Effect of colchicine and trimethylcolchicinic acid on CCl4-induced cirrhosis in the rat

Colchicine is one of the most promising drugs for the treatment of cirrhosis. However, due to its toxicity, other drugs are being evaluated and colchicine-like molecules may be good alternatives. The aim of this work was to compare the beneficial effects of colchicine and trimethylcolchicinic acid (a colchicinoid less toxic than colchicine) on CCl4-cirrhosis. The drugs were administered either through CCl4 administration (8 weeks) or after CCl4 intoxication for 4 weeks at a dose of 10 mu g/rat/day, orally. Liver plasma membranes were isolated for high affinity Ca2+-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase activities. The activities of gamma-glutamyl transpeptidase and alkaline phosphatase were also measured in serum. Liver glycogen content and a marker for lipid peroxidation were determined in liver samples. We found that both compounds preserved and significantly reversed high affinity Ca2+-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase plasma membrane and serum enzyme activities as well as the hepatic glycogen content.