title: Trimethylcolchicinic acid decreases liver fibrosis and cholestasis induced by prolonged biliary obstruction in the rat.
abstract: 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.
authors.affiliation: Centro de Investigación y de Estudios Avanzados del IPN, Departmento de Farmacología y Toxicología, Mexico, D.F., México.
authors.forename: P
authors.initials: P
authors.lastname: Muriel
authors.forename: P U
authors.initials: PU
authors.lastname: Ostoa-Saloma
authors.forename: J A
authors.initials: JA
authors.lastname: Reyes-Esparsa
authors.forename: L
authors.initials: L
authors.lastname: Rodríguez-Fragoso
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000188:drug therapy*; D003078:Colchicine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D006909:Hydroxyproline / Q000032:analysis; D008026:Ligation; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010960:Plasminogen Activators / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: C009838:trimethylcolchicinic acid; D003094:Collagen; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D010960:Plasminogen Activators; D001663:Bilirubin; D006909:Hydroxyproline; D003078:Colchicine