-KT), and compared to DEP and particles derived from the respective stone materials. Release of pro-inflammatory cytokines (CXCL8, IL-1α, IL-1β) was measured by ELISA, while the expression of genes related to inflammation (COX2, CXCL8, IL-1α, IL-1β, TNF-α), redox responses (HO-1) and metabolism (CYP1A1, CYP1B1, PAI-2) was determined by qPCR. The roles of the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) were examined by treatment with the AhR-inhibitor CH223191 and the anti-oxidant N-acetyl cysteine (NAC).

RESULTS: Road tunnel PM caused time-dependent increases in expression of CXCL8, COX2, IL-1α, IL-1β, TNF-α, COX2, PAI-2, CYP1A1, CYP1B1 and HO-1, with fine PM as more potent than coarse PM at early time-points. The stone particle samples and DEP induced lower cytokine release than all size-fractionated PM samples for one tunnel, and versus fine PM for the other tunnel. CH223191 partially reduced release and expression of IL-1α and CXCL8, and expression of COX2, for fine and coarse PM, depending on tunnel, response and time-point. Whereas expression of CYP1A1 was markedly reduced by CH223191, HO-1 expression was not affected. NAC reduced the release and expression of IL-1α and CXCL8, and COX2 expression, but augmented expression of CYP1A1 and HO-1.

CONCLUSIONS: The results indicate that the pro-inflammatory responses of road tunnel PM in HBEC3-KT cells are not attributed to the mineral particles or DEP alone. The pro-inflammatory responses seem to involve AhR-dependent mechanisms, suggesting a role for organic constituents. ROS-mediated mechanisms were also involved, probably through AhR-independent pathways. DEP may be a contributor to the AhR-dependent responses, although other sources may be of importance.},
}

Humans
*Particulate Matter/toxicity
Reactive Oxygen Species/metabolism
Tumor Necrosis Factor-alpha/metabolism
Cyclooxygenase 2
Cytochrome P-450 CYP1A1/genetics
Plasminogen Activator Inhibitor 2/metabolism/pharmacology
Cytokines/metabolism
Epithelial Cells
Vehicle Emissions/toxicity
*Air Pollutants/toxicity/metabolism

@article {pmid37075699,
year = {2023},
author = {Yap, YS and Hu, J},
title = {Exploiting metabolic vulnerabilities in breast cancers with NF1 loss.},
journal = {Cell reports. Medicine},
volume = {4},
number = {4},
pages = {101010},
pmid = {37075699},
issn = {2666-3791},
mesh = {Humans ; Female ; Neurofibromin 1/genetics/metabolism ; *Breast Neoplasms/drug therapy ; Phosphatidylinositol 3-Kinases/metabolism ; *Biochemical Phenomena ; },
abstract = {Auf der Maur et al.[1] identify neurofibromin 1 (NF1) loss as a mechanism of resistance to PI3K inhibitor in breast cancer cells. NF1 loss leads to enhanced glycolysis, which may be targeted with the antioxidant N-acetyl cysteine (NAC).},
}

Humans
Female
Neurofibromin 1/genetics/metabolism
*Breast Neoplasms/drug therapy
Phosphatidylinositol 3-Kinases/metabolism
*Biochemical Phenomena

@article {pmid35775164,
year = {2022},
author = {Tu, C and Lai, S and Huang, Z and Cai, G and Zhao, K and Gao, J and Wu, Z and Zhong, Z},
title = {Accumulation of advanced oxidation protein products contributes to age-related impairment of gap junction intercellular communication in osteocytes of male mice.},
journal = {Bone & joint research},
volume = {11},
number = {7},
pages = {413-425},
pmid = {35775164},
issn = {2046-3758},
abstract = {AIMS: Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes' GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes' GJIC in aged male mice and its mechanism.

METHODS: Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks.

RESULTS: The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes' GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo.

CONCLUSION: Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413-425.},
}

@article {pmid35629096,
year = {2022},
author = {Zisis, IE and Georgiadis, G and Docea, AO and Calina, D and Cercelaru, L and Tsiaoussis, J and Lazopoulos, G and Sofikitis, N and Tsatsakis, A and Mamoulakis, C},
title = {Renoprotective Effect of Vardenafil and Avanafil in Contrast-Induced Nephropathy: Emerging Evidence from an Animal Model.},
journal = {Journal of personalized medicine},
volume = {12},
number = {5},
pages = {},
pmid = {35629096},
issn = {2075-4426},
abstract = {The potential renoprotective effects of vardenafil (VAR) have been evaluated in a very limited number of studies using acute kidney injury animal models other than contrast-induced nephropathy (CIN) with promising results, while avanafil (AVA) has not been evaluated in this respect before. The purpose of this study was to evaluate for the first time the potential renoprotective effect of VAR and AVA in a rat model of CIN. Twenty-five male Wistar rats were equally assigned into five groups: control, CIN, CIN+N-acetyl cysteine (NAC) (100 mg/kg/day) as a positive control, CIN+VAR (10 mg/kg/day) and CIN+AVA (50 mg/kg/day). CIN was induced by dehydration, inhibition of prostaglandin and nitric oxide synthesis as well as exposure to the contrast medium (CM). Serum Cr (sCr) levels were measured at 24 and 48 h after CIN induction. At 48 h of CM exposure, animals were sacrificed. Matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, kidney injury molecule 1 (KIM-1) and cystatin-C (Cys-C) were measured on renal tissue. Histopathological findings were evaluated on kidney tissue. All treatment groups had close to normal kidney appearance. sCr levels subsided in all treatment groups compared to CIN group at 48 h following CIN induction. A significant decline in the levels of MMP-2, MMP-9, KIM-1 and Cys-C compared to CIN group was observed. These results provide emerging evidence that VAR and AVA may have the potential to prevent CIN.},
}

@article {pmid34499870,
year = {2021},
author = {Baron, JM and Heaney, DL and John, A and Fantz, CR},
title = {Real evidence to assess clinical testing interference risk (REACTIR): A strategy using real world data to assess the prevalence of interfering substances in patients undergoing clinical laboratory testing.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {523},
number = {},
pages = {178-184},
doi = {10.1016/j.cca.2021.09.001},
pmid = {34499870},
issn = {1873-3492},
mesh = {*Blood Glucose ; Humans ; Laboratories, Clinical ; *Point-of-Care Systems ; Point-of-Care Testing ; Prevalence ; },
abstract = {INTRODUCTION: Laboratory test interferences can cause spurious test results and patient harm. Knowing the frequency of various interfering substances in patient populations likely to be tested with a particular laboratory assay may inform test development, test utilization and strategies to mitigate interference risk.

