Thymoquinone attenuates testicular and spermotoxicity following subchronic lead exposure in male rats: Possible mechanisms are involved

Aims: The testis is one of the main target organs for lead (Pb) toxicity. The current study was investigated the mechanism (s) of the therapeutic potential of thymoquinone (TQ), the active principle of Nigella sativa seed, against testicular toxicity following subchronic Pb exposure in the light of cytopathic effects, apoptotic signaling pathways, oxidative stress, serum sex hormones levels and testicular aromatase gene expression. Materials and methods: Thirty-two male albino rats were randomly allocated into control, PbAc (20 mg PbAc/kg bwt, orally), TQ (5 mg TQ/kg bwt dissolved in corn oil, orally), and PbAc + TQ groups for 56 successive days. Key findings: PbAc-treated rats showed significant decrease of testes and epididymes weights, sperm count, motility and viability, spermatogenesis score and serum FSH, LH, testosterone and estradiol levels, as well as a significant decreased testicular antioxidant molecules (Superoxide dismutase enzyme and reduced glutathione), and a significant elevation of sperm abnormalities, oxidative biomarkers (Malondialdehyde and Nitric oxide) compared to a control group. In addition, Pb induced significant downregulation of aromatase gene expression, activation of Bax and Caspase-3 apoptotic pathways. Moreover, Pb caused complete seminiferous tubules hyalinization (38%), germinal epithelium sloughing (15%) and hypocellularity (8%). However, administration of TQ with PbAc improved sperm quality, testicular histology and oxidative/antioxidative status, and serum levels of LH, testosterone and E2 with respect to PbAc group. Additionally, TQ with PbAc significantly lessen the staining intensity and the area of Bax and Caspase-3 immunoexpression. Significance: TQ might exert its acceptable therapeutic potential against Pb-induced testicular and spermotoxicity via anti-oxidative, endocrine and anti-apoptotic pathways.