Hepatotoxicity studies of barakol in mice

Abstract

Acute and subacute hepatotoxicity induced by barakol were investigated in mice. Blood clinical biochemistry parameters including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, cholesterol, triglyceride, glucose and histopathological examination were used as indices of liver injury. Barakol in a single dose (100, 200, 300, and 400 mg/kg, po) and repeated doses (100, 200, and 300 mg/kg/day, po, 28 days) were given to mice for acute and subacute toxicity studies. The acute and subacute hepatotoxic findings included the increase in total bilirubin, AST and ALT levels and the decrease in cholesterol, triglyceride and glucose concentrations which corresponded to the histopathological examination showing hydropic degeneration, centrilobular and invaded to periportal necrosis and apoptosis. The degree of severity from barakol-induced liver injury was dose- and time-dependent. The mechanisms involved may be the induction of coagulative necrosis and apoptosis resulting in the disturbance of normal liver cell function. The ultimate outcome of hepatotoxicity by barakol depended on the balance between the extent of damage and repair processes. There were signs of liver regeneration and recovery in all doses of barakol treatment. Reduction of total cytochrome P450 contents with unchanged protein on expression of CYP 3A1 and 2E1, inhibition of mitochondrial respiration and hemolysis of red blood cells may involve in barakol-induced hepatotoxicity