METHODS: We developed REACTIR (Real Evidence to Assess Clinical Testing Interference Risk), an approach using real world data to assess the prevalence of various interfering substances in patients tested with a particular type of assay. REACTIR uses administrative real world data to identify and subgroup patient cohorts tested with a particular laboratory test and evaluate interference risk.

RESULTS: We demonstrate the application REACTIR to point of care (POC) blood glucose testing. We found that exposure to several substances with the potential to interfere in POC blood glucose tests, including N-acetyl cysteine (NAC) and high dose vitamin C was uncommon in most patients undergoing POC glucose tests with several key exceptions, such as burn patients receiving high dose IV-vitamin C or acetaminophen overdose patients receiving NAC.

CONCLUSIONS: Findings from REACTIR may support risk mitigation strategies including targeted clinician education and clinical decision support. Likewise, adaptations of REACTIR to premarket assay development may inform optimal assay design and assessment.},
}

*Blood Glucose
Humans
Laboratories, Clinical
*Point-of-Care Systems
Point-of-Care Testing
Prevalence

@article {pmid33553365,
year = {2021},
author = {Bai, L and Yu, E},
title = {A narrative review of risk factors and interventions for cancer-related cognitive impairment.},
journal = {Annals of translational medicine},
volume = {9},
number = {1},
pages = {72},
pmid = {33553365},
issn = {2305-5839},
abstract = {Cancer-related cognitive impairment (CRCI) refers to a series of cognitive impairment symptoms associated with alternations in brain structure and function, caused by a non-central nervous system malignant tumor and its related treatment. CRCI may present as memory loss, impaired concentration, difficulty in multitasking and word retrieval, and reduced comprehension speed. CRCI has become one of the prevalent factors that compromise the quality of life for cancer survivors. Different treatments, including surgery, chemotherapy, radiotherapy, endocrine therapy, and targeted drugs, may contribute to CRCI. Meanwhile, patients' factors, including emotional challenges and genetic makeup, also contribute to the development of CRCI. The condition can be treated with using stimulants methylphenidate and modafinil, metabolites of nicotine: cotinine, antidepressants of fluoxetine and fluvoxamine, dementia drug of donepezil, and antioxidants ZnSO4, n-acetyl cysteine, propofol, and Chinese herbal of silver leaf medicine. Psychotherapies, including meditation and relaxation, cognitive rehabilitation training, along with physical therapies, including aerobic exercise, resistance training, balance training, yoga, qigong, tai chi electroencephalogram biofeedback, and acupuncture, are also beneficial in alleviating cancer-related cognitive impairment symptoms. In recent years, researchers have focused on factors related to the condition and on the available interventions. However, most research was conducted independently, and no review has yet summarized the latest findings. This review details and discusses the status of related factors and potential treatments for CRCI. We also supply specific recommendations to facilitate future research and integration in this field.},
}

@article {pmid34909640,
year = {2020},
author = {Abdoli, N and Sadeghian, I and Mousavi, K and Azarpira, N and Ommati, MM and Heidari, R},
title = {Suppression of cirrhosis-related renal injury by N-acetyl cysteine.},
journal = {Current research in pharmacology and drug discovery},
volume = {1},
number = {},
pages = {30-38},
pmid = {34909640},
issn = {2590-2571},
abstract = {Cirrhosis-induced renal injury or cholemic nephropathy (CN) is a serious clinical complication with poor prognosis. CN could finally lead to renal failure and the need for organ transplantation. Unfortunately, there is no specific pharmacological intervention against CN to date. On the other hand, various studies mentioned the role of oxidative stress and mitochondrial impairment in the pathogenesis of CN. The current study aimed to evaluate the potential protective effects of NAC as a thiol-reducing agent and antioxidant in CN. Bile duct ligation (BDL) was used as a reliable animal model of cholestasis. BDL animals received NAC (0.25% and 1% w: v) in drinking water for 28 consecutive days. Finally, urine, blood, and kidney samples were collected and analyzed. Significant elevation in serum biomarkers of renal injury, along with urine markers of kidney damage, was evident in the BDL group. Moreover, markers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, protein carbonylation, and increased oxidized glutathione (GSSG) were evident detected in the kidney of cholestatic rats. Renal tissue antioxidant capacity and reduced glutathione (GSH) were also significantly depleted in the BDL group. Significant mitochondrial depolarization, depleted ATP content, and mitochondrial permeabilization was also detected in mitochondria isolated from the kidney of cholestatic animals. Renal histopathological alterations consisted of significant tissue fibrosis, interstitial inflammation, and tubular atrophy. It was found that NAC (0.25 and 1% in drinking water for 28 consecutive days) blunted histopathological changes, decreased markers of oxidative stress, and improved mitochondrial indices in the kidney of cirrhotic rats. Moreover, serum and urine biomarkers of renal injury were also mitigated in upon NAC treatment. These data indicate a potential renoprotective role for NAC in cholestasis. The effects of NAC on cellular redox state and mitochondrial function seem to play a fundamental role in its renoprotective effects during CN.},
}

