Anti-fibrotic effect of malotilate on liver fibrosis induced by carbon tetrachloride in rats.

The effect of malotilate on liver fibrosis of rat induced by carbon tetrachloride (CCl4) was studied. CCl4 was given subcutaneously (1.5 ml/kg) to male Wistar rats twice a week for 11 weeks. Administration of malotilate (100 mg/kg) 5 times a week was started in the 5th experimental week and continued thereafter. The biochemical parameters in serum such as concentration of total protein and transaminase activities were improved by malotilate administration. The livers treated with CCl4 only were atrophic and markedly nodular, and histologically, severe collagen deposition and pseudolobular formation were observed. However, the livers treated with CCl4 and malotilate showed only slight accumulation of collagen fibers although hypertrophic and fatty metamorphosis was observed. Immunocytochemically, type I and type III collagens were stained in livers from rats treated with CCl4 only and rats treated with CCl4 and malotilate, but stainability was rather weak in the latter. The increased amount of hydroxyproline in the liver and that excreted into urine were markedly suppressed by malotilate administration. The levels of protocollagen prolyl hydroxylase activity in the liver were almost the same in CCl4-treated and CCl4 and malotilate-treated rats. However, the levels of collagenolytic enzyme activity were slightly higher in the latter. From these results, anti-fibrotic action of malotilate was clear and involvement of enhanced collagenolytic enzyme activity was suggested.