Effects of colchicine and colchiceine in a biochemical model of liver injury and fibrosis.

Abstract

BACKGROUND: The accumulation of collagen is a salient feature of chronic liver injury. The objective of this study was to investigate and compare the therapeutic effectiveness of colchicine and one of its metabolites, colchiceine, to protect rats from developing liver injury and fibrosis. METHODS: To accomplish this, the authors used a procedure developed by others to produce liver injury and fibrosis by chronic administration of CCl4 in rats. The effect of both compounds on collagen metabolism and liver injury was analyzed. RESULTS: Although both compounds prevented increase in collagen synthesis, animals treated with colchicine did not show a reduction in collagen content compared with animals treated with CCl4. On the other hand, the animals treated with colchiceine along with CCl4 showed a 50% reduction in hepatic collagen content as well as an improvement in histological architecture. Both compounds, colchicine and colchiceine, increased the intracellular degradation of collagen in addition to increasing collagenase activity as compared to non-treated rats. However, collagenase activity was lower in animals treated with colchicine and colchiceine than in the fibrotic livers treated with CCl4. The changes in collagen metabolism correlated with changes in parameters of liver injury. CONCLUSIONS: In conclusion, the compound colchiceine may be recommended in the treatment of chronic liver diseases rather than its precursor, colchicine, due to the fact that it showed a lower accumulation of collagen content and has a better anti-fibrogenic effect than does colchicine.