The Efficacy of Antioxidative Therapy in Hepatic Fibrosis Induced Experimentally by Bile Duct Ligation in Rats

Liver fibrosis which is a common result of chronic hepatic injury of diverse origins might be related to the occurrence of oxidative stress and accumulation of free radicals. It is characterized essentially by increased secretion and accumulation of different components Extracellular Matrix proteins (ECM). To investigate the beneficial effect of combined supplementation of vitamin E and selenium on hepatic fibrosis induced experimentally in bile duct-ligated rats. Forty albino rats were randomly assigned to 4 groups (10 rats in each); control group, sham-operated group Bile Duct-Ligated (BDL) group where the bile ducts of rats were ligated and BDL group co-treated with vitamin E and selenium where the rats underwent bile duct ligation and were fed with chow supplemented with vitamin E (250 mg kg(-1)) and selenium (0.2 mg kg(-1) diet) starting from three days before the operation. At the end of 3rd week, the rats were sacrificed where blood was taken for biochemical estimations of serum enzymes and bilirubin. Fresh liver tissue was taken for determination of hydroxyproline content. Also, other liver samples of 5 mm(3) were immediately fixed and processed for immunohistochemical demonstration of collagen type I and IV, fibronectin and laminin using the indirect immunoperoxidase method. Bile duct ligation resulted in a marked elevation in the levels of serum enzymes, bilirubin and hydroxyproline together with extensive bile duct proliferation. Strong staining was found for collagens I and IV, fibronectin and laminin in enlarged portal spaces around the newly formed bile ductuless. Co-treatment with vitamin E and selenium resulted in a shift in the serum enzymes, bilirubin and hydroxyproline towards the normal values. Also, a remarkable decrease of bile duct proliferation and in the intensity of staining for different ECM components in the portal spaces was observed. Antioxidants vitamins E and selenium combination attenuate the development of hepatic fibrosis in bile duct-ligated rats. Long-term, prospective studies in humans with chronic cholestatic liver diseases may be helpful to evaluate the beneficial effects of these elements.