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

“…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).…”

“…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.…”

Effect of Colchicine and Trimethylcolchicinic Acid on CCl4‐Induced Cirrhosis in the Rat

“…1987). However, neither trimethylcolchicinic acid nor colchicine could prevent the increase in malondialdehyde levels showing that these compounds are not acting by inhibiting lipid peroxidation processes, but that other citoprotective (Muriel et al 1993;Mourelle & Meza 1989;Castro & Muriel 1996) or antifibrotic effects should be considered. In fact, we have observed that trimethylcolchicinic acid reverses fibrosis induced by cholestasis probably by a plasminogen activatorrelated mechanism (unpublished observations).…”

“…Unfortunately, colchicine side effects (Wallace et al 1970;Hoang et al 1982;Merchant & Singh 1973;Stein & Stein 1973) do not allow it to be administered at higher doses than 1 mg per patient per day. It has been reported that trimethylcolchicinic acid, a colchicinoid that does not bind to microtubule protein (Zweig & Chignell 1973), is less toxic than colchicine (Castro & Muriel 1996). Therefore the possibility of increasing trimethylcolchicinic acid doses should be considered to obtain a better pharmacological effect without the common side effects attributed to colchicine's ability to inhibit microtubule assembly (Kershenobich et al 1979(Kershenobich et al & 1988Bodenheimer et al 1988;Warnes et al 1987;Kaplan 1989).…”

“…1) does not bind tubulin (Zweig & Chignell 1973). Previously, we have observed that trimethylcolchicinic acid can prevent cholestasis in the rat (Castro & Muriel 1996).…”