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 cir rhosis. However, due to its toxicity, other drugs are being evaluated and colchicine-like molecules may be good alternatives. The aim of thi s work was to compare the beneficial effects of colchicine and trimeth ylcolchicinic acid (a colchicinoid less toxic than colchicine) on CCl4 -cirrhosis. The drugs were administered either through CCl4 administra tion (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 af finity Ca2+-ATPase, gamma-glutamyl transpeptidase and alkaline phospha tase activities. The activities of gamma-glutamyl transpeptidase and a lkaline phosphatase were also measured in serum. Liver glycogen conten t and a marker for lipid peroxidation were determined in liver samples . We found that both compounds preserved and significantly reversed hi gh affinity Ca2+-ATPase, gamma-glutamyl transpeptidase and alkaline ph osphatase plasma membrane and serum enzyme activities as well as the h epatic glycogen content.