Effects of tramadol administration on male reproductive toxicity in Wistar rats: The role of oxidative stress, mitochondrial dysfunction, apoptosis-related gene expression, and nuclear factor kappa B signalling

Abstract

AIM: The present study investigated the role of redox balance, infl ammation, mitochondrial dysfunction, and apoptosis in Tramadol (Tra)-induced testicular toxicity. METHOD: Twenty-four male Wistar rats were randomly divided into either the control group or the groups receiving different doses of Tra (25, 50, and 75 mg/kg/day, i.p.) for 21 successive days. Testicular tissues were collected for oxidative stress, mitochondrial function, sperm assays and histopathological evaluation. Real-time polymerase chain reaction was performed to evaluate the markers of infl ammation and apoptosis. RESULTS: Tra caused a signifi cant reduction in the sperm count, motility and morphology, while it caused a marked increase in oxidative stress parameters. In addition, Tra induced testicular mitochondrial dysfunction due to the collapse of mitochondrial membrane potential and mitochondrial swelling. It also led to the signifi cant inhibition of anti-apoptotic Bcl-2 expression, besides a signifi cant increase in pro-apoptotic Bax expression. There was a signifi cant increase in the level of tumour necrosis factor-α, interlukin-1β and nuclear factor kappa B. Histopathological degenerative changes were observed in the testis after Tra exposure. CONCLUSIONS: The present results suggest that Tra exposure may lead to reproductive toxicity due to the loss of the antioxidant defence system, mitochondrial dysfunction, and activation of infl ammatory and apoptotic pathways (Tab. 4, Fig. 5, Ref. 63). Text in PDF www.elis.sk.