@article {pmid32622850,
year = {2020},
author = {Iordache, AM and Buga, AM and Albulescu, D and Vasile, RC and Mitrut, R and Georgiadis, G and Zisis, IE and Mamoulakis, C and Tsatsakis, A and Docea, AO and Calina, D},
title = {Phosphodiesterase-5 inhibitors ameliorate structural kidney damage in a rat model of contrast-induced nephropathy.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {143},
number = {},
pages = {111535},
doi = {10.1016/j.fct.2020.111535},
pmid = {32622850},
issn = {1873-6351},
mesh = {Animals ; Contrast Media/*adverse effects ; Kidney Diseases/*chemically induced/prevention & control ; Kidney Tubules/*drug effects/pathology ; Male ; Phosphodiesterase 5 Inhibitors/*pharmacology ; Rats ; Rats, Wistar ; Sildenafil Citrate/*therapeutic use ; Tadalafil/*therapeutic use ; },
abstract = {The aim of the study was to investigate the potential of sildenafil and tadalafil to ameliorate structural kidney damage in contrast-induced nephropathy (CIN). A rat model of CIN was developed by dehydration, administration of a nitric oxide inhibitor and a prostaglandin synthesis inhibitor (L-NAME/indomethacin) and contrast media exposure to iopromide. The effect of pre-treatment with sildenafil, tadalafil or N-acetyl cysteine (NAC) for 7 days prior to CIN induction was investigated. All animals were sacrificed at 24 h after CIN induction and both kidneys were collected. Histopathological examination was performed under light microscopy in serial tissue sections stained with hematoxylin and eosin. CIN group showed hydropic changes of the renal tubules (proximal and distal convoluted tubules and Henle's loop), an increased Bowman space with lobulated glomerulus and alteration of macula densa region of distal convolute tubules. The groups pretreated with sildenafil and tadalafil showed nearly normal histological aspects of renal tissue. The group pretreated with NAC showed similar but less intense histopathologic changes compared to CIN group. Sildenafil and tadalafil pre-treatment ameliorates CIN-related structural kidney damage and the protective potential of these agents is superior to NAC.},
}

Animals
Contrast Media/*adverse effects
Kidney Diseases/*chemically induced/prevention & control
Kidney Tubules/*drug effects/pathology
Male
Phosphodiesterase 5 Inhibitors/*pharmacology
Rats
Rats, Wistar
Sildenafil Citrate/*therapeutic use
Tadalafil/*therapeutic use

@article {pmid32020997,
year = {2019},
author = {Chacko, B and Peter, JV},
title = {Antidotes in Poisoning.},
journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine},
volume = {23},
number = {Suppl 4},
pages = {S241-S249},
pmid = {32020997},
issn = {0972-5229},
abstract = {INTRODUCTION: Antidotes are agents that negate the effect of a poison or toxin. Antidotes mediate its effect either by preventing the absorption of the toxin, by binding and neutralizing the poison, antagonizing its end-organ effect, or by inhibition of conversion of the toxin to more toxic metabolites. Antidote administration may not only result in the reduction of free or active toxin level, but also in the mitigation of end-organ effects of the toxin by mechanisms that include competitive inhibition, receptor blockade or direct antagonism of the toxin.

Reduction in free toxin level can be achieved by specific and non-specific agents that bind to the toxin. The most commonly used non-specific binding agent is activated charcoal. Specific binders include chelating agents, bioscavenger therapy and immunotherapy. In some situations, enhanced elimination can be achieved by urinary alkalization or hemadsorption. Competitive inhibition of enzymes (e.g. ethanol for methanol poisoning), enhancement of enzyme function (e.g. oximes for organophosphorus poisoning) and competitive receptor blockade (e.g. naloxone, flumazenil) are other mechanisms by which antidotes act. Drugs such as N-acetyl cysteine and sodium thiocyanate reduce the formation of toxic metabolites in paracetamol and cyanide poisoning respectively. Drugs such as atropine and magnesium are used to counteract the end-organ effects in organophosphorus poisoning. Vitamins such as vitamin K, folic acid and pyridoxine are used to antagonise the effects of warfarin, methotrexate and INH respectively in the setting of toxicity or overdose. This review provides an overview of the role of antidotes in poisoning.

HOW TO CITE THIS ARTICLE: Chacko B, Peter JV. Antidotes in Poisoning. Indian J Crit Care Med 2019;23(Suppl 4):S241-S249.},
}

@article {pmid31531084,
year = {2019},
author = {Barzi, F and Miri, R and Sadeghi, R and Sistanizad, M and Sadeghi, M and Mahjoob, MP and Chehrazi, M},
title = {A Randomized Double Blind Placebo Controlled Trial Examining the Effects of Pentoxifylline on Contrast Induced Nephropathy Reduction after Percutaneous Coronary Intervention in High Risk Candidates.},
journal = {Iranian journal of pharmaceutical research : IJPR},
volume = {18},
number = {2},
pages = {1040-1046},
pmid = {31531084},
issn = {1735-0328},
abstract = {Contrast-induced nephropathy (CIN) (known as contrast-induced acute kidney injury) occurs as a result of acute worsening of renal function following a procedure with administration of iodine contrasts agent and remains a substantial concern in clinical practices. The purpose of this study is to investigate the preventive effect of Pentoxifylline supplementation on reduction of CIN occurrence after percutaneous coronary intervention among patients who were high risk of CIN according to Mehran score. In randomized, double-blind clinical trial patients who undergo coronary angiography with Mehran Score ≥ 11 consisted of our population. Patients in a ratio 1:1, divided into two groups received saline 0.9% plus N-acetyl cysteine and Pentoxifylline 400 mg three times per day 24 h before angiography until 48 h after angiography. In control group, the patients received placebo instead of PTX in a same manner as the control group. The endpoint was the incidence of CIN defined as creatinine increase of 0.5 mg/dL within 2 days after contrast. There were no significant differences in baseline characteristics. CIN occurred in 3 (5.5%) and 4 (7.3%) patients of the both groups (Pentoxifylline and control), respectively (p = 0.69; incidence odds ratio 1.36; 95% CI 0.29-6.38). No significant differences were seen in secondary outcome measures and changes in the level of creatinine (p = 0.54). In high-risk patients undergoing coronary angiography pentoxifylline supplementation had protection effect against contrast-induced nephropathy greater than placebo based hydration, but, not supported by our data.},
}

