Comparing the effect of statins on hepatic fibrosis induced by carbon tetrachloride in Wistar rats

Abstract

Background: The clinical studies have shown contrary results regarding hepatoprotective effect of statins. However, antifibrotic properties of statins in in vitro and in vivo experimental models have been demonstrated. The purpose of this study was to assess and compare the effect of statins on serum liver enzymes and their antifibrotic effects.Methods: Forty two rats were divided into 7 groups (I to VII) (n=6). Liver toxicity was induced by injecting carbon tetrachloride (1 ml/kg). Control groups received corn oil (0.1 ml/100 gm) and carboxy methyl cellulose (0.50%) respectively. Group III to VII received carbon tetrachloride (CCl4) for 6 weeks and then groups IV, V, VI and VII received simvastatin (10 mg/kg), atorvastatin (15 mg/kg), rosuvastatin (2 mg/kg) and silymarin (50 mg/kg) for another 8 weeks respectively. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels were estimated in all the groups at baseline, 6 weeks and 14 weeks. At 14 weeks, histopathology of liver was done in all groups.Results: At 14 weeks, all the test groups (IV, V and VI) showed a significant decrease in serum ALT, AST and ALP levels as compared to control (p<0.05) and group III (p<0.05). On intergroup comparison, liver enzymes in rats in group VI (rosuvastatin) and group V (atorvastatin) were decreased more in comparison to group IV (simvastatin) but the difference was not statistically significant except for AST levels where the difference was significant between the statins. There was decrease in hepatic fibrosis by statins with rosuvastatin being superior followed by atorvastatin and simvastatin.Conclusions: In the present study statins decreased the serum AST, ALT and ALP levels and histopathological changes were reversed by statins in CCl4 induced hepatotoxic models.