IMR Press / FBL / Volume 13 / Issue 18 / DOI: 10.2741/3193

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Inhibiting dipeptidyl peptidase activity partially ameliorates colitis in mice
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1 School of Biological Sciences, Flinders University, Adelaide, South Australia, Australia
2 Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women’s Health Service, Adelaide, South Australia, Australia
3 Discipline of Agricultural and Animal Science, School of Agriculture, Food and Wine, The University of Adelaide, South Australia, Australia
4 Probiodrug AG, Halle, Germany
Academic Editors:Jonathan S. Duke-Cohan, Aleksi Sedo
Front. Biosci. (Landmark Ed) 2008, 13(18), 6850–6858; https://doi.org/10.2741/3193
Published: 1 May 2008
(This article belongs to the Special Issue Dipeptidyl peptidase IV and related molecules in health and disease)
Abstract

New treatment strategies are required for the debilitating inflammatory bowel diseases (IBD), Crohn's Disease and Ulcerative Colitis. DP inhibitors can prolong the bioactivity of the potent intestinotrophic growth factor glucagon-like peptide-2 (GLP-21-33). We investigated whether novel inhibitors of DP activity could modify the course of disease activity in the dextran sulfate sodium (DSS) model of colitis. C57BL/6 mice consumed 2% DSS in drinking water for 6 days. Mice were orally gavaged twice daily with 0.9% saline, 10 mg/kg isoleucyl-cyano-pyrrolidine (P59/99) or isoleucyl-thiazolidine (P32/98). Assessment of disease severity incorporated a disease activity index (DAI), together with histological assessment of crypt area and depth in the distal colon. DP activity was significantly inhibited at all time points. The DAI was significantly lower in the P59/99 and P32/98 treatment groups compared to saline treatment in all three time courses. Crypt hyperplasia (p<0.05) was observed in the saline group compared to P32/98 treatment at day 9. This preliminary study shows that novel inhibitors of DP activity may provide a new treatment strategy for IBD.

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