Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Protective Potential of Vinpocetine on Acrylamide Induced Liver Toxicity in Male Albino Rats","authors":"Eman M.S. Shaheen,&nbsp;Marwa A. E. Abd El-Maksoud","doi":"10.1002/jbt.71039","DOIUrl":"10.1002/jbt.71039","url":null,"abstract":"<p>Acrylamide is a highly reactive carbonyl compound extensively utilized in industrial applications. It shows a significant association with oxidative stress, neurotoxic, and genotoxic effects. This study sought to assess the protective effects of vinpocetine, a synthetic analog of the natural alkaloid vincamine, which exhibits strong antioxidant and anti-inflammatory properties, against ACR-induced hepatic injury. Experimental animals were categorized into four groups and orally treated as follows: control group, Vinpo. group (5 mg/kg bw), Acrylamide group (38.27 mg/kg bw), and Vinpo. plus acrylamide group. Following the experimental period, biochemical analyses revealed that ACR administration significantly elevated hepatic marker enzymes and lipid profile as well as increased oxidative stress markers such as malondialdehyde (MDA) and tumor necrosis factor (TNF-α) immunoexpression levels, with concomitant reductions in antioxidant defenses (catalase “CAT” and superoxide dismutase “SOD”). Conversely, co-administration of vinpocetine mitigated the ACR-induced alterations and helped in the normalization of biochemical parameters, enhancing antioxidant capacity and attenuation of histopathological damage and apoptotic processes.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morroniside Attenuates Doxorubicin-Induced Cardiotoxicity by Activating the PI3K/AKT/Nrf2/HO-1 Pathway to Inhibit Ferroptosis and Oxidative Stress","authors":"Zhi-Hui Lin,&nbsp;Xing-Yu Lin,&nbsp;Wen-Jie Lu,&nbsp;Meng-Qi Wu,&nbsp;Dong-Yan Song,&nbsp;Rui-Dong Cheng","doi":"10.1002/jbt.71016","DOIUrl":"10.1002/jbt.71016","url":null,"abstract":"<p>Cardiotoxicity induced by doxorubicin (Dox) significantly contributes to increased mortality among cancer patients, yet available pharmacological interventions remain scarce. Recent studies suggest that ferroptosis is a key mechanism in the development of Dox-induced cardiotoxicity (DIC). Morroniside (Mor), an active iridoid glycoside isolated from <i>Cornus officinalis</i>, exhibits multiple pharmacological properties such as antioxidant, anti-ferroptotic, and anti-inflammatory activities. Given this multi-target profile, Mor shows potential as a treatment option for reducing DIC. This work was designed to examine the association between Mor and DIC. In vivo DIC model, C57BL/J mice received 5 mg/kg/d Mor via oral gavage for 5 weeks. In vitro DIC model, H9c2 cells were exposed to 10 μM Mor over a 48-h period. Cardiac injury markers were quantified in serum and cell culture supernatants. Biochemical assays, western blotting, cellular immunofluorescence, and DHE/ROS staining were employed to evaluate ferroptosis and oxidative stress. Mor administration substantially reduced the levels of cardiac injury biomarkers while simultaneously attenuating ferroptosis and oxidative stress in vivo. In cellular models, Mor exhibited potent anti-ferroptotic and antioxidant effects through Nrf2 pathway activation. Further mechanistic studies identified PI3K/AKT pathway as the upstream regulator of Nrf2 activation in response to Mor treatment. Our study provided the first evidence for Mor's cardioprotective effects against DIC. Mechanistically, Mor attenuated DIC by suppressing ferroptosis and reducing oxidative stress via activation of the PI3K/AKT/Nrf2/HO-1 signaling pathway.