Protective effect of diallyl sulfide against lead-mediated oxidative damage, apoptosis and down-regulation of CYP19 gene expression in rat testes

Aims: The present study aimed to investigate the potential therapeutic effect of diallyl sulfide (DAS), a natural component of garlic (Allium sativum), in the improvement of lead (Pb)-induced testicular toxicity and its underlying mechanisms. Materials and methods: Thirty-two male albino rats were randomly divided into control, PbAc (20 mg lead acetate/kg bwt, orally), DAS (200 mg/kg bwt, orally), and PbAc+ DAS groups for 49 successive days. The investigation based on the following criteria: Paired testes and epididymides weights, epididymal sperm analysis, level of serum sex hormones (Testosterone and17 beta-estradiol (E2)), aromatase (CYP19) expression, Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD) enzyme, reduced glutathione (GSH), testicular histopathology, spermatogenesis score and apoptosis detection (Caspase-3 immunoexpression). Key findings: Pb caused significant decline in epididymal sperm count and motility, testes and epididymes weights, spermatogenesis score and serum testosterone and 1E2, as well as a significant decrease in SOD and GSH level, and a significant elevation of MDA and NO compared to a control group. In addition, Pb induced significant downregulation of CYP19 gene expression, increase of Caspase-3 immunoreactivity, various testicular degenerative and necrotic changes. Whereas, co-treatment of rats with DAS improved sperm analysis, and testicular histology and antioxidative status. Furthermore, DAS co-administration regulated testicular CYP19 and Caspase-3 expressions. Significance: Collectively, DAS seemed to be a promising agent for protection against Pb-induced testicular toxicity through antioxidative properties, beside regulation of testicular apoptosis and aromatase expression.