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Pharmacology & toxicology

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


PMID 8936557

Abstract

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 micrograms/rat/day, orally. Liver plasma membranes were isolated for high affinity Ca(2+)-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 Ca(2+)-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase plasma membrane and serum enzyme activities as well as the hepatic glycogen content.