Hepatoprotection by malotilate against carbon tetrachloride-alcohol-induced liver fibrosis

Subchronic treatment of male rats with carbon tetrachloride (CCl4, twice weekly 0.2 ml/kg p.o.) and feeding a 5% alcohol solution instead of drinking water led to a nearly complete liver cirrhosis in all animals within 4 weeks. This was also documented by a three fold increase in hepatic total hydroxyproline content. Steatosis was quantified by enhanced liver triglyceride concentrations and acute necroses by increments of serum enzyme activities (GPT, SDH). Daily oral treatment with malotilate (100 mg/kg) totally prevented the development of liver cirrhosis, hepatic hydroxyproline accumulation and increases in serum enzyme activities induced by CCl4-alcohol. In cianidanol-treated rats (100 mg/kg p.o.) only portoseptal fibrosis was seen, however hydroxyproline and triglyceride accumulation as well as enhanced serum enzyme activities were not suppressed. D-penicillamine (300 mg/kg p.o.) and colchicine (50 micrograms/kg i.p.) failed to protect rats against CCl4-alcohol induced fibrosis, necrosis and steatosis in this model.