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.

Testicular apoptosis is an obvious adverse effect of many chemotherapeutic agents.one of these chemotherapeutic drugs is 6-mercaptopurine (6MP) which has a powerful anticancer effect. On the contrary, it has an adverse effect on the male reproductive system. This study aimed to evaluate the prospective ameliorative effects of Royal Jelly (RJ) on 6MP induced testicular apoptosis and investigate the mechanistic pathway of protection. For this aim, forty male adult albino rats were divided into four equal groups (n= 10): control rats, RJ group (200 mg/kg.b.wt. of RJ for 30 day P.o.), 6MP group (5 mg/kg.b.wt of 6MP for 20 day P.o.), and RJ+6MP group pretreated with RJ (200 mg/kg.b.wt. for 10 day P.o.), and continued with 6MP (5 mg/kg.b.wt, P.o) for 20 day. After 30 days blood samples, epididymis and testis were collected to investigate sex hormones, sperm parameters, histological and molecular changes of testicular tissues, that include anti-oxidants activity, caspase-3, TNF-α, gene expression of Androgen receptors (AR) and P53 also protein concentration of PI3K, AKT, Nrf2 and HO1were estimated. The results of our study revealed that Pretreatment of Royal Jelly (RJ) abrogated 6MP induced spermatogenesis impairment by ameliorating sperm count, motility and morphology, regulating AR mRNA expression and sex hormones levels. RJ ameliorated testicular damage of 6MP exposed rats through restoring testicular antioxidant/oxidative redox, inhibiting caspase-3 activity and P53 mRNA expression as well as regulation of PI3K, AKT, Nrf2 and HO1 protein levels. Our data concluded that RJ protected testicular tissue from 6MP induced apoptosis by regulation PI3K/AKT pathway.

Testicular apoptosis is an obvious adverse effect of many chemotherapeutic agents.one of these chemotherapeutic drugs is 6-mercaptopurine (6MP) which has a powerful anticancer effect. On the contrary, it has an adverse effect on the male reproductive system. This study aimed to evaluate the prospective ameliorative effects of Royal Jelly (RJ) on 6MP induced testicular apoptosis and investigate the mechanistic pathway of protection. For this aim, forty male adult albino rats were divided into four equal groups (n= 10): control rats, RJ group (200 mg/kg.b.wt. of RJ for 30 day P.o.), 6MP group (5 mg/kg.b.wt of 6MP for 20 day P.o.), and RJ+6MP group pretreated with RJ (200 mg/kg.b.wt. for 10 day P.o.), and continued with 6MP (5 mg/kg.b.wt, P.o) for 20 day. After 30 days blood samples, epididymis and testis were collected to investigate sex hormones, sperm parameters, histological and molecular changes of testicular tissues, that include anti-oxidants activity, caspase-3, TNF-α, gene expression of Androgen receptors (AR) and P53 also protein concentration of PI3K, AKT, Nrf2 and HO1were estimated. The results of our study revealed that Pretreatment of Royal Jelly (RJ) abrogated 6MP induced spermatogenesis impairment by ameliorating sperm count, motility and morphology, regulating AR mRNA expression and sex hormones levels. RJ ameliorated testicular damage of 6MP exposed rats through restoring testicular antioxidant/oxidative redox, inhibiting caspase-3 activity and P53 mRNA expression as well as regulation of PI3K, AKT, Nrf2 and HO1 protein levels. Our data concluded that RJ protected testicular tissue from 6MP induced apoptosis by regulation PI3K/AKT pathway.