title: Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis.
abstract: The denomination of inflammatory bowel disease comprises a group of chronic inflammatory diseases of the digestive tract, ulcerative colitis and Crohn's disease being the most important conditions. Bile acids may play a role both in etiology and pharmacology of this disease. Thus, although deoxycholic acid is regarded as a proinflammatory agent ursodeoxycholic acid, which is currently being used to treat certain types of cholestasis and primary biliary cirrhosis, because of their choleretic, cytoprotective and immunomodulatory effects, it has been reported to exert an anti-inflammatory activity. We aim to confirm and characterize the intestinal antiinflammatory activity of ursodeoxycholic acid. The experimental model trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats has been used. Animal status was characterized by a number of macroscopic and biochemical parameters. Oral administration of ursodeoxycholic acid was able to ameliorate experimental colonic inflammation. This occurred only at a relatively high dose (50 mg/kg day), whereas ursodeoxycholic acid was without significant effect at doses of 10 and 25 mg/kg day. The therapeutic effect was evidenced, among others, by a higher body weight recovery, a diminished affected to total mucosal area and lower alkaline phosphatase activity in treated vs. control (TNBS treated) animals. These results indicate that, at the appropriate dose, ursodeoxycholic acid is a potentially useful drug to reduce intestinal inflammation and could be envisaged to be incorporated in the treatment of inflammatory bowel diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, University of Granada, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martínez-Moya
authors.forename: Isabel
authors.initials: I
authors.lastname: Romero-Calvo
authors.forename: Pilar
authors.initials: P
authors.lastname: Requena
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández-Chirlaque
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Aranda
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Suárez
authors.forename: Olga
authors.initials: O
authors.lastname: Martínez-Augustin
authors.forename: José Juan G
authors.initials: JJ
authors.lastname: Marín
authors.forename: Fermín Sánchez
authors.initials: FS
authors.lastname: de Medina
mesh_terms: D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D003424:Crohn Disease / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014580:Ursodeoxycholic Acid; D014302:Trinitrobenzenesulfonic Acid; D000469:Alkaline Phosphatase