Comparative Study of Colchicine and Trimethylcolchicinic Acid on Prolonged Bile Duct Obstruction in the Rat

✍ Scribed by Virginia Castro; Pablo Muriel

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 777 KB
• Volume: 16
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/(sici)1099-1263(199605)16:3<269::aid-jat346>3.0.co;2-y

✦ Synopsis

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 pg rat-' day-', p.0. only, because higher doses produced diarrhoea and death. Trimethylcolchicinic acid showed no toxic effects at 10, 50 or 100 pg rat-' day-', p.0. Biliary obstruction resulted in a 65% mortality, colchicine decreased it to 46% and TMCA (10 pg) 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 and TMCA (10 pg) failed to preserve it and 50 pg of TMCA preserved it completely. Hepatocyte and erythrocyte plasma membrane Na+/K+-and Ca2+-ATPase activities decreased after BDL (P < 0.05) and 100 pg 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. COLCHlClNE TRI METHYLCOLCHICINIC ACID Figure 1. Chemical structures of colchicine and trimethylcolchicinic acid.