@article {pmid31212064,
year = {2019},
author = {García-Arroyo, FE and Gonzaga, G and Muñoz-Jiménez, I and Osorio-Alonso, H and Iroz, A and Vecchio, M and Tapia, E and Roncal-Jiménez, CA and Johnson, RJ and Sánchez-Lozada, LG},
title = {Antioxidant supplements as a novel mean for blocking recurrent heat stress-induced kidney damage following rehydration with fructose-containing beverages.},
journal = {Free radical biology & medicine},
volume = {141},
number = {},
pages = {182-191},
doi = {10.1016/j.freeradbiomed.2019.06.016},
pmid = {31212064},
issn = {1873-4596},
mesh = {Active Transport, Cell Nucleus ; Aldehyde Reductase/metabolism ; Animals ; Antioxidants/administration & dosage/*pharmacology ; *Beverages ; Blood Pressure ; Cell Nucleus/metabolism ; Dehydration ; Fluid Therapy ; Fructokinases/metabolism ; Fructose/*adverse effects ; Glutathione/metabolism ; *Heat-Shock Response ; Kidney Diseases/*metabolism ; Male ; Nitric Oxide Synthase Type III/metabolism ; Polymers/metabolism ; Protein Transport ; Rats ; Rats, Wistar ; },
abstract = {Recently repeated heat stress and dehydration have been reported to cause oxidative stress and kidney damage that is enhanced by rehydrating with fructose solutions. We hypothesized that antioxidants might provide a novel way to prevent kidney damage. To test this hypothesis, mild heat stress was induced by exposing rats to 37 °C during 1 h in a closed chamber. The supplementation with water-soluble antioxidants (Antiox), ascorbic acid 1% plus N-acetyl cysteine 600 mg/L was done either in the 10% fructose 2 h rehydration fluid immediately after heat stress (Fructose 10% + Antiox), and/or in the tap water (Water + Antiox) for the remainder of the day, or in both fluids. After 4 weeks, control rats exposed to heat with fructose rehydration developed impaired renal function, tubular injury, intrarenal oxidative stress, a reduction in Nrf2-Keap1 antioxidant pathway, stimulation of vasopressin and the intrarenal polyol-fructokinase pathway. In contrast, dosing the antioxidants in the tap water (i.e., before the heat exposure and rehydration with fructose) preserved renal function, prevented renal tubule dysfunction and avoided the increase in systemic blood pressure. These effects were likely due to the amplification of the antioxidant defenses through increased Nrf2 nuclear translocation stimulated by the antioxidants and by the prevention of polyol fructokinase pathway overactivation. More studies to understand the mechanisms implicated in this pathology are warranted as there is recent evidence that they may be operating in humans as well.},
}

Active Transport, Cell Nucleus
Aldehyde Reductase/metabolism
Animals
Antioxidants/administration & dosage/*pharmacology
*Beverages
Blood Pressure
Cell Nucleus/metabolism
Dehydration
Fluid Therapy
Fructokinases/metabolism
Fructose/*adverse effects
Glutathione/metabolism
*Heat-Shock Response
Kidney Diseases/*metabolism
Male
Nitric Oxide Synthase Type III/metabolism
Polymers/metabolism
Protein Transport
Rats
Rats, Wistar

@article {pmid30829731,
year = {2019},
author = {Bellos, I and Iliopoulos, DC and Perrea, DN},
title = {Allopurinol Administration for the Prevention of Contrast-Induced Nephropathy: A Network Meta-analysis With Trial Sequential Analysis.},
journal = {Journal of cardiovascular pharmacology},
volume = {73},
number = {5},
pages = {307-315},
doi = {10.1097/FJC.0000000000000663},
pmid = {30829731},
issn = {1533-4023},
mesh = {Acute Kidney Injury/chemically induced/epidemiology/physiopathology/*prevention & control ; Allopurinol/adverse effects/*therapeutic use ; Contrast Media/*adverse effects ; Cytoprotection ; Fluid Therapy ; Gout Suppressants/adverse effects/*therapeutic use ; Humans ; Incidence ; Kidney/*drug effects/physiopathology ; Randomized Controlled Trials as Topic ; Risk Factors ; Treatment Outcome ; },
abstract = {Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although the optimal one remains still unknown. The aim of the present meta-analysis is to accumulate current literature knowledge and evaluate the renoprotective effects of allopurinol administration before contrast medium exposure. To achieve this, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to November 8, 2018. Statistical meta-analysis was conducted with Review Manager 5.3, TSA 0.9.5.5 and R-3.4.3. Six studies were included with a total of 918 patients. Quantitative synthesis revealed that allopurinol leads to significantly reduced incidence of contrast-induced nephropathy compared with hydration alone [odds ratio: 0.29, 95% confidence interval: (0.09-0.90)]. Trial sequential analysis suggested that Z-curve crossed the O'Brien-Fleming significance boundaries, although required information size was not reached. Network meta-analysis indicated that allopurinol had the highest probability (81.2%) to rank as the most effective intervention compared with hydration and N-acetyl cysteine; however, significant overlap with the rest treatments was noted. In conclusion, the present meta-analysis suggests that allopurinol may represent a promising measure for the prevention of acute kidney injury after coronary angiography. Future large-scale randomized controlled trials should verify this finding, while combinations of allopurinol with other novel interventions should be evaluated to define the most effective strategy to be implemented in the clinical setting.},
}

Acute Kidney Injury/chemically induced/epidemiology/physiopathology/*prevention & control
Allopurinol/adverse effects/*therapeutic use
Contrast Media/*adverse effects
Cytoprotection
Fluid Therapy
Gout Suppressants/adverse effects/*therapeutic use
Humans
Incidence
Kidney/*drug effects/physiopathology
Randomized Controlled Trials as Topic
Risk Factors
Treatment Outcome

