The dopamine agonist piribedil exerts hepatoprotective effects on carbon tetrachloride-induced hepatic damage

Abstract

This study aimed to investigate the effect of piribedil, a drug used for the treatment of Parkinson’s disease and which has direct dopaminergic stimulating action, on the acute hepatic injury in mice. Hepatotoxicity was induced by CCl4 orally (0.28 ml/kg). Piribedil at three dose levels (4.5, 9, or 18 mg/kg) or silymarin (25 mg/kg) was given orally daily for 7 days, starting at time of administration of CCl4. Liver damage was assessed by determining liver serum enzyme activities and by hepatic histopathology. Piribedil administration lessened the increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also prevented the development of hepatic necrosis caused by CCl4. The effect of piribedil was dose-dependent one. Piribedil administered at the above doses caused significant reduction in the elevated plasma ALT by −36.3%, −42.8%, and −52.4% and ALP by −25%, −36.9%, and −57.1%, respectively. AST decreased by −36.4% and −46.2% by piribedil at 9 or 18 mg/kg, respectively. In comparison, the elevated serum ALT, AST, and ALP levels decreased to −69.6%, −64.2%, and −68.5% of control values, respectively, by silymarin. Histopathologic examination of the livers of CCl4-treated mice administered piribedil at 9 mg/kg showed noticeable amelioration of the liver tissue damage, while piribedil at 18 mg/kg resulted in restoration of the normal architecture of the liver tissue as well as noticeable increase in the protein content of hepatocytes. It is concluded that administration of the dopaminergic agonist piribedil in a model of liver injury induced by CCl4 results in amelioration of liver damage.