CPI-1189 Protects against TNBS-induced Colitis in a Rodent Model
Beverley Greenwood-Van Meerveld and Karl Tyler
DOI : 10.3844/ajptsp.2007.30.38
American Journal of Pharmacology and Toxicology
Volume 2, 2007
Nitrone-related therapeutics (NRTs) represents a new class of molecules that may be effective in treating inflammatory conditions. The goal of this study was to examine the effect of CPI-1189 in a rat model of inflammatory bowel disease (IBD). Colonic inflammation was induced by an enema of trinitrobenzene sulfonic acid (TNBS). Saline-enema treated rats served as controls. After 3 days colonic damage was assessed morphologically using a validated scoring system and through measurement of myeloperoxidase (MPO), an enzymatic marker of inflammation. We found that a dose-dependent protection from TNBS-induced colonic damage was observed in rats given 10-70 mg kgˉ1 of CPI-1189 treated p.o. 1 hr. before the TNBS enema. Consistent with the 55% absolute oral bioavailability of CPI-1189, greater protection (77%) was seen when CPI-1189 (30 mg kgˉ1) was administered intravenously 1 hr. before the TNBS enema. In a separate series of healing experiments where CPI-1189 was administer after the TNBS inflammatory response had peaked, CPI-1189 at a dose of 90 mg kgˉ1 p.o. reduced the TNBS colitis. CPI-1189 prevents and heals TNBS-induced colonic damage in rats suggesting that CPI-1189 may be a novel agent for the treatment of IBD.
© 2007 Beverley Greenwood-Van Meerveld and Karl 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.