Thymoquinone Attenuates 6-Mercaptopurine Induced Testicular Toxicity in Albino Rats: Possible Mechanisms are Involved

The present study was conducted in order to investigate the efficacy of thymoquinone (TQ) to attenuated 6-mercaptopurine (6MP) induced testicular toxicity with insight into the mechanism(s) of protection. 6MP is an anti-cancer and immunosuppressant chemotherapeutic drug; however, it had a potent toxic effect in various body organs. Forty male adult albino rats were allocated into four equal groups: control rats, TQ(5 mg/kg.BW orally) for a month, 6MP (5 mg/kg.BW orally) for twenty days, and TQ+6MP group pretreated with TQ for ten days then coadministered with 6MP for twenty days. The oral gavage was persisted daily for 30 days followed by blood samples collection to estimate testosterone. Cauda epididymis was collected to evaluate sperm characteristics. Testes were collected to estimate histological architecture, biochemical and molecular changes of testicular tissues. 6MP treated rats showed a significant decrease in testicular weight, sperm concentration, motility and viability, serum testosterone and down-regulation in Androgen receptors (AR) mRNA, as well as, histological alteration, a significant depletion in testicular catalase and Glutathione reduced (GSH) with increasing in Malondialdehyde (MDA) levels. 6MP induced upregulation in P53 gene expression and caspase-3 activity with a down-regulation in phosphoinositide 3-kinase (PI3K). Co-treatment of TQ with 6MP improved spermatogenesis, testis histology, restoring testicular antioxidant/ oxidative redox, inhibiting P53, caspase-3 apoptotic pathway and up-regulated PI3K. TQ exerts its therapeutic effect against 6MP-induced testicular damage and dysfunction through anti-oxidative and anti-apoptotic pathways.