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 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.
Cedillo
A
A
Pharmacology & Toxicology Department, Cinvestav-I.P.N., México, D.F., México.
Mourelle
M
M
Muriel
P
P
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002462:Cell Membrane / Q000201:enzymology; D003078:Colchicine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D008112:Liver Glycogen; C009838:trimethylcolchicinic acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000252:Calcium-Transporting ATPases; D003078:Colchicine