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.

AIM

The present study investigated the role of redox balance, inflammation, 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 inflammation and apoptosis.

RESULTS

Tra caused a significant 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 significant inhibition of anti-apoptotic Bcl-2 expression, besides a significant increase in pro-apoptotic Bax expression. There was a significant 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 inflammatory and apoptotic pathways (Tab. 4, Fig. 5, Ref. 63).