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Elemene Triggers Drp1-Dependent Mitochondrial Fission Through CDK1/Cyclin B1 Signaling in Cervical Cancer Cells","authors":"Zhifang Li,&nbsp;Ling Tang,&nbsp;Mingyan Wang,&nbsp;Qiong Yu,&nbsp;Chen Chen,&nbsp;Jiyi Xia,&nbsp;Xiaolan Yu","doi":"10.1002/jbt.71032","DOIUrl":"10.1002/jbt.71032","url":null,"abstract":"<p>Mitochondrial dynamics, regulated by fission and fusion, are frequently altered in cancers, influencing cell survival and metabolism. The sesquiterpene β-elemene exhibits anti-tumor activity, but its effect on mitochondrial dynamics in cervical cancer is unknown. This study investigated whether β-elemene exerts its anti-tumor effects by disrupting mitochondrial homeostasis. We found that β-elemene treatment dose-dependently reduced viability and increased lactate dehydrogenase release in HT-3 and Caski cervical cancer cells. In HT-3 cells, β-elemene induced mitochondrial oxidative stress, impaired respiratory function, and triggered extensive mitochondrial fragmentation. Mechanistically, β-elemene promoted phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its translocation to mitochondria. Furthermore, β-elemene enhanced the interaction between cyclin-dependent kinase 1 (CDK1) and cyclin B1. Genetic silencing of CDK1 abrogated β-elemene-induced Drp1 activation, mitochondrial fragmentation, and bioenergetic deficits. Collectively, these data identify a novel pathway through which β-elemene drives CDK1-dependent Drp1 activation, leading to excessive mitochondrial fission and dysfunction in cervical cancer cells.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signaling Pathway in Age-Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy","authors":"Fu XinYu,&nbsp;Luo Yi,&nbsp;Zhang Liu","doi":"10.1002/jbt.70968","DOIUrl":"10.1002/jbt.70968","url":null,"abstract":"<div>\u0000 \u0000 <p>Age-related eye diseases (AREDs), such as diabetic retinopathy (DR), cataract, glaucoma, age-related macular degeneration (AMD), presbyopia, and represent the primary sources of vision impairment globally. Numerous investigations have indicated that the onset and progression of these conditions are significantly linked to oxidative stress (OS) affecting the eye. The Keap1-Nrf2-ARE signaling pathway is a well-established mechanism that defends the body against OS and inflammation. This pathway is also implicated in the advancement of AREDs. However, the contribution of Nrf2 is likely to be disease-context dependent, and in multifactorial conditions such as glaucoma and dry eye disease, OS should be viewed as one interacting mechanism among several pathogenic processes rather than the sole or dominant driver. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) serves as a key modulator of numerous life processes, playing a critical role in antioxidant mechanisms, anti-inflammatory activities, antifibrotic responses, and cancer development. This review emphasizes the possible role of Nrf2 in the onset and progression of AREDs. Additionally, it explores various Nrf2 activators, encompassing noncoding RNAs and external substances, that regulate Nrf2 expression via distinct pathways within ocular disease models and eye cells, thereby safeguarding them from harmful alterations. However, most evidence supporting Nrf2-targeted interventions in age-related eye diseases remains preclinical, and important issues including disease-specific ocular delivery, target engagement in human tissues, long-term safety, and the potential risks of chronic Nrf2 activation must be addressed before clinical translation can be considered feasible. Consequently, Nrf2 may represent a significant target for the safeguarding of ocular cells against assorted stressors and the prevention of ocular ailments.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP7A Orchestrates Tumor Progression and Cuproptosis in Hepatocellular Carcinoma via the LINC02038-miR-506-3p Regulatory Circuit","authors":"Zhe Liu,&nbsp;Weixi Shan,&nbsp;Wenyu Zhou,&nbsp;Meiying Long,&nbsp;Long Yang","doi":"10.1002/jbt.71027","DOIUrl":"10.1002/jbt.71027","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options, underscoring the urgent need for novel therapeutic targets. The copper transporter ATP7A has been implicated in cancer, but its precise role and regulatory mechanisms in HCC pathogenesis remain poorly understood. ATP7A