@article {pmid30021379,
year = {2018},
author = {Yan, J and Li, M and Wang, XD and Lu, ZY and Ni, XL},
title = {Peperomin E (PepE) protects against high fat diet-induced atherosclerosis in Apolipoprotein E deficient (ApoE[-/-]) mice through reducing inflammation via the suppression of NLRP3 signaling pathway.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {105},
number = {},
pages = {862-869},
doi = {10.1016/j.biopha.2018.04.140},
pmid = {30021379},
issn = {1950-6007},
mesh = {Animals ; Apolipoproteins E/*deficiency ; Atherosclerosis/metabolism/*prevention & control ; Benzodioxoles/pharmacology/*therapeutic use ; Cell Survival/drug effects/physiology ; Diet, High-Fat/*adverse effects ; Inflammation/drug therapy/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & inhibitors/metabolism ; Reactive Oxygen Species/antagonists & inhibitors/metabolism ; Signal Transduction/*drug effects/physiology ; },
abstract = {Peperomin E (PepE) is a type of secolignan, a major component of the plant Peperomia dindygulensis. It has been shown to exert anti-inflammatory effects; however, the effects of PepE on human atherosclerosis remain unexplored. In the study, we investigated the role of PepE in high fat diet (HFD) induced atherosclerosis using apolipoprotein E defcient (ApoE[-/-]) mice. Elevated serum homocyteine, cholesterol, and triglyceride levels, accelerated progression of atherosclerosis and exacerbated macrophage infiltration into atherosclerotic lesions were observed in HFD-fed ApoE[-/-] mice, which were attenuated by PepE treatment. ApoE[-/-] mice fed with HFD exhibited significantly high levels of inflammation-associated regulators in artery tissues, accompanied with an increased expression of p-inhibitor of κBα (IκBα) and p-nuclear factor-kappa B (NF-κB), and the process was blocked by PepE administration. Further, we found NOD-like receptor pyrin 3 (NLRP3) inflammasome activation in artery tissues of HFD-fed ApoE[-/-] mice. In vitro, silencing NLRP3 using small interfering RNA efficiently inhibited oxidized-low-density lipoprotein (oxLDL)-induced ASC and Caspase-1 expressions, interleukin (IL)-1β and IL-18 production in human aortic endothelial cells (HAECs). Further experiments indicated that NLRP3-ASC pathway was activated by reactive oxygen species (ROS), since ROS scavenger of N-acetyl-cysteine (NAC) prevented, which was further reduced by PepE addition. However, the anti-inflammatory effects of PepE on oxLDL-incubated HAECs were abolished by over-expression NLRP3. Together, our study revealed that PepE inhibited atherosclerosis development in HFD-fed ApoE[-/-] mice by suppressing NLRP3 inflammatory signaling pathway, and suggested that PepE might be a potential therapeutic strategy in the prevention of atherosclerosis.},
}

Animals
Apolipoproteins E/*deficiency
Atherosclerosis/metabolism/*prevention & control
Benzodioxoles/pharmacology/*therapeutic use
Cell Survival/drug effects/physiology
Diet, High-Fat/*adverse effects
Inflammation/drug therapy/metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & inhibitors/metabolism
Reactive Oxygen Species/antagonists & inhibitors/metabolism
Signal Transduction/*drug effects/physiology

@article {pmid28410397,
year = {2017},
author = {Visagie, MH and van den Bout, I and Joubert, AM},
title = {A bis-sulphamoylated estradiol derivative induces ROS-dependent cell cycle abnormalities and subsequent apoptosis.},
journal = {PloS one},
volume = {12},
number = {4},
pages = {e0176006},
pmid = {28410397},
issn = {1932-6203},
mesh = {2-Methoxyestradiol ; Acetylcysteine/pharmacology ; Apoptosis/*drug effects ; Autophagy/drug effects ; Cell Line, Tumor ; DNA Breaks, Double-Stranded/drug effects ; Estradiol/*analogs & derivatives/*toxicity ; G2 Phase Cell Cycle Checkpoints/drug effects ; Histones/metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; M Phase Cell Cycle Checkpoints/drug effects ; MCF-7 Cells ; Membrane Potential, Mitochondrial/drug effects ; Oxidative Stress/drug effects ; Phosphorylation/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {Clinical trials have revealed that the potential anticancer agent, 2-methoxyestradiol (2ME2) has limitations due to its low bioavailability. Subsequently, 2ME2 derivatives including (8R,13S,14S,17S)-2-ethyl-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrane-3,17-diyl bis(sulphamate) (EMBS) have shown improved efficacies in inducing apoptosis. However, no conclusive data exist to explain the mode of action exerted by these drugs. This study investigated the mode of action used by EMBS as a representative of the sulphamoylated 2ME2 derivatives. Hydrogen peroxide and superoxide production was quantified using dichlorofluorescein diacetate and hydroethidine. Cell proliferation and mitochondrial metabolism were investigated using crystal violet and Alamar Blue. Apoptosis was assessed using Annexin V-FITC while mitochondrial integrity was assessed using Mitocapture. Autophagy was visualised using LC3B II antibodies. The effects of EMBS on H2A phosphorylation and nuclei were visualised using phospho H2A antibody and 4',6-diamidino-2-phenylindole, dihydrochloride. Data showed that EMBS exposure leads to increased reactive oxygen species (ROS) production which is correlated with loss of cell proliferation, mitochondrial membrane damage, decreased metabolic activity, G2/M arrest, endoreduplication, DNA double stranded breaks, micronuclei and apoptosis induction. Treatment of EMBS-exposed cells with the ROS scavenger, N-acetyl cysteine, abrogated ROS production, cell cycle arrest and apoptosis implying an essential role for ROS production in EMBS signaling. The inhibition of c-Jun N-terminal kinase (JNK) activity also inhibited EMBS-induced apoptosis suggesting that EMBS triggers apoptosis via the JNK pathway. Lastly, evaluation of LC3IIB protein levels indicated that autophagy is not activated in EMBS-exposed cells. Our data shows that EMBS targets a pathway that leads to increased ROS production as an early event that culminates in G2/M arrest and apoptosis by means of JNK-signaling in cancer cells. This study suggests a novel oxidative stress-dependent mode of action for sulphamoylated derivatives.},
}

2-Methoxyestradiol
Acetylcysteine/pharmacology
Apoptosis/*drug effects
Autophagy/drug effects
Cell Line, Tumor
DNA Breaks, Double-Stranded/drug effects
Estradiol/*analogs & derivatives/*toxicity
G2 Phase Cell Cycle Checkpoints/drug effects
Histones/metabolism
Humans
JNK Mitogen-Activated Protein Kinases/metabolism
M Phase Cell Cycle Checkpoints/drug effects
MCF-7 Cells
Membrane Potential, Mitochondrial/drug effects
Oxidative Stress/drug effects
Phosphorylation/drug effects
Reactive Oxygen Species/metabolism

@article {pmid25715308,
year = {2015},
author = {Nadkarni, GN and Konstantinidis, I and Patel, A and Yacoub, R and Kumbala, D and Patel, RA and Annapureddy, N and Pakanati, KC and Simoes, PK and Javed, F and Benjo, AM},
title = {Trimetazidine Decreases Risk of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.},
journal = {Journal of cardiovascular pharmacology and therapeutics},
volume = {20},
number = {6},
pages = {539-546},
doi = {10.1177/1074248415573320},
pmid = {25715308},
issn = {1940-4034},
mesh = {Aged ; Contrast Media/*adverse effects ; Female ; Humans ; Kidney Diseases/*chemically induced/*prevention & control ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Renal Insufficiency, Chronic/*complications ; Trimetazidine/*therapeutic use ; Vasodilator Agents/*therapeutic use ; },
abstract = {OBJECTIVES: We sought to synthesize and analyze the available data from randomized controlled trials (RCTs) for trimetazidine (TMZ) in the prevention of contrast-induced nephropathy (CIN).

