SILYMARIN AMELIORATES LIVER DAMAGE BY MODULATING OXIDATIVE STRESS AND APOPTOSIS IN LIVER OF STREPTOZOTOCIN-INDUCED DIABETIC RATS.

Objective:- Hepatic injury and cell death in diabetes is a major health problem worldwide. Oxidative stress is a contributing factor in diabetic complications including liver. Various preclinical and clinicalreports have indicated the antidiabetic effect of silymarin (SMN). The objective of this study was to investigate the effect of SMN on oxidative stress and apoptosis in liver of streptozotocin (STZ)-induced diabetes in rats. Methods- :Streptozotocin (STZ, 50 mg/kg, ip) was injected into male rats, and after diabetic induction SMN (80mg/kg) was orally administered for 21 days. Results:- STZ produced remarkable hyperglycemia and a decrease in insulin level. This is accompanied by increased alkaline phosphatase activity and bilirubin level with remarkable decrease in albumin content in serum of diabetic rats. A significant increase in oxidative stress was demonstrated by increased lipid peroxidation with a decrease in the glutathione levels in liver of diabetic rats. Increased percentages of apoptosis with down-regulation of Bcl-2 and activation of Bax as well as the caspases-3 and 9 were demonstrated in the diabetic rats. SMN-treated rats showed significantly lower levels of blood glucose,bilirubin and alkaline phosphatase,and higher levels of insulin and albumin when compared with diabetic group.SMN also prevented the increase in MDA and stimulated the GSH production in liver of STZ-treated rats indicating improved hepatic redox state. SMN-treated rats showed significantly higher level of Bcl-2 and lower expression levels ofBax and the caspases-3 and 9 when compared with diabetic rats. These effects might contribute and lead to control apoptosis in the liver of diabetic condition. Conclusion:- SMN has an ability to protect liver by modulating redox stateand apoptosis.These data indicate that SMN may be useful as a therapeutic agent for liver injury in type 1 diabetes.