Abstract
Acute and subacute hepatotoxicity induced by barakol was investigated in mice. Blood clinical biochemistry parameters (serum AST, ALT, total bilirubin, cholesterol, triglyceride and glucose) and histopathological examination were used as criteria for liver injury. Mice were given barakol in a single dose (100, 200, 300 and 400 mg/kg, p.o.) and repeated doses (100, 200 and 300 mg/kg/day, p.o., 28 days) for acute and subacute toxicity studies, respectively. 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 the hydropic swelling of hepatocytes, scattered degree of necrotic cells around central vein spreading to periportal zone and finally apoptotic cell death around centrilobular zone spreading to periportal area. The degree of the severity of barakol induced liver injury was dose and time dependent. The mechanism involved may be the induction of 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 liver cell damage and its repair. There were signs of liver regeneration and recovery in all doses of barakol treatment. Reduction of total cytochrome P450 content with unchanged protein expression of CYP 3A1 and 2E1, inhibition of mitochondrial respiration and hemolysis of red blood cells may be involved in barakol induced hepatotoxicity.