BACKGROUND: Contrast-induced nephropathy after coronary angiography is associated with poor outcomes. Trimetazidine is an anti-ischemic drug that might reduce incidence of CIN, but current data are inconclusive.

METHODS: We searched MEDLINE/PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and ScienceDirect electronic databases for RCTs comparing intravenous hydration with normal saline (NS) and/or N-acetyl cysteine (NAC) versus TMZ plus NS ± NAC for prevention of CIN. We used RevMan 5.2 for statistical analysis with the fixed effects model.

RESULTS: Of the 808 studies, 3 RCTs met criteria with 290 patients in the TMZ plus NS ± NAC group and 292 patients in the NS ± NAC group. The mean age of patients was 59.5 years, and baseline serum creatinine ranged from 1.3 to 2 mg/dL. Trimetazidine significantly reduced the incidence of CIN by 11% (risk difference 0.11; 95% confidence interval, 0.16-0.06; P < .01). There was no significant heterogeneity between the studies (I(2) statistic = 0). The number needed to treat to prevent 1 episode of CIN was 9.

CONCLUSIONS: The addition of TMZ to NS ± NAC significantly decreased the incidence of CIN in patients undergoing coronary angiography. In conclusion, TMZ could be considered as a potential tool for prevention of CIN in patients with renal dysfunction.},
}

Aged
Contrast Media/*adverse effects
Female
Humans
Kidney Diseases/*chemically induced/*prevention & control
Male
Middle Aged
Randomized Controlled Trials as Topic
Renal Insufficiency, Chronic/*complications
Trimetazidine/*therapeutic use
Vasodilator Agents/*therapeutic use

@article {pmid25352760,
year = {2014},
author = {Yoo, HJ and Im, CN and Youn, DY and Yun, HH and Lee, JH},
title = {Bis is Induced by Oxidative Stress via Activation of HSF1.},
journal = {The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology},
volume = {18},
number = {5},
pages = {403-409},
pmid = {25352760},
issn = {1226-4512},
abstract = {The Bis protein is known to be involved in a variety of cellular processes including apoptosis, migration, autophagy as well as protein quality control. Bis expression is induced in response to a number of types of stress, such as heat shock or a proteasome inhibitor via the activation of heat shock factor (HSF)1. We report herein that Bis expression is increased at the transcriptional level in HK-2 kidney tubular cells and A172 glioma cells by exposure to oxidative stress such as H2O2 treatment and oxygen-glucose deprivation, respectively. The pretreatment of HK-2 cells with N-acetyl cysteine, suppressed Bis induction. Furthermore, HSF1 silencing attenuated Bis expression that was induced by H2O2, accompaniedby increase in reactive oxygen species (ROS) accumulation. Using a series of deletion constructs of the bis gene promoter, two putative heat shock elements located in the proximal region of the bis gene promoter were found to be essential for the constitutive expression is as well as the inducible expression of Bis. Taken together, our results indicate that oxidative stress induces Bis expression at the transcriptional levels via activation of HSF1, which might confer an expansion of antioxidant capacity against pro-oxidant milieu. However, the possible role of the other cis-element in the induction of Bis remains to be determined.},
}

@article {pmid24932583,
year = {2014},
author = {Thakur, P and Lamoke, F and Chaffin, JM and Bartoli, M and Lee, JR and Duncan, MB},
title = {Dysplastic hepatocytes develop nuclear inclusions in a mouse model of viral hepatitis.},
journal = {PloS one},
volume = {9},
number = {6},
pages = {e99872},
pmid = {24932583},
issn = {1932-6203},
mesh = {Aldehydes/metabolism ; Animals ; Biomarkers/metabolism ; Cell Death ; Cell Nucleus/metabolism ; Cell Nucleus Size ; Cellular Senescence ; Disease Models, Animal ; Endoplasmic Reticulum/metabolism ; Glycogen/metabolism ; Hepatitis/immunology/*pathology/*virology ; Hepatitis B Surface Antigens/immunology ; Hepatocytes/metabolism/*pathology/*virology ; Intranuclear Inclusion Bodies/*pathology ; Mice, Inbred C57BL ; Mice, Transgenic ; Oxidative Stress ; Proliferating Cell Nuclear Antigen/metabolism ; Vacuoles/metabolism ; },
abstract = {Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER) stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis.},
}

Aldehydes/metabolism
Animals
Biomarkers/metabolism
Cell Death
Cell Nucleus/metabolism
Cell Nucleus Size
Cellular Senescence
Disease Models, Animal
Endoplasmic Reticulum/metabolism
Glycogen/metabolism
Hepatitis/immunology/*pathology/*virology
Hepatitis B Surface Antigens/immunology
Hepatocytes/metabolism/*pathology/*virology
Intranuclear Inclusion Bodies/*pathology
Mice, Inbred C57BL
Mice, Transgenic
Oxidative Stress
Proliferating Cell Nuclear Antigen/metabolism
Vacuoles/metabolism

@article {pmid23723505,
year = {2013},
author = {Vikramkumar, AG and Kuruvila, S and Ganguly, S},
title = {Monilethrix: a rare hereditary condition.},
journal = {Indian journal of dermatology},
volume = {58},
number = {3},
pages = {243},
pmid = {23723505},
issn = {1998-3611},
abstract = {Monilethrix is a rare hereditary condition generally considered to be an autosomal-dominant disorder with variable penetrance. Here, we report a case of monilethrix in a 13-year-old boy with an affected sibling. A therapeutic trial with oral N-acetyl cysteine was attempted. There was slight improvement after 2 months of therapy. The hair density, however, did not show any further improvement subsequently. Monilethrix remains as a therapeutic challenge for dermatologists.},
}

