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

Department of Pharmacology, Basic Medical School, Wuhan University, Wuhan 430071, Hubei Province, China.
Pharmacological Research (Impact Factor: 4.41). 05/2007; 55(4):280-6. DOI: 10.1016/j.phrs.2006.12.003
Source: PubMed


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 (CCl(4)), 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 alpha-smooth muscle actin (alpha-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 alpha-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.

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    • "Thus, the exact role of L-type voltageoperated calcium channels in HSCs stimulated by TGF-b1 remains to be elucidated. Verapamil was reported to suppress liver fibrosis induced by multiple hepatotoxic factors, including CCl 4, ethanol and high cholesterol, in rats (Xu et al., 2007). However, doses of 20, 40 and 80 mg·kg -1 ·day -1 were suggested to be inappropriately high doses for the following reasons. "
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