d‐ribose‐l‐cysteine abrogates testicular maladaptive responses induced by polychlorinated bisphenol intoxication in rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, inflammation, and oxidonitrergic flux

Abstract

Male reproductive maladaptive responses are becoming a global health concern and also a social issue. Polychlorinated biphenyls (PCBs) are a member of halogenated aromatic environmental pollutants with diverse environmental matrices. This study was conducted to explore the mechanisms of PCBs-induced testicular maladaptive responses and the potential reversal effects of D-ribose-L-cysteine (DRLC) on testicular injury induced by administration of PCBs (2 mg/kg) for 30 days. DRLC (50 mg/kg) was administered orally for 15 days starting from Days 16 to 30 after the initial 15 days of treatment with PCB. All assays were carried out using established protocols. Administration of DRLC at 50 mg/kg after treatment with PCBs enhances body and testicular weights, gonadotropins (luteinizing hormone and folliclestimulating hormone), testosterone and poor sperm quality. DRLC also reduced testicular injury score, improved spermatogenesis scoring, reduced oxidative stress biomarkers (malondialdehyde), as well as restored the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and decreases pro-inflammatory response (tumor necrosis factor-alpha and NO). More so, DRLC treatment abrogates testicular DNA fragmentation and downregulated p53 and caspase 3 activities and upregulated the concentration of autophagy-related protein (mammalian target of rapamycin [mTOR] and Atg7). DRLC abates testicular deficit induced by PCBs intoxicated rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, Inflammation and oxidative flux.

Diosmin protects the testicles from doxorubicin-induced damage by increasing steroidogenesis and suppressing oxido-inflammation and apoptotic mediators

“…Anti-carcinogenic medications are gonadotoxic and spermatotoxic [35][36][37], notably causing oxidative stress, apoptosis, and immunological changes in reproductive cells [38]. Natural antioxidant flavonoids with gonadoprotective actions have been employed to alleviate these negative effects [31,32,39]. Hence, our study examined rats treated with DOX (3 mg/kg) intraperitoneally at intervals of 7 days.…”

“…BioVision, Sigma-Aldrich, and Cusabio ELISA kits were used to assess B-cell lymphoma-2 and testicular caspases 3 and 9 using indirect analysis of mitochondrial cytochrome C. Oyovwi et al [32] used spectrophotometry at 550 and 540 nm to identify mitochondrial cytochrome C in the supernatants.…”