@article {pmid19955665,
year = {2009},
author = {Thomson, VS and Narayanan, K and Singh, JC},
title = {Contrast induced nephropathy in urology.},
journal = {Indian journal of urology : IJU : journal of the Urological Society of India},
volume = {25},
number = {4},
pages = {437-445},
pmid = {19955665},
issn = {1998-3824},
abstract = {Intravenous contrast agents have a distinct role in urological imaging: to study precise anatomical delineation, vascularity, and to assess the function of the renal unit. Contrast induced nephropathy (CIN) is a known adverse effect of intravenous contrast administration. The literature on incidence, pathophysiology, clinical features, and current preventive strategies available for CIN relevant to urologists was reviewed. A search of the PubMed database was done using the keywords nephropathy and media, prevention and control or prevention Contrast media (explode), all adverse effects, and kidney diseases (explode). An online search of the EMBASE database for the time ranging from 1977 to February 2009 was performed using the keywords ionic contrast medium, adverse drug reaction, major or controlled clinical study, human, nephrotoxicity, and kidney disease. Current publications and data most relevant to urologists were examined. CIN was the third most common cause of hospital-acquired renal failure. The incidence is less common with intravenous contrast administration as compared with intra-arterial administration. The pathogenesis of contrast mediated nephropathy is due to a combination of toxic injury to renal tubules and medullary ischemic injury mediated by reactive oxygen species. CIN most commonly manifests as a nonoliguric and asymptomatic transient decline in renal function. Patients who developed CIN were found to have increased mortality, longer hospital stay, and complicated clinical course. An overview of risk factors and risk prediction score for prognostication of CIN are elaborated. Preventive strategies including choice of contrast agents, maximum tolerated dose, role of hydration, hydration regime, etc. are discussed. The role of N- acetyl cysteine, Theophylline, Fenoldapam, Endothelin receptor antagonists, iloprost, atrial natriuretic peptide, and newer therapies such as targeted renal therapy (TRT) are discussed. A working algorithm based on current evidence is proposed. No current treatment can reverse or ameliorate CIN once it occurs, but prophylaxis is possible.},
}

@article {pmid16614485,
year = {2006},
author = {Mizuguchi, S and Takemura, S and Minamiyama, Y and Kodai, S and Tsukioka, T and Inoue, K and Okada, S and Suehiro, S},
title = {S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats.},
journal = {BioFactors (Oxford, England)},
volume = {26},
number = {1},
pages = {81-92},
doi = {10.1002/biof.5520260108},
pmid = {16614485},
issn = {0951-6433},
mesh = {Animals ; Bronchoalveolar Lavage Fluid/cytology ; Carbon Tetrachloride/*pharmacology ; Cysteine/*analogs & derivatives/pharmacology ; Enzyme Precursors/analysis ; Glutathione/analysis ; Hydroxyproline/analysis ; Liver/pathology ; Lung/chemistry ; Male ; Matrix Metalloproteinase 9/analysis ; Nitric Oxide/urine ; Nitric Oxide Synthase Type II/analysis ; Oxidative Stress/*drug effects ; Pulmonary Fibrosis/*chemically induced/*prevention & control ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Sulfhydryl Compounds/blood ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; },
abstract = {This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.},
}

Animals
Bronchoalveolar Lavage Fluid/cytology
Carbon Tetrachloride/*pharmacology
Cysteine/*analogs & derivatives/pharmacology
Enzyme Precursors/analysis
Glutathione/analysis
Hydroxyproline/analysis
Liver/pathology
Lung/chemistry
Male
Matrix Metalloproteinase 9/analysis
Nitric Oxide/urine
Nitric Oxide Synthase Type II/analysis
Oxidative Stress/*drug effects
Pulmonary Fibrosis/*chemically induced/*prevention & control
Rats
Rats, Wistar
Reactive Oxygen Species/metabolism
Sulfhydryl Compounds/blood
Transforming Growth Factor beta
Transforming Growth Factor beta1

@article {pmid16551579,
year = {2006},
author = {Floriano-Sánchez, E and Villanueva, C and Medina-Campos, ON and Rocha, D and Sánchez-González, DJ and Cárdenas-Rodríguez, N and Pedraza-Chaverrí, J},
title = {Nordihydroguaiaretic acid is a potent in vitro scavenger of peroxynitrite, singlet oxygen, hydroxyl radical, superoxide anion and hypochlorous acid and prevents in vivo ozone-induced tyrosine nitration in lungs.},
journal = {Free radical research},
volume = {40},
number = {5},
pages = {523-533},
doi = {10.1080/10715760500419365},
pmid = {16551579},
issn = {1071-5762},
mesh = {Animals ; Antioxidants/chemistry/pharmacology ; Dose-Response Relationship, Drug ; Free Radical Scavengers/chemistry/*pharmacology ; Hydroxyl Radical/metabolism ; Hypochlorous Acid/metabolism ; Immunohistochemistry ; Lung/*drug effects/metabolism ; Male ; Masoprocol/chemistry/*pharmacology ; Ozone/*pharmacology ; Peroxynitrous Acid/metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species/*metabolism ; Singlet Oxygen/metabolism ; Superoxides/metabolism ; Tyrosine/metabolism ; },
abstract = {The antioxidant nordihydroguaiaretic acid (NDGA) has recently become well known as a putative anticancer drug. In this paper, it was evaluated the in vitro peroxynitrite (ONOO(-)), singlet oxygen ((1)O(2)), hydroxyl radical (OH(v)), hydrogen peroxide (H(2)O(2)), superoxide anion and hypochlorous acid (HOCl) scavenging capacity of NDGA. It was found that NDGA scavenges: (a) ONOO(-) (IC(50) = 4 +/- 0.94 microM) as efficiently as uric acid; (b) (1)O(2) (IC(50) = 151 +/- 20 microM) more efficiently than dimethyl thiourea, lipoic acid, N-acetyl-cysteine and glutathione; (c) OH(v) (IC(50) = 0.15 +/- 0.02 microM) more efficiently than dimethyl thiourea, uric acid, trolox, dimethyl sulfoxide and mannitol, (d) (IC(50) = 15 +/- 1 microM) more efficiently than N-acetyl-cysteine, glutathione, tempol and deferoxamine and (e) HOCl (IC(50) = 622 +/- 42 microM) as efficiently as lipoic acid and N-acetyl-cysteine. NDGA was unable to scavenge H(2)O(2). In an in vivo study in rats, NDGA was able to prevent ozone-induced tyrosine nitration in lungs. It is concluded that NDGA is a potent in vitro scavenger of ONOO(-), (1)O(2), OH(v), and HOCl and is able to prevent lung tyrosine nitration in vivo.},
}

