Abstract
Effect of malotilate on chronic liver injury induced by carbon tetrachloride (CCl4) was studied in rats. Rats were intraperitoneally injected with CCl4 dissolved in olive oil at a rate of 0.5 ml/kg, twice a week for 10 weeks. Malotilate mixed with a laboratory chow diet at a concentration of 0.2% was fed to the rats for 10 weeks, the last 5 or 2 weeks in parallel with CCl4-injection. Significant elevations of plasma transaminase activities, increases of liver triglycerides (TG), malonedialdehyde (MA), and 4-hydroxyproline contents, and decrease of liver protein content were observed at 5, 8, and 10 weeks after initiation of CCl4-injection. In the histopathological study, vacuolation at 5 weeks, vacuolation and fibrosis at 8 weeks, and extreme fibrosis at 10 weeks were observed in rat liver with CCl4-injection. In the rats fed the diet containing malotilate for 10 weeks, these changes of biochemical parameters and histopathological findings were not observed at any time and only slight increase of liver TG and slight vacuolation at 10 weeks was observed. When rats were fed the diet containing malotilate for the last 5 or 2 weeks, these changes of biochemical parameters and histopathological findings caused by CCl4 were improved thereafter. Although the covalent bindings of the radioactivity from 14CCl4 to liver and liver microsomal phospholipids were slightly depressed by malotilate feeding, it is difficult to explain the protective effect of malotilate on the liver injury only by this phenomenon. Other probable mechanisms for this effect were discussed.
