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 trim ethylcolchicinic acid (TMCA) on liver damage induced by bile duct liga tion (BDL) for 2 months in male Wistar rats, Colchicine was evaluated at a dose of 10 mu g rat(-1) day(-1), p.o. only, because higher doses produced diarrhoea and death, Trimethylcolchicinic acid showed no toxi c effects at 10, 50 or 100 mu g rat(-1) day(-1), p.o. Biliary obstruct ion resulted in a 65% mortality, colchicine decreased it to 46% and TM CA (10 mu g) 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 b y BDL and both drugs prevented it, Hepatic glycogen content decreased 80% by BDL, colchicine and TMCA (10 mu g) failed to preserve it and 50 mu g of TMCA preserved it completely, Hepatocyte and erythrocyte plas ma membrane Na+/K-- and Ca2+-ATPase activities decreased after BDL (P < 0.05) and 100 mu g of TMCA preserved normal ATPase activities, It is concluded that TMCA is better than colchicine for protecting the live r from BDL-induced cirrhosis and, due to its lower toxicity, can be us ed at higher and more effective doses without the common side-effects of colchicine, thus making TMCA a suitable compound to be studied in o ther hepatic lesions and in humans.