Chronic Addiction to Tramadol and Withdrawal Effect on the Spermatogenesis and Testicular Tissues in Adult Male Albino Rats

Abstract

Aim: The present study aimed to elucidate the effects of tramadol on the testicular functions of adult male rats due to the chronic usage of tramadol and the effect of its withdrawal.

Method: Adult male albino rats were classified into the following 3 groups: (I) a control administered with normal saline and (II) tramadol-treated rats (40 mg/kg b.w. orally) for 21 successive days; and (III) like the rats in the second group but kept for 4 weeks after the last tramadol dose to study the effect of tramadol withdrawal. At the end of the experimental period, blood was collected and specimens from testis were taken for histopathological, biochemical, and molecular studies. A reverse transcription-polymerized chain reaction after RNA extraction from specimens was detected for the anti-apoptotic and pro-apoptotic genes in testicular tissues. Also, malondialdehyde (MDA) was measured in tissues homogenate and antioxidant enzymes activities were evaluated.

Results: The results of this study demonstrated histological changes in testicular tissues in groups II and III compared to the control group, accompanied with increased apoptotic index and proved by increased B-cell lymphoma-2 (Bcl-2) associated-X-protein and caspase-3 expression, whereas anti-apoptotic Bcl-2 markedly decreased. Moreover, in tramadol-abused and -withdrawal groups, the MDA level increased, while the antioxidant enzymes activity decreased and revealed oxidative stress, indicating that tramadol is harmful at the cellular level and can induce apoptotic changes in testicular tissues. The withdrawal effect showed signs of improvement, but it did not return to normal levels.

Conclusions: It could be concluded that the administration of tramadol causes abnormalities on testicular tissues associated with oxidative stress, which confirmed the risk of increased oxidative stress on testicular tissues due to tramadol abuse.

Keywords: Apoptosis; B-cell lymphoma-2; B-cell lymphoma-2 associated-X-protein; Caspase-3; Oxidative stress; Testis; Tramadol.