title: Comparative study of colchicine and trimethylcolchicinic acid on prolonged bile duct obstruction in the rat.
abstract: The aim of this work was to compare the effects of colchicine and trimethylcolchicinic acid (TMCA) on liver damage induced by bile duct ligation (BDL) for 2 months in male Wistar rats. Colchicine was evaluated at a dose of 10 micrograms rat-1 day-1, p.o. only, because higher doses produced diarrhoea and death. Trimethylcolchicinic acid showed no toxic effects at 10, 50 or 100 micrograms rat-1 day-1, p.o. Biliary obstruction resulted in a 65% mortality, colchicine decreased it to 46% and TMCA (10 micrograms) to 33.3%. Serum markers of liver damage increased by BDL (P < 0.05), colchicine prevented it partially (P < 0.05) and TMCA did it in a dose-dependent manner. Liver peroxidation increased 10 times by BDL and both drugs prevented it. Hepatic glycogen content decreased 80% by BDL, colchicine TMCA (10 micrograms) failed to preserve it and 50 micrograms of TMCA preserved it completely. Hepatocyte and erythrocyte plasma membrane Na+/K(+)- and Ca(2+)-ATPase activities decreased after BDL (P < 0.05) and 100 micrograms of TMCA preserved normal ATPase activities. It is concluded that TMCA is better than colchicine for protecting the liver from BDL-induced cirrhosis and, due to its lower toxicity, can be used at higher and more effective doses without the common side-effects of colchicine, thus making TMCA a suitable compound to be studied in other hepatic lesions and in humans.
authors.affiliation: Escuela Superior de Medicina, IPN, Mexico, D.F.
authors.forename: V
authors.initials: V
authors.lastname: Castro
authors.forename: P
authors.initials: P
authors.lastname: Muriel
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003078:Colchicine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: C009838:trimethylcolchicinic acid; D003078:Colchicine