Dose-dependent protective effects of silymarin against ccu-induced liver damage in rats

ABSTRACT

Silymarin, the dried extract of the ripe seeds of Silybum marianum is found to be a powerful protective agent against xenobiotics-induced tissue injury in many organs, including liver. However, the dose-dependent relationship of this effect and tissue availability is not fully explored. So, this project was designed to evaluate the relationship between dose, tissue availability and tissue protection of silymarin against ccu-induced hepatic toxicity in rats. The tissue protective effects of silymarin were studied through the pre-treatment of rats with various doses [250, 500, and l000 mg/kg] orally twice daily before the induction of hepatotoxicity of ccl4. Malondialdehyde [MDA] and glutathione [GSH] were evaluated in the serum and tissue homogenate. The activities of different enzymes, which are considered as indicators of organ toxicity like alanine amino transaminase [ALT] and aspartate aminotransaminase [AST] were assessed. Histopathological examination of stained tissue sections from the liver were done to evaluate the protective effect at the microscopical levels. In addition, silymarin level in liver tissue homogenate -was evaluated using HPLC method. The data obtained indicated that, a significant amelioration of oxidative stress experimentally induced in the liver of rats was produced by silymarin, as evidenced by lowering MDA contents and elevation of GSH levels both in the tissues and serum compared with controls. Serum activities of ALT and AST were normalized. Additionally, histologically evident damage in the liver had improved In addition, increasing silymarin dose after oral administration resulted in increased tissue availability of many constituents. There is a dose-dependent relationship in the hepatoprotective effect of silymarin against ccU-induced hepatotoxicity in rats