Protective effect of verapamil on multiple hepatotoxic factors-induced liver fibrosis in rats

The purpose of the present work was to investigate the effect of verapamil on liver fibrosis induced by multiple hepatotoxic factors in rats. Male Wistar rats were divided into a normal control group, a liver fibrosis model control group, and verapamil groups with different dosages. Multiple hepatotoxic factors including carbon tetrachloride (CCI4), ethanol and high cholesterol were used to make the animal model of liver fibrosis. The parameters of serum L-alanine aminotransferase (ALT), liver malondialdehyde and hydroxyproline contents were measured. Samples of the liver obtained by biopsy were subjected to histological and immunohistochemical studies for the expressions of a-smooth muscle actin (cx-SMA) and transforming growth factor-beta(1) (TGF-beta(1)). Results showed that verapamil induced a dose-dependent decrease of serum ALT, liver malondialdehyde and hydroxyproline compared with liver fibrosis model control. Verapamil reduced hepatocyte degeneration and necrosis, and delayed the formation of liver fibrosis. The levels of expression of a-SMA and TGF-beta(1) in the hepatic tissue of three of the verapamil-treated groups were significantly less than those of the liver fibrosis model control group. The results showed that verapamil acts against the formation of liver fibrosis, the mechanism might be due to a protective effect for hepatocytes and through decreasing TGF-beta(1) to block the activation of hepatic stellate cells (HSCs) and collagen gene expression. (C) 2006 Elsevier Ltd. All rights reserved.