Comparative study of colchicine and trimethylcolchicinic acid on prolonged bile duct obstruction in the rat.

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.