Animals
Antioxidants/chemistry/pharmacology
Dose-Response Relationship, Drug
Free Radical Scavengers/chemistry/*pharmacology
Hydroxyl Radical/metabolism
Hypochlorous Acid/metabolism
Immunohistochemistry
Lung/*drug effects/metabolism
Male
Masoprocol/chemistry/*pharmacology
Ozone/*pharmacology
Peroxynitrous Acid/metabolism
Rats
Rats, Wistar
Reactive Oxygen Species/*metabolism
Singlet Oxygen/metabolism
Superoxides/metabolism
Tyrosine/metabolism

@article {pmid11562447,
year = {2001},
author = {Guermonprez, L and Ducrocq, C and Gaudry-Talarmain, YM},
title = {Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants.},
journal = {Molecular pharmacology},
volume = {60},
number = {4},
pages = {838-846},
pmid = {11562447},
issn = {0026-895X},
mesh = {Acetates/metabolism ; Acetylcholine/*antagonists & inhibitors/biosynthesis ; Animals ; Antioxidants/*pharmacology ; Biological Transport/drug effects ; Carbon Radioisotopes ; Choline/metabolism ; Choline O-Acetyltransferase/antagonists & inhibitors/*metabolism ; Drug Interactions ; Molsidomine/analogs & derivatives/pharmacology ; Nitrates/*pharmacology ; Oxidants/*pharmacology ; Reducing Agents/pharmacology ; Torpedo ; Tyrosine/*analogs & derivatives/*metabolism ; Uric Acid/pharmacology ; },
abstract = {Evidence of an overload of reactive oxygen species and peroxynitrite, a derivative of nitric oxide, in sporadic amyotrophic lateral sclerosis suggests that peroxynitrite could impair cholinergic functions. Because of the impossibility of obtaining synaptosomes from vertebrate neuromuscular junctions, we used cholinergic synaptosomes purified from Torpedo marmorata electroneurons to characterize the defects triggered by peroxynitrite in more detail. Addition of peroxynitrite or its donor 3-morpholinosydnonimine abolished high-affinity choline uptake and synthesis of acetylcholine from acetate. T. marmorata choline acetyltransferase (ChAT) was impaired to the same extent as bovine brain ChAT. A hallmark of peroxynitrite action is the nitration of tyrosine residues in proteins. Peroxynitrite induced a concentration-dependent appearance of nitrotyrosines in several neuronal proteins from synaptosomes and, more readily, from synaptic vesicles. Peroxynitrite also triggered tyrosine nitrations in purified ChAT. Peroxynitrite-dependent nitrations were impaired when synaptosomes were pretreated with thioreductants (glutathione, N-acetyl cysteine, dithiothreitol) or antioxidants (uric acid, melatonin, bovine serum albumin, desferrioxamine). Deleterious effects of peroxynitrite on choline transport and ChAT activity were prevented by the thioreductants but only partially by the antioxidants, suggesting a mechanism other than tyrosine nitration, which may involve cysteine oxidation. Further development of protective agents acting on choline transport and on ChAT activity may offer interesting therapeutic possibilities with respect to cholinergic dysfunction occurring in neurodegenerative diseases.},
}

Acetates/metabolism
Acetylcholine/*antagonists & inhibitors/biosynthesis
Animals
Antioxidants/*pharmacology
Biological Transport/drug effects
Carbon Radioisotopes
Choline/metabolism
Choline O-Acetyltransferase/antagonists & inhibitors/*metabolism
Drug Interactions
Molsidomine/analogs & derivatives/pharmacology
Nitrates/*pharmacology
Oxidants/*pharmacology
Reducing Agents/pharmacology
Torpedo
Tyrosine/*analogs & derivatives/*metabolism
Uric Acid/pharmacology

@article {pmid11500943,
year = {2001},
author = {Núñez, MT and Osorio, A and Tapia, V and Vergara, A and Mura, CV},
title = {Iron-induced oxidative stress up-regulates calreticulin levels in intestinal epithelial (Caco-2) cells.},
journal = {Journal of cellular biochemistry},
volume = {82},
number = {4},
pages = {660-665},
doi = {10.1002/jcb.1194},
pmid = {11500943},
issn = {0730-2312},
mesh = {Acetylcysteine/pharmacology ; Antioxidants/pharmacology ; Caco-2 Cells ; Calcium-Binding Proteins/*biosynthesis/genetics ; Calreticulin ; Humans ; Intestinal Mucosa/*metabolism ; Iron/*pharmacology ; *Oxidative Stress ; Quercetin/pharmacology ; RNA, Messenger/biosynthesis ; Ribonucleoproteins/*biosynthesis/genetics ; Thiourea/analogs & derivatives/pharmacology ; Up-Regulation ; },
abstract = {Calreticulin, a molecular chaperone involved in the folding of endoplasmic reticulum synthesized proteins, is also a shock protein induced by heat, food deprivation, and chemical stress. Mobilferrin, a cytosolic isoform of calreticulin, has been proposed to be an iron carrier for iron recently incoming into intestinal cells. To test the hypothesis that iron could affect calreticulin expression, we investigated the possible associations of calreticulin with iron metabolism. To that end, using Caco-2 cells as a model of intestinal epithelium, the mass and mRNA levels of calreticulin were evaluated as a function of the iron concentration in the culture media. Increasing the iron content in the culture from 1 to 20 microM produced an increase in calreticulin mRNA and a two-fold increase in calreticulin. Increasing iron also induced oxidative damage to proteins, as assessed by the formation of 4-hydroxy-2-nonenal adducts. Co-culture of cells with the antioxidants quercetin, dimethyltiourea and N-acetyl cysteine abolished both the iron-induced oxidative damage and the iron-induced increase in calreticulin. We postulate that the iron-induced expression of calreticulin is part of the cellular response to oxidative stress generated by iron.},
}

Acetylcysteine/pharmacology
Antioxidants/pharmacology
Caco-2 Cells
Calcium-Binding Proteins/*biosynthesis/genetics
Calreticulin
Humans
Intestinal Mucosa/*metabolism
Iron/*pharmacology
*Oxidative Stress
Quercetin/pharmacology
RNA, Messenger/biosynthesis
Ribonucleoproteins/*biosynthesis/genetics
Thiourea/analogs & derivatives/pharmacology
Up-Regulation