Comparative Effect of Vitamins on Diclofenac Induced Hepatotoxicity in Rats

Abstract

Drug-induced hepatotoxicity continues to be a main clinical problem that results newlinein acute hepatic failure and transplantation. It is considered to be the most significant newlinereason of the drug-induced hepatotoxic injury. ROS arbitrates increased free radicals that newlinecan directly damage hepatocytes and can resulted in hepatotoxicity. Even though the newlineexact mechanism by means of diclofenac injuries in the liver is not well known, few newlinestudies describe the toxicity by affecting cytochrome P 450, leading to the active newlinemetabolite production. This study was conducted to display hepatic changes following newlinediclofenac treatment and also to investigate the hepatoprotective activities of Vitamin A, newlineE and C in diclofenac administered rats. The diclofenac induction dose was fixed in the newlinefirst phase of the experimental trail. Among the three dosage of diclofenac (25, 50 and newline100 mg/kg.b.wt) the 50mg of diclofenac was selected for the current study to induce newlinehepatotoxicity. Based upon the previous study the therapeutic doses for Vitamin A, C and newlineE was selected and further hepatoprotective studies were carried out. newlineThe general biochemical parameters, serum and liver marker enzymes, hepatic newlineantioxidants, inflammatory biomarkers, PI3 and AKT-308 protein expression and newlinehistopathology studies were carried out to analyze the comparative action of the vitamins newlineA, C and E. The CREB protein expression by immunohistochemistry and liver newlinemetabolizing enzymes levels were also measured to identify its therapeutic mechanism. newlineThe better action was showed by vitamin C compared to vitamin A treatment newlineagainst diclofenac induced hepatic injury. The hepatoprotection by Vitamin E is more newlinewhen compared with the other two vitamins. Hence, it may be advised that vitamin E may be taken as a supplement in patients treated with Diclofenac. newline newline