Neurodegeneration and oxidative stress induced by tramadol administration in male rats: The effect of its withdrawal

Abstract

The purpose of this study was to evaluate the possible neurodegeneration and oxidative stress induced bytramadol administration in male rats. One hundred male albino rats were divided into three groups. Group I(normal control): consisted of twenty rats, administered saline solution. Group II (therapeutic dose gp): fortyrats, received oral dose of tramadol HCl suspended in saline solution equivalent to 22.5 mg/kg/day for nineweeks; ten rats were left for further two weeks without any additional treatment as a recovery period. GroupIII (over- dose gp): forty rats, received oral dose of tramadol HCl suspended in saline solution at doses of 30,60 and 90 mg/kg/day on the first, the second and the third three weeks of the study, respectively; ten ratswere left from Group III for further two weeks without any additional treatment as a recovery period. Theobtained results showed significant increase in serum liver marker enzyme (ALT and AST) activities, andbrain tissue MDA, NO, DNA fragmentation, 8-OHdG and caspase-3 in both tramadol therapeutic and overdosegroups. However, brain tissue antioxidant enzyme (SOD and CAT) activities were markedly decreased.Tramadol withdrawal for two weeks produced significant improvement of all previous parameters towardsits normal ranges. These results proved that, tramadol administration for 9 weeks induced liver dysfunctionand brain injury in rats, as well as a degenerating endogenous antioxidant defense system mechanism. Thesefindings are of importance to be considered in patients who use tramadol as a pain killer, especially in thelong term conditions.