Abstract
Several deleterious effects of Tramadol including deaths were reported especially when used in large doses. Being metabolized mainly in the liver, Tramadol have serious hepatotoxic effects. This study investigates the effect of vitamin E on Tramadol-induced hepatotoxicity in rats by evaluating the antioxidant biochemical markers, the histopathological and immunohistochemical changes.Thirty adult mature male albino rats were divided into five groups (Gs); G1: negative control; G2: received Tramadol 150 mg/kg, G 3-5: received Tramadol plus vitamin E in concentrations of 50 mg/kg, 100 mg/kg and 200 mg/kg respectively. Liver function parameters and oxidative markers in liver tissue (CAT, SOD, GSH, and MDA) were estimated. Liver samples were processed for histopathological and immunohistochemical (Caspase 3 and TNF) examinations. The results indicated that Sub-chronic administration of Tramadol resulted in impaired liver functions, increased oxidative stress parameters with decreased antioxidant capacity of liver tissues, severe hepatocellular damage (hydropic degeneration, steatosis and apoptosis) and strong immunoexpression to TNF and Caspase 3. All these effects were ameliorated with concomitant administration of vitamin E especially with high doses. The co-treatment of Tramadol-intoxicated rats with Vitamin E, especially in high doses, protects against hepatic toxicity.