Some Toxicological and Histopathological Changes Induced By Long- Term Administration of Tramadol in Male Rats

Abstract

The present study investigated the effects of repeated tramadol administration on 60 male rats. The animals were randomly divided into 6 equal groups (n=10/group). The first group served as control and received saline solution only during the study. the second, third, fourth , fifth and sixth groups were given oral doses of tramadol ( tramadol HCL) suspended in saline solution equal to 40, 80, 120,160 and 200 mg/kg daily for 60 days. Liver and kidney functions, sex hormones activity, some neurochemical parameters in addition to some histopathological changes of the rat testis and brain tissues were studied. The results of the present experiment revealed a significant gradual increase in the serum ALT, AST and creatinine by increasing the dose of tramadol, the same result was obtained for PRL and E2 in male rats. Tramadol significantly reduced serum LH, FSH and testosterone levels gradually, where 200 mg/kg showed the lowest levels. Repeated administration of tramadol also increased the density of α1–adrenoceptors in the rat brain cortex, as measured by saturation analysis of [3H]prazosin binding resembling the effects induced by conventional antidepressants. The histopathological examination of testis revealed severe diffused testicular degeneration, which was aggravated till testicular tissues calcification with increasing dose of tramadol (40, 80, 120, 160 and 200 mg/ kg.b.wt.). Brain tissues in all treated groups showed slight congestion of sub-meningeal blood vessels and neural degeneration. These findings suggest increased hepatic, renal and neurological damage and sexual dysfunction evoked by repeated administration of tramadol for long periods.