Exploring the neuroprotective potential of losartan against acrylamide-induced oxidative stress and apoptosis in PC12 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.

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.

p-Coumaric Acid Attenuates Lead Acetate-induced Neurotoxicity in Rats by Improving Behavioral Dysfunction and Suppressing Oxidative Stress, Neuroinflammation, Apoptosis, and Plasticity-related Molecular Alterations.

Hesperidin Attenuates Deltamethrin-Induced Testicular Damage by Modulating Apoptosis-Associated Signaling and Profibrotic Gene Expression: Biochemical, Molecular, and Histological Evidence

This study aimed to investigate the effect of hesperidin (HSP) at two different doses on deltamethrin (DLM)-induced testicular damage. The study comprised four groups of Wistar Albino rats (n = 8 per group): Control, DLM, DLM + HSP 100 mg/kg, and DLM + HSP 300 mg/kg. At the end of the study, oxidative stress markers and CRP were measured in serum samples. Testicular tissues were assessed histopathologically. Expression of Bcl-2, Bax, and Nrf-2 were determined by immunofluorescence staining. RT-qPCR assessed tissue collagen (COL1A1, COL3A1) and apoptotic () expressions. HSP at both doses lowered the DLM-induced increase in total oxidant status, oxidative stress index (total oxidant status/total antioxidant capacity), and CRP levels. Nrf-2 was increased by a high dose of HSP (300 mg/kg). Whereas HSP normalized other apoptotic parameters at both doses, it partially normalized Bax expression in immunofluorescence and Bcl-2 expression in RT-qPCR only at 300 mg/kg. HSP reduced the increased fibrosis in DLM exposure, as revealed by the expressions of COL1A1 and COL3A1 at both doses. HSP partially ameliorated DLM-associated histological alterations, including Johnsen’s score, tubule diameter, and thickness of the tunica albuginea. HSP may exert protective effects against DLM-induced testicular injury by modulating systemic oxidative status, apoptosis-associated signaling, and profibrotic gene expression.

Hesperidin mitigates DEHP-induced nephrotoxicity through anti-oxidant, anti-apoptotic, and anti-inflammatory pathway modulation: Evidence from Nrf2/HO-1/Keap-1, Bax/Bcl-2/caspase-3, and TLR4/NF-κB axis activation

Objective(s): This study aimed to assess the protective role of hesperidin (HSP), a citrus flavonoid, against di-(2-ethylhexyl) phthalate (DEHP)-induced kidney toxicity in rats, focusing on oxidative stress, apoptosis, inflammation, and anti-oxidant defense pathways. Materials and Methods: Thirty-five male rats were randomly assigned into five groups (7 per group): control group, DEHP-treated group (1 g/kg), DEHP + HSP (100 mg/kg) group, DEHP + HSP (200 mg/kg) group, and HSP-alone group, and treated orally for 10 consecutive days. Kidney tissues were collected for biochemical assays, including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Gene expression of Nrf2, Keap1, HO-1, Bax, Bcl-2, Caspase-3, TLR-4, and NF-κB was analyzed using real-time PCR, and protein levels were evaluated using Western blotting. Results: DEHP significantly increased oxidative damage and the expression of inflammatory and apoptotic markers, while decreasing anti-oxidant parameters. Co-treatment with HSP, particularly at 200 mg/kg, restored anti-oxidant balance, reduced lipid peroxidation, and down-regulated the expression of TLR-4, NF-κB, and Caspase-3. Moreover, HSP increased Bcl-2 levels and enhanced Nrf2/HO-1 signaling, as confirmed by both gene and protein expression data. Conclusion: HSP demonstrates dose-dependent renoprotective effects against DEHP-induced nephrotoxicity in rats. The protective mechanism involves anti-oxidant enhancement and inhibition of oxidative stress-induced inflammation and apoptosis, supporting the therapeutic potential of HSP in managing phthalate-related renal injury.

Barbaloin Attenuates Cisplatin‐Induced Hippocampal Neurotoxicity by Suppressing Oxidative Stress, Neuroinflammation, and Apoptosis: In Vivo and In Silico Evidence

The neurotoxicity of cisplatin (CIS) in the hippocampal leads to cognitive effects caused by oxidative stress, neuroinflammation, apoptosis, and dysfunction of neurotransmitters. The major bioactive phytonutrient in Aloe vera is barbaloin (BLN), which has been shown to have antioxidant and anti‐inflammatory effects, but its neuroprotective ability against CIS‐induced neurotoxicity has not been investigated. To assess the neuroprotective action of BLN in CIS‐induced hippocampal neurotoxicity in rats and to understand the molecular interactions between BLN and major neuroinflammatory and apoptotic proteins. A total of 24 male Wistar rats were split into 4 groups (n = 6): control, CIS (5 mg/kg), CIS + BLN 25 mg/kg, and CIS + BLN 50 mg/kg over 21 days. Cognitive ability (Morris water maze), oxidative stress indicators (MDA, GSH, SOD, CAT), neuroinflammatory cytokines (TNF‐α, IL‐1β, IL‐6, NF‐κB, TGF‐β1), caspase‐3, neurotransmitters, and hippocampal histopathology were measured. Molecular docking and 100‐ns molecular dynamics simulations (MDS) with MM‐GBSA analysis were done with TNF‐α, TGF‐β1, NF‐κBp65, and caspase‐3. BLN significantly reduced cognitive impairment, oxidative stress, neuroinflammation, and apoptosis, and restored neurotransmitter homeostasis and hippocampal cytoarchitecture (all p < 0.0001). Molecular docking demonstrated positive binding energies (− 7.226 to −8.566 kcal/mol), and MDS revealed the presence of stable BLN–protein complexes (ΔGbind = −56.07 kcal/mol for TGF‐β1). BLN exhibits considerable neuroprotective properties against CIS‐induced neurotoxicity in the hippocampus, suggesting its potential as a natural dietary phytonutrient supplement to ameliorate chemotherapy‐induced cognitive impairment.