Taraxasterol Exerts Cytoprotective Effects Against Nicotine Toxicity in Leydig (TM3) and Sertoli (TM4) Cell Lines

Antioxidant efficacy of N-acetylcysteine against acrylamide-induced toxicity in Leydig cells by modulating p53/Bax/Caspase-3 pathway.

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.

8-gingerol from Zingiber officinale induces ER stress-mediated ferroptosis and apoptosis in ovarian cancer involving TRPV1 activation.

It is demonstrated that 8-gingerol induces coordinated apoptotic and ferroptotic cell death through a Ca2+-dependent ER stress mechanism, highlighting its potential as a novel therapeutic strategy for the treatment of ovarian cancer.

Ameliorative properties of citronellol against alcohol-induced toxicity in human embryonic kidney (HEK) cells

It is suggested that citronellol confers protective effects against ethanol-induced cytotoxicity in human embryonic kidney cells, potentially by enhancing cell viability, attenuating oxidative stress, and modulating apoptosis-related pathways.

DOSE-DEPENDENT PROTECTIVE EFFECTS OF IRISIN AGAINST BISPHENOL A-INDUCED OXIDATIVE STRESS AND CASPASE-3-MEDIATED APOPTOSIS IN AML12 HEPATOCYTES

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.

Total flavonoids from Ageratum conyzoides synergize with docetaxel to induce ferroptosis in prostate cancer cells via the NRF2/SLC7A11/GPX4 signaling pathway.

Prostate cancer is one of the most common malignant tumors in men, and its treatment faces numerous challenges. This study aims to investigate whether the combined treatment of Total Flavonoids from Ageratum conyzoides (TFG) and Docetaxel (DTX) can enhance the antitumor effect of DTX on prostate cancer cells by regulating the NRF2/SLC7A11/GPX4 signaling axis and inducing mitochondria-related ferroptosis. Cell viability was detected using the CCK-8 assay. Plate colony formation, scratch, and Transwell assays were used to evaluate proliferation, migration, and invasion, respectively. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. PCR-Array was used to screen differentially expressed genes. RT-PCR and Western blot were performed to measure ferroptosis-related gene and protein expression. Reactive oxygen species (ROS) levels were detected using DCFH-DA, mitochondrial membrane potential using JC-1, lipid peroxidation using BODIPY-C11, and cellular ultrastructure by transmission electron microscopy. To validate the mechanistic involvement of ferroptosis, rescue experiments were performed using Ferrostatin-1 (Fer-1, a ferroptosis inhibitor) and Z-VAD-FMK (a pan-caspase inhibitor). Pharmacological inhibitors ML385 (NRF2 inhibitor) and RSL3 (GPX4 inhibitor) were used to probe pathway causality. Key findings were further validated in LNCaP (AR-positive) prostate cancer cells. TFG and DTX dose-dependently inhibited PC3 cell viability and showed synergistic effects. The combination significantly suppressed colony formation, migration, and invasion, induced late apoptosis, and arrested the cell cycle in S phase. Mechanistically, the combination upregulated TF and HMOX1 while downregulating NRF2, SLC7A11, and GPX4 expression. Fer-1 significantly rescued combination-induced cell death (~ 70% recovery), while Z-VAD-FMK showed partial rescue (~ 30% recovery), confirming ferroptosis as the dominant mechanism with secondary apoptosis involvement. ML385 + DTX and RSL3 + DTX phenocopied the TFG + DTX effect, supporting that TFG acts upstream of NRF2 and GPX4 is a key downstream effector. BODIPY-C11 staining confirmed increased lipid peroxidation, which was blocked by Fer-1. These findings were validated in LNCaP cells, showing consistent synergistic inhibition and downregulation of GPX4 and NRF2. TFG enhances the antitumor effect of DTX in prostate cancer cells by inhibiting the NRF2/SLC7A11/GPX4 axis, inducing lipid peroxidation, and triggering mitochondria-associated ferroptosis. Pharmacological rescue and inhibitor studies confirm ferroptosis as the primary mechanism, with apoptosis playing a secondary role. These findings provide a strong mechanistic rationale for developing TFG as a natural chemosensitizer for prostate cancer therapy, particularly for overcoming DTX resistance.

Protective effects of thymoquinone against hexavalent chromium-ınduced nephrotoxicity: a multiparametric evaluation of oxidative stress, ınflammation, ferroptosis- and apoptosis-related markers