expression was analyzed using public databases and validated in clinical HCC tissues and cell lines via qPCR and western blot. Functional assays were performed following ATP7A knockdown. Sensitivity to cuproptosis was assessed by measuring intracellular copper/ROS levels and IC50 of elesclomol-Cu. The upstream regulatory axis was identified through bioinformatic prediction and verified by dual-luciferase reporter and rescue experiments. The role of the LINC02038/miR-506-3p/ATP7A axis was further confirmed both in vitro and in a xenograft mouse model. ATP7A was significantly upregulated in HCC tissues and cell lines. ATP7A knockdown markedly inhibited HCC cell proliferation, migration, and invasion, while simultaneously sensitizing cells to cuproptosis. Mechanistically, LINC02038, which was highly expressed in HCC, functioned as a competing endogenous RNA (ceRNA) to sponge tumor-suppressive miR-506-3p, thereby upregulating ATP7A expression. This LINC02038/miR-506-3p/ATP7A axis was demonstrated to coordinately regulate malignant phenotypes and the expression of key cuproptosis-related proteins (DLAT, FDX1, LIPT1). In vivo, silencing LINC02038 effectively suppressed tumor growth and recapitulated the molecular alterations of this axis and cuproptosis regulators. Our findings reveal that the LINC02038/miR-506-3p/ATP7A axis played a crucial oncogenic role in HCC by driving tumor progression and modulating cuproptosis. This axis represents a promising prognostic biomarker and a potential therapeutic target for HCC intervention.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A-methylated circFANCB Promotes Gastric Cancer Progression by Regulating Cellular Ferroptosis Through miR-454-3p/CEACAM5","authors":"Haifeng Wang,&nbsp;Yan Li,&nbsp;Tiantian Sun,&nbsp;Man Su,&nbsp;Wei Dai,&nbsp;Zhihui Jin,&nbsp;Hangchen Shen,&nbsp;Changyu Jin,&nbsp;Yan Gao","doi":"10.1002/jbt.71022","DOIUrl":"10.1002/jbt.71022","url":null,"abstract":"<p>Gastric cancer (GC) is a major global digestive malignancy with high incidence and mortality. Circular fanconi anemia complementation group B (circFANCB) expression is elevated in cancer, and its suppression suppresses tumor progression. However, research on the function of circFANCB in GC has not been reported yet. The role and mechanism of circFANCB in GC were investigated through circular RNA (circRNA) sequencing, database prediction, and experimental validation, including quantitative real-time PCR (qRT-PCR), ribonuclease R assay, nuclear-cytoplasmic fractionation, 5-ethynyl-2′-deoxyuridine assay, flow cytometry, wound healing assay, Transwell assay, tube formation assay, western blot, dual-luciferase reporter assay, and enzyme-linked immunosorbent assay. Furthermore, its mechanism was further explored in vivo using a xenograft nude mouse model and immunohistochemistry. Online prediction tools, methylation-dependent RNA immunoprecipitation (MeRIP), and RNA immunoprecipitation (RIP) assays were employed to investigate whether methyltransferase-like protein 3 (METTL3) targeted circular FANCB (circFANCB) via m6A methylation. In GC, circFANCB expression was upregulated. Knockdown of circFANCB inhibited cell proliferation, migration, invasion, and angiogenesis while promoting cell death. CircFANCB increased CEACAM5 expression by binding to miR-454-3p. CEACAM5 suppressed ferroptosis in GC cells. Rescue experiments confirmed that circFANCB inhibited ferroptosis by upregulating CEACAM5, thereby promoting GC cell proliferation. Animal models demonstrated that circFANCB knockdown inhibited GC tumor growth. Additionally, METTL3 enhanced circFANCB expression through m6A methylation. Rescue experiments further confirmed that METTL3 promotes the malignant phenotype of GC cells by upregulating circFANCB. The m6A-modified circFANCB promotes the malignant progression of GC by regulating ferroptosis via the miR-454-3p/CEACAM5 axis, providing a theoretical basis for potential clinical therapeutic strategies.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond a Metabolite: Lactylation as a Pivotal Regulator of Colorectal Cancer Pathogenesis and Treatment Resistance","authors":"Shuilan Yao,&nbsp;Yun Liang,&nbsp;Xinwen Liang,&nbsp;Qisheng Su,&nbsp;Xiaohong Li","doi":"10.1002/jbt.71035","DOIUrl":"10.1002/jbt.71035","url":null,"abstract":"<p>Colorectal cancer (CRC) is a highly lethal malignancy worldwide. Lactylation, which serves as a key metabolic-epigenetic bridge driving malignant progression, is involved in CRC development, metastasis, immunosuppression, and drug resistance. This review systematically outlines the biological functions of lactate and the molecular mechanisms of lactylation, with a particular focus on their regulatory roles in CRC. Key aspects are summarized, including the dynamic regulation by lactylation-related enzymes (“writers” and “erasers”) and potential therapeutic strategies targeting lactylation. Distinct from existing studies, this review further explores the clinical translational potential of targeting lactylation. From a toxicological perspective, it analyzes mechanisms of chemotherapy resistance and the toxicological considerations associated with targeted therapies. Core challenges in clinical translation, such as off-target toxicity, optimization of the therapeutic index, and low drug delivery efficiency—are also examined. By synthesizing the latest research advances in lactylation modification in CRC, this review provides a clear framework to inform and guide subsequent basic research and clinical translation efforts.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PERK Signaling Pathway Mediates the Hepatoprotective Effects of Naringenin Against Cadmium-Induced Liver Injury in Rats","authors":"Chengxiang Guo,&nbsp;Hao Ling,&nbsp;Mengmeng Gao,&nbsp;Yinan Hu,&nbsp;Jing Zhu,&nbsp;Jicang Wang","doi":"10.1002/jbt.71044","DOIUrl":"10.1002/jbt.71044","url":null,"abstract":"<p>Cadmium (Cd), a heavy metal element with extensive industrial applications, exhibits significant toxicological risks in biological systems (Zhu et al. 2019). Naringenin (Nar), a bioactive flavonoid possessing potent antioxidant properties, demonstrates ameliorative effects against Cd toxicity. 24 male SD rats were randomly allocated into four groups: Control group; Cd group; Cd + Nar group; Nar group. Determination of biochemical indicators, antioxidant indicators; reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the expression levels of related mRNA and protein. Cd exposure reduced rat body weight and increased liver-to-body weight ratio, along with elevations in ALT, AST, GSH, and MDA. Conversely, Cd + Nar treatment increased body weight, reduced liver organ coefficient, and decreased these biomarkers. HE staining revealed expanded hepatic sinusoids in the Cd group. RT-qPCR and Western blot showed Cd upregulated GRP78, PERK, and CHOP expression at both mRNA and protein levels, while Cd + Nar treatment attenuated these increases. Cd activates the PERK signaling pathway through ERS and causes liver damage. Nar can reduce liver toxicity. The mechanism may be related to the inhibition of PERK activation by Nar.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Efficacy of Orientin in Streptozotocin-Induced Type 1 Diabetes Model and Pancreatic Beta-TC6 Cells","authors":"Bengul Ozdemir Sarikaya,&nbsp;Seyit Ali Bingol","doi":"10.1002/jbt.71047","DOIUrl":"10.1002/jbt.71047","url":null,"abstract":"<p>Diabetes mellitus is a major endocrine disorder with rapidly increasing global prevalence and numerous systemic complications. Orientin, a flavonoid isolated from various medicinal plants, is known for its potent antioxidant and anti-inflammatory properties. This study evaluated the protective effects of Orientin in a streptozotocin (STZ)-induced type 1 diabetes model and in the pancreatic Beta-TC6 cell line. In the in vivo phase, 42 mice were randomly divided into seven groups, and diabetes was induced by a single intraperitoneal injection of STZ (160 mg/kg). Proinflammatory (IL-1β, IL-6) and anti-inflammatory (TGF-β, IL-10) cytokines were measured by ELISA. Pancreatic tissues were evaluated histopathologically (Masson's trichrome, Hematoxylin-eosin) and immunohistochemically (NF-κB p65), while oxidative stress parameters (SOD, CAT, GSH, and MDA) were analyzed. In addition, hepatic oxidative stress parameters were assessed, and liver tissues were examined using Periodic Acid–Schiff (PAS) staining. In vitro, the protective effects of Orientin against STZ-induced damage in Beta-TC6 cells were investigated. Apoptotic markers (Caspase-3, Caspase-9, Bax, and Bcl-2) were evaluated immunohistochemically, and pyroptotic markers (IL-1β and Caspase-1) were analyzed by ELISA. STZ-induced diabetes increased NF-κB immunopositivity, proinflammatory cytokines, and oxidative stress in pancreatic tissue. Orientin treatment reduced proinflammatory cytokines, increased anti-inflammatory cytokines, and improved oxidative stress parameters in both pancreatic and hepatic tissues. In Beta-TC6 cells, Orientin upregulated Bcl-2 and downregulated Bax, Caspase-3, Caspase-9, Caspase-1, and IL-1β levels. These findings suggest that Orientin protects against STZ-induced pancreatic damage by modulating oxidative stress, inflammation, apoptosis, and pyroptosis, supporting its potential as a therapeutic agent for preserving beta-cell integrity in diabetes.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin Reduces Alcohol-Related Cardiac and Liver Tissue Damage, Oxidative Stress, Inflammation, Apoptosis, and Thiol-Disulfide Imbalance in Rats","authors":"Cumaali Demirtas,&nbsp;Şahhan Kılıç,&nbsp;Mert Babaoğlu,&nbsp;Süha Asal,&nbsp;Elif Gökçe Tenekeci,&nbsp;Hakan Beyaztaş,&nbsp;Eray Metin Guler,&nbsp;Salime Pelin Erguven,&nbsp;Kubra Sevgin","doi":"10.1002/jbt.71036","DOIUrl":"https://doi.org/10.1002/jbt.71036","url":null,"abstract":"<p>Excessive alcohol consumption causes significant cardio-hepatic damage. This study investigated the effects of standard (10 mg/kg) and high (40 mg/kg) doses of atorvastatin on fibrosis, hypertrophy, apoptosis, inflammation, oxidative stress, mitochondrial-mediated apoptotic pathways, and thiol/disulfide balance in alcohol-induced heart and liver injury. Forty Sprague-Dawley rats were divided into five groups (<i>n</i> = 8; 4 male/4 female): Control (CONT), ALCOHOL (2.5 g/kg 20% ethanol i.p./28 days), ATOR (10 mg/kg o.g./28 days), ALCOHOL + ATOR (10 mg/kg o.g./28 days) and ALCOHOL+ hATOR (40 mg/kg o.g./28 days). Histopathologically, alcohol caused cardiac myocyte dilation, vacuolization, inflammation, and hepatic cord disruption. While standard ATOR partially improved tissue architecture (<i>p</i> &lt; 0.001), the ALCOHOL+ hATOR group showed the lowest severity. Alcohol exposure significantly increased apoptosis (Caspase-3, M30, M65), oxidative stress (TOS, OSI, MDA), ischemia (IMA), and inflammatory cytokines (IL-1β, TNF-α, HsCRP, Endothelin-1) across serum, heart, and liver samples, while decreasing TAS, total thiol, and native thiol levels (<i>p</i> &lt; 0.001 for all vs. CONT). Conversely, high-dose atorvastatin (ALCOHOL + hATOR) significantly reversed alcohol-induced toxicity by decreasing Caspase-3, M30, M65, TOS, OSI, MDA, TNF-α, HsCRP, Endothelin-1, and disulfide levels, while significantly restoring TAS, total thiol, and native thiol levels (<i>p</i> &lt; 0.001 vs. ALCOHOL). TAS was significantly higher in the ALCOHOL+hATOR group than the ALCOHOL + ATOR group (<i>p</i> &lt; 0.001). Despite marked improvements by hATOR, OSI, TOS, IL-1β, and HsCRP levels remained higher than CONT (<i>p</i> &lt; 0.001). High-dose atorvastatin (40 mg/kg) exerts robust pleiotropic, anti-apoptotic, and antioxidant cytoprotection. By preserving thiol-disulfide homeostasis and limiting inflammation, high-dose atorvastatin effectively mitigates alcohol-induced subchronic cardiac and hepatic injury.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148533911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}