Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats

AIM: To study the effect of leflunomide on CCl4-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by subcutaneous injection with 50% CCl4 in Sprague-Dawley rats. The amount of CCl4 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-beta1 (TGF-beta1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-kappaB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks of CCl4 treatment were stained with hematoxylin and eosin. RESULTS: Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-kappaB expression in liver tissue, and reduced elevated serum TGF-kappa1 and NO levels in rats of hepatic fibrosis. CONCLUSION: Leflunomide showed inhibitory action on hepatic fibrosis induced by CCl4 in rats.