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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.
AuthorsPatricia Martínez-Moya, Isabel Romero-Calvo, Pilar Requena, Cristina Hernández-Chirlaque, Carlos J Aranda, Raquel González, Antonio Zarzuelo, María Dolores Suárez, Olga Martínez-Augustin, José Juan G Marín, Fermín Sánchez de Medina
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 15 Issue 2 Pg. 372-80 (Feb 2013) ISSN: 1878-1705 [Electronic] Netherlands
PMID23246254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Ursodeoxycholic Acid
  • Trinitrobenzenesulfonic Acid
  • Alkaline Phosphatase
Topics
  • Administration, Oral
  • Alkaline Phosphatase (metabolism)
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects)
  • Colitis, Ulcerative (chemically induced, drug therapy)
  • Crohn Disease (chemically induced, drug therapy)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Intestinal Mucosa (drug effects, immunology)
  • Rats
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid (administration & dosage)
  • Ursodeoxycholic Acid (administration & dosage, adverse effects)

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