Redox-dependent cytoprotection by zerumbone via Nrf2-Keap1 mediated restoration of antioxidant and apoptotic balance in Mancozeb-exposed cells.

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.

Dendrobine activates the SIRT3-SOD2 axis to protect keratinocytes from UVB-induced oxidative damage.

BACKGROUND Ultraviolet B (UVB) irradiation is a primary environmental factor leading to skin oxidative damage and photoaging, primarily by disrupting mitochondrial redox homeostasis in keratinocytes. Dendrobine (DDB), a bioactive sesquiterpene alkaloid derived from the edible and medicinal plant Dendrobium nobile, exhibits diverse pharmacological properties. However, its role and mechanism in protecting against UVB-induced skin damage remain unclear. MATERIALS AND METHODS HaCaT human keratinocytes were pretreated with DDB (5-20 μM) prior to UVB irradiation (160 mJ/cm2). Cell viability was assessed using MTT and crystal violet staining assays. Oxidative stress markers, including reactive oxygen species (ROS), 4-hydroxy-2-nonenal (HNE), protein carbonyls, and glutathione (GSH/GSSG) ratio, were measured. Apoptosis was evaluated by flow cytometry, and expression of apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3, and cleaved caspase-9) and mitochondrial regulators (SIRT3 and SOD2) was analyzed by western blotting. SIRT3 and SOD2 enzymatic activities were determined using commercial kits. Surface plasmon resonance (SPR) and molecular docking were employed to assess direct binding between DDB and SIRT3. Pharmacological inhibition with 3-TYP was used to establish SIRT3 dependency. RESULTS DDB significantly rescued HaCaT cells from UVB-induced viability loss in a concentration-dependent manner. DDB attenuated UVB-induced oxidative stress, as evidenced by reduced ROS, HNE, and protein carbonyl levels, and restored the GSH/GSSG ratio. DDB suppressed apoptosis by decreasing Bax/Bcl-2 ratio and cleaved caspase-3/9 levels. Mechanistically, DDB restored UVB-inhibited enzymatic activities of SIRT3 and SOD2 and upregulated their protein expression. SPR analysis revealed that DDB directly binds to SIRT3 with micromolar affinity (KD = 7.603 × 10-6 M). Molecular docking predicted that DDB binds within a distinct pocket of SIRT3 without competing with its substrate peptide. Critically, pharmacological inhibition of SIRT3 with 3-TYP abolished DDB's protective effects against oxidative damage. CONCLUSION This study demonstrates that DDB protects keratinocytes from UVB-induced oxidative damage and apoptosis by directly activating the SIRT3-SOD2 axis, thereby restoring mitochondrial redox homeostasis. These findings establish DDB as a promising natural candidate for functional foods or pharmaceuticals aimed at preventing skin photoaging and preserving mitochondrial function.

Bavachinin induces oxidative stress-associated apoptosis and modulates NF-κB-associated inflammatory gene expression in cervical cancer cells

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.

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.

IMD-1 Protects SH-SY5Y Cells Against H2O2-Induced Oxidative Injury Through Modulation of Oxidative Stress, Mitochondrial Bioenergetics, Inflammatory Mediator Release, and Apoptosis-Related Responses

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.