Jul 2026· Eskişehir Teknik Üniversitesi Bilim ve Teknoloji Dergisi - C Yaşam Bilimleri Ve Biyoteknoloji· 0 citations· 27 references
TL;DR
It is found that irisin alleviated BPA-induced hepatotoxicity by mitigating oxidative stress and caspase-3-mediated apoptosis, implying that irisin may represent a potential therapeutic candidate for the treatment of toxin-induced liver injury.
Abstract
Bisphenol A (BPA) is a widespread environmental contaminant that causes hepatotoxicity through oxidative stress and apoptosis. In the present study, the dose-dependent protective effect of irisin against BPA-induced hepatotoxicity in AML12 hepatocytes was evaluated. AML12 hepatocytes were treated with BPA (100 µM) with or without irisin (50 and 100 nM). Cell viability was measured by MTT test and cytotoxicity was measured by lactate dehydrogenase (LDH) release. The oxidative status of the cells was characterized by evaluating malondialdehyde (MDA) levels, total oxidant status (TOS), total antioxidant status (TAS), and superoxide dismutase (SOD) activity. In addition, the oxidative stress index (OSI) and caspase-3 activity were assessed to provide insight into cellular redox balance and apoptotic responses. BPA significantly reduced cell viability and antioxidant capacity, and increased LDH release, lipid peroxidation and apoptotic activity. However, irisin significantly ameliorated these changes in a dose-dependent manner. More specifically, irisin significantly decreased MDA, TOS, OSI, and caspase-3 activity and increased SOD activity and TAS levels, and cell viability. The higher dose of irisin (100 nM) was more effective than the lower dose. This study found that irisin alleviated BPA-induced hepatotoxicity by mitigating oxidative stress and caspase-3-mediated apoptosis, implying that irisin may represent a potential therapeutic candidate for the treatment of toxin-induced liver injury.
Acrylamide (Acr) is a widely encountered environmental and dietary toxicant known to induce oxidative stress and disrupt male reproductive function. Leydig cells, due to their high metabolic activity and mitochondrial dependence, are particularly vulnerable to redox imbalance. N-acetylcysteine (Nac), a thiol-containing antioxidant and glutathione precursor, has been extensively studied for its cytoprotective properties. However, its modulatory effects on Acr-induced toxicity in Leydig cells and its pharmacodynamic interaction profile remain incompletely characterized. In this study, TM3 Leydig cells were exposed to Acr in the presence or absence of Nac. Cell viability was assessed by MTT assay, and chemical interaction profiles were evaluated using ZIP, Bliss, and Chou-Talalay combination index analyses. Oxidative stress parameters, including intracellular reactive oxygen species (ROS), lipid peroxidation, antioxidant enzyme activities (SOD, CAT, GPx), and glutathione levels, were measured. Apoptotic responses were analyzed through double fluorescence staining, RT-qPCR of apoptosis-related genes (Bax, Bcl2, Casp3, Trp53), and Western blot analysis of CASP3 protein expression. Acr exposure significantly reduced cell viability, increased ROS and lipid peroxidation levels, suppressed antioxidant defenses, and activated the mitochondrial apoptotic pathway. Nac treatment markedly improved cell viability, restored antioxidant capacity, reduced oxidative stress markers, and suppressed p53/Bax/Casp3-mediated apoptotic signaling. Combination analyses revealed an antagonistic interaction profile, indicating that Nac biologically limits Acr-induced cytotoxicity. Collectively, these findings demonstrate that Nac exerts protective effects in Leydig cells by modulating redox homeostasis and mitochondrial apoptosis, suggesting its potential as a protective regulator against Acr-induced reproductive toxicity.
Banu Orta Yilmaz, Iremnur Sarialioglu, Gokce Elmaci et al.· Drug and chemical toxicology...· 0 citations
Bavachinin exhibited anti-inflammatory and pro-apoptotic activities against HeLa cells, likely through oxidative stress-associated apoptosis and modulation of NF-κB-associated inflammatory gene expression.
Genistein (GEN) exhibits concentration- and cell-type-dependent biological activities; however, the mechanisms underlying its cytotoxicity remain incompletely understood. This study investigated whether oxidative stress-mediated mitochondrial dysfunction contributes to GEN-induced apoptosis in TM4 mouse Sertoli cells and ELT3 rat leiomyoma cells. Cells were exposed to GEN (30 or 100 µM) for 48 h. Cytotoxicity, oxidative stress, mitochondrial function, and apoptosis were assessed by measuring cell viability, lactate dehydrogenase release, reactive oxygen species (ROS), malondialdehyde, glutathione reductase activity, mitochondrial membrane potential (ΔΨm), intracellular ATP, apoptosis-related gene expression, and caspase-3/-9 activities. The involvement of oxidative stress was examined using N-acetyl-L-cysteine (NAC). GEN reduced cell viability, antioxidant capacity, ΔΨm, and ATP content while increasing membrane damage, ROS accumulation, and lipid peroxidation in both cell lines. These changes were accompanied by upregulation of Bax, Tp53, caspase-3, and caspase-9; downregulation of Bcl-2; and increased caspase-3/-9 activities. NAC pretreatment attenuated these alterations, supporting ROS as an upstream mediator. Notably, TM4 cells were approximately 4.4-fold more sensitive to GEN than ELT3 cells at 48 h. Collectively, the findings support a ROS-dependent mitochondrial apoptotic response under elevated in vitro GEN exposure but do not establish selective antitumor cytotoxicity or direct physiological relevance.
Samak Sutjarit, C. Sakulthaew, Nattakan Meekhanon et al.· Journal of Xenobiotics· 0 citations
Overall, the findings indicate that Que mitigates PdCl₂-induced testicular injury, and that this protection may be associated with antioxidant, anti-inflammatory, anti-apoptotic, ER stress-related, and Nrf2/HO-1-associated responses rather than direct proof of pathway activation.
Doxorubicin (DOX) is a highly effective anthracycline chemotherapeutic agent whose clinical utility is limited by dose-dependent cardiotoxicity. Although oxidative stress and mitochondrial injury are established mechanisms, the contribution of regulated metal-dependent cell death (MCD) pathways remains incompletely defined. This study investigated the ferroptosis and cuproptosis role in doxorubicin-induced cardiotoxicity (DIC) and evaluated the protective effects of luteolin (LUT) and nanoliposomal LUT using an integrated network pharmacology and experimental validation approach in rats. Network pharmacology identified multitarget interactions linking LUT with oxidative stress, metal homeostasis, and cell death signaling pathways. In vivo, DOX administration induced marked cardiac dysfunction, elevated serum cardiac injury biomarkers, myocardial histopathological damage, and ultrastructural abnormalities. These changes were accompanied by significant cardiac iron and copper accumulation, increased malondialdehyde (MDA), depleted superoxide dismutase (SOD) and glutathione (GSH), reduced glutathione peroxidase-4 (GPX4) activity, and increased tumor protein p53 (TP53) expression. At the molecular level, DOX downregulated the ferroptosis-protective genes, SLC7A11 and SLC3A2, while upregulating the iron transport genes, transferrin receptor 1 (TFR1) and SLC39A14, together with the cuproptosis-related genes ferredoxin-1 (FDX1) and SLC31A1, while suppressing ATP7A. These changes were further supported by altered protein expression of SLC7A11, ATP7A, and TP53. LUT significantly ameliorated these functional, biochemical, molecular, and structural alterations, indicating suppression of both ferroptotic and cuproptotic signaling. Nanoliposomal LUT showed superior efficacy to free LUT across most assessed parameters. Collectively, these findings support the involvement of ferroptosis and cuproptosis related signaling in DIC and highlight LUT, particularly in nanoliposomal form, as a promising cardioprotective strategy against anthracycline toxicity.
Amina A. Farag, W. E. El gazzar, Mahmoud Mostafa et al.· Biomedicine & pharmacotherap...· 0 citations