Hepatoprotective effect of phyllanthus amarus schum. Et. Thonn. Extract in ethanol treted rats

Abstract

Alcohol (ethanol) induced hepatotoxicity is one major cause of health problem worldwide. Herbs may be useful as an alternative prevetion and treatment in alcohol induced liver diseases. The present study was undertaken to investigate the hepatoprotective effect and its possible mechanism of aqueous extract from Phyllanthus amarus Schum. et. Thonn. (PA) in ethanol induced hepatotoxic rats. In acute toxicity study, rats received single oral dose of PA (25, 50 and 75 mg/kg), 24 hours before single oral dose of ethanol (5 g/kg). In sub-acute toxicity study, rats received ethanol (4 g/kg/day) orally for 21 days. PA at the most effective dose from acute toxicity study was given orally to rats for 7 days after administration of ethanol. Silymarin (5 mg/kg) was used as the reference hepatoprotective agent in both studies. Hepatoprotective parameters were alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), reduced glutathione (GSH), malondialdehyde (MDA), serum triglyceride (STg), hepatic triglyceride (HTg), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), together with histopathological examination. Single oral dose of Ethanol (5 g/kg) significantly increased ALT and AST levels as compared with control rats. Administration of PA (25 and 50 mg/kg) significantly reduced only AST level, while PA (75 mg/kg) significantly reduced both ALT and AST. All doses of PA had no effect on GSH, MDA, STg, HTg, TNF-alpha and IL-1beta. After 21 days of ethanol (4 g/kg/day) administration, the levels of ALT, AST, MDA, HTg, TNF-alpha and IL-1beta were significantly increased. Treatment with PA (75 mg/kg/day) as well as SL (5 mg/kg/day) for 7 days after ethanol offered significant hepatoprotective effect by reducing ALT, AST, MDA, HTg and TNF-alpha levels back to normal. Administration of PA at 75 mg/kg/day alone for 7 days caused no changes in rats. Histopathological observations were also in correlation with the clinical chemistry parameters by showing reversible regeneration of hepatocytes with mitotic figure and normal liver cell morphology. In conclusions, PA (75 mg/kg) given before or after ethanol administration showed a significant hepatoprotective effect in ethanol treated rats. The possible hepatoprotective mechanism of PA may involve membranes membranes stabilization, antioxidant activity, inhibition of fatty liver formation and TNF-alpha production and enhancement of liver regeneration. PA by itself caused no toxic effect assessed by parameters used