CPI-1189 Protects Against Dextran Sulfate Sodium-induced Colitis in Mice

Abstract

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 kgˉ1) 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.