Table of Contents
ISRN Inflammation
Volume 2012, Article ID 898153, 8 pages
http://dx.doi.org/10.5402/2012/898153
Research Article

Anti-Inflammatory Effects of Urocanic Acid Derivatives in Models Ex Vivo and In Vivo of Inflammatory Bowel Disease

1Department of Dermatology, Academic Medical Center (AMC), University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
2Tytgat Institute for Liver and Intestinal Research, Academic Medical Center (AMC), University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
3Pathology Department, Academic Medical Center (AMC), University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands

Received 20 June 2012; Accepted 30 July 2012

Academic Editors: L. J. Hofseth and F. Klebl

Copyright © 2012 Arthur Kammeyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Urocanic acid (UCA) derivatives were tested for their anti-inflammatory activity in inflammatory bowel disease (IBD) in two models: ex vivo and an experimental mouse model. Ex vivo: inflamed colonic tissue was incubated in culture medium with or without the UCA derivatives. Biopsies, incubated with UCA derivatives, produced lower levels of proinflammatory cytokines IL-6 and IL-8 as compared to control biopsies. The same compounds also showed increased levels of IL-10, providing an additional indication for anti-inflammatory properties. In vivo: a combination of two imidazoles and a combination of two of their ethyl esters were administered to mice while colitis was induced by oral administration of dextran sodium sulfate (DSS). Some parameters did not show conclusive effects, but the imidazoles and their ethyl esters reduced the area of inflammation and the number of infiltrating neutrophils. Fibrosis and the sum of all histological aspects were reduced by the imidazoles, whereas the ethyl esters reduced the colon weight to length ratio. These results suggest that the UCA derivatives have anti-inflammatory effect on IBD. In addition, fine tuning of the ex vivo model may provide an elegant way to predict anti-inflammatory effects of potential drugs in humans, which may decrease the need for animal experiments.