Possible mechanisms involved in the testicular-protective property of quercetin in rats exposed to endosulfan toxicity.

The study investigated the effects of quercetin and putative mechanisms involved against endosulfan-testicular impairments in rats. Rats were allotted into five treatment groups (n = 5). Groups 1-2 had normal saline and maize oil (vehicle) (10 mL/kg), group 3 received quercetin (20 mg/kg), 4-5 had endosulfan (5 mg/kg, p.o) orally for 28 days. However, from days 14-28, group 4 received an additional dose of vehicle (10 mL/kg, p.o./day), while group 5 received quercetin (20 mg/kg, p.o./day). Thereafter, blood samples and testes were harvested for markers of cholinergic, hormonal and testicular oxido-nitrergic, inflammatory, apoptosis and proton pump ATPase activities. Also, testicular histopathological changes were also evaluated alongside with germ cell count, testicular injury and spermatogenesis score. Quercetin increased testicular/body weights and spermatogenesis, androgenic hormones (follicle stimulating hormones, FSH; luteinizing hormone, LH; testosterone), acetylcholinesterase levels and attenuated altered membrane integrity, DNA fragmentation, increased caspases-3 levels in rats exposed to endosulfan. Moreover, quercetin increased testicular B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x-protein (Bax) and proton pump adenosine trisphosphate (ATPase) and sialic acid levels. Of note, quercetin reversed endosulfan-mediated increased malondialdehyde, nitrite, peroxynitrite formation, 8-hydroxy-2'-deoxyguanosine and lowered antioxidant enzymes in the testes. The increased levels of testicular myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) by endosulfan were also reduced by quercetin administration. Additionally, quercetin attenuate endosulfan-induced testicular histopathological changes of rats. Our findings showed that quercetin significantly inhibited endosulfan-induced testicular damage and altered spermatogenesis through inhibition of oxido-nitrergic pathway, inflammatory mediators, apoptosis, acetylcholinesterase activity and enhancement of testicular hormones and improvement in testicular ATPase activity.

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.

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 follicle-stimulating 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.