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

Resolution of Liver Fibrosis in Chronic CCl4 Administration in the Rat after Discontinuation of Treatment: Effect of Silymarin, Silibinin, Colchicine and Trimethylcolchicinic Acid

“…This scheme of treatment prompted us to evaluate the ability of silymarin, silibinin, colchicine and trimethylcolchicinic acid to reverse fibrosis previously established by prolonged chronic CCl 4 administration. Interestingly, despite that we have proved previously the ability of these compounds to prevent fibrosis (Mourelle et al 1989; Muriel & Mourelle 1990; Castro & Muriel 1996; Cedillo et al 1996; Muriel 1997; Muriel et al 1997), they failed to reverse it significantly when compared with an appropriate vehicle control.…”

“…The scheme of treatment presented herein may be an excellent tool to study the ability of drugs to reverse fibrosis. In this model of fibrosis, colchicine, TMCA, silymarin or silibinin treatment showed no significant fibrolitic effect despite its well known antifibrogenic properties (Mourelle et al 1989; Muriel & Mourelle 1990; Castro & Muriel 1996; Cedillo et al 1996; Muriel 1997; Muriel et al 1997).…”

Fibrosis and glycogen stores depletion induced by prolonged biliary obstruction in the rat are ameliorated by metadoxine

“…Thus, it seemed reasonable to administer 120 mg/kg of body weight divided into two doses of 60 mg/kg/i.p. Previously we have studied the effect of colchicine at various doses on prolonged bile duct obstruction in the rat (19). We found that the administration of colchicine 10 μg/rat/day for 2 months produced no diarrhea, but 50 μg/rat/day produced diarrhea in all animals treated.…”

“…Colchicine at a dose of 200 μg/rat/day produced, in addition to severe diarrhea, a 40% mortality after 2 months of treatment. Thus, in that work (19) and in others (10), including the present one, we have chosen a dose of 10 μg/rat/day.…”

“…Several studies have shown that the production of proinflammatory cytokines, particularly TNF‐α, increases in conjunction with liver damage produced by ischemia–reperfusion, endotoxin or hepatotoxicants. Neutralization or suppression of TNF‐α decreases the extent of hepatic injury induced by chronic BDL (19), acetaminophen (22), acute CCl 4 intoxication (23), ischemia–reperfusion (24) and cadmium‐induced hepatotoxicity (25), among others.…”