In vivo effect of cinnarizine on acute hepatic damage in mice

ABSTRACT

This study aimed to investigate the effect of cinnarizine, a drug used for the treatment of motion sickness and which has direct anti-dopaminergic features [Dopamine Dl and D2 receptor blockade], on the acute hepatic injury in mice. Hepatotoxicity was induced by CCI4 orally [0.28 ml/100 g given twice with one week apart]. Cinnarizine at three dose levels [5, 10 or 20 mg/kg] or silymarin [22 mg/kg] were given orally daily for 14 days. starting at the time of administration of CCI4. Liver damage was assessed by determining liver serum enzyme activities and by hepatic histopathology. Cinnarizine decreased the increases in serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP] and also prevented the development of hepatic necrosis caused by CCI4. The effect of cinnarizine was a dose-dependent one. Cinnarizine administered at 10 or 20 mg/kg caused significant reduction in the elevated plasma ALT by 32.7, 34.3%, AST by 18.8, 34.7% and ALP by 32.8, 42.9%, respectively. In comparison, the elevated serum ALT, AST and ALP levels were decreased by 42.1%, 37.9% and 43.4% of controls, respectively by 22 mg/kg of silymarin. Histopathologic examination of the livers of CCI4-treated mice administered cinnarizine at 20 mg/kg showed marked restoration of the normal architecture of the liver tissue with minimal fibrosis. It is concluded that administration of cinnarizine in a model of liver injury induced by CCI4 results in less liver damage