Colchicine is effective in decreasing hepatic
fibrosis. However, several toxic reactions have been reported after
colchicine treatment which are attributed to its ability to bind
tubulin. The aim of this work is to determine if
trimethylcolchicinic acid, which does not bind
tubulin, is able to decrease experimental
liver fibrosis and
cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of
trimethylcolchicinic acid (TMCA, 100 micrograms rat-1 day-1, p.o.) began 4 weeks after biliary obstruction and continued for a further 4 weeks. The liver was used for histological and ultrastructural analysis and for
collagen quantification (
hydroxyproline content). The degradation of
Matrigel and
collagen (types I and III), as well as
plasminogen activator activity, was determined in liver homogenates. Bilirubins and
enzyme activities were measured in serum.
Trimethylcolchicinic acid was able to improve normal liver histology, ultrastructure,
collagen content and
biochemical markers of liver damage. It also increased
matrigel degradation and
plasminogen activator activity. The mechanism of TMCA is probably associated with its ability to increase
Matrigel degradation; however, other actions cannot be discarded.