Antioxidant effects of vitamin E on diclofenac induced hepatotoxicity in male rats

Drug induced liver injury possesses a major clinical problem and has become leading cause of acute liver failure and transplantation. Overstressed liver compromises its detoxification role which may expose it to a variety of diseases and disorders. The present study was to determine whether pre- administration of various doses of vitamin E would have protective effect against diclofenac induced hepatotoxicity in wistar male rats. Twenty-four albino male rats weighing 180-200g were divided equally into four groups. In control group rats were administrated with physiological saline 2ml/kg b.wt /intramuscularly. Another group with 50mg/kg b.wt/ intramuscularly/seven days diclofenac was used for inducing toxicity. In experimental groups rats were administrated with different doses of vitamin E along with diclofenac sodium [200 and 400 IU orally and 50mg/kg b.wt/ intramuscularly/seven days]. Showed that there was a rapid increase in the levels of liver function test in diclofenac treated group, which was significantly decreased after pre-treatment with high dose than low dose of vitamin E. The liver acinus showed Centro acinar necrosis of hepatocytes after 7 days of diclofenac treatment, which was prevented by administration of Vitamin E. Drug-induced liver injury possesses a major clinical problem and has become a leading cause of acute liver failure and transplantation. Overstressed liver compromises its detoxification role which may expose it to a variety of diseases and disorders. Diclofenac sodium is a phenylacetic acid derivative, a widely used nonsteroidal anti-inflammatory drug (NSAID) for the treatment of inflammatory conditions such as osteoarthritis, rheumatoid arthritis, polymyositis, dermatomyositis, dental pain, spondyloarthritis, acute migraine, gout attacks and pain management in gall and renal stones. Although the exact mechanism by with diclofenac injuries liver is not understood, some studies explain the toxicity by affecting cytochrome P 450 leading to the production of active metabolites. Administration of different dose of diclofenac sodium induces severe adverse effects in liver and kidney.