CPI-1189 Protects Against Dextran Sulfate Sodium-induced Colitis in Mice
Beverley Greenwood-Van Meerveld and Karl R. Tyler
DOI : 10.3844/ajptsp.2006.54.59
American Journal of Pharmacology and Toxicology
Volume 1, Issue 3
Nitrone-related therapeutics (NRTs) represent a new class of small molecules potentially effective in the treatment of inflammatory bowel disease (IBD) by protecting cells from damage caused by excess inflammation and/or oxidative stress. The goal of this study was to determine the efficacy and potency of CPI-1189, a novel therapeutic agent, in dextran sulfate sodium (DSS)-induced colitis in mice. Mice received oral doses of either CPI-1189 (3, 10, or 30 mg kg?1) or the methyl cellulose vehicle along with 3% dextran sulfate in their drinking water. Assessment of colitis was by calculation of a disease activity index (DAI) and by histological observations. Signs of colitis in vehicle-treated mice were evident by day 3 using the DAI and with histological confirmation on day 7. In mice given CPI-1189, there was a significant and dose-dependent improvement in all signs of colitis with an overall protection of approximately 50%. These observations suggest that CPI-1189 is a novel, orally active, therapeutic agent that could be developed for the treatment of crohn’s disease and ulcerative colitis in humans.
© 2006 Beverley Greenwood-Van Meerveld and Karl R. Tyler. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.