Research Article Open Access

CPI-1189 Protects against TNBS-induced Colitis in a Rodent Model

Beverley Greenwood-Van Meerveld1 and Karl Tyler1
  • 1 University of Oklahoma Health Sciences Center, United States

Abstract

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.

American Journal of Pharmacology and Toxicology
Volume 2 No. 2, 2007, 30-38

DOI: https://doi.org/10.3844/ajptsp.2007.30.38

Submitted On: 4 December 2006 Published On: 30 June 2007

How to Cite: Meerveld, B. G. & Tyler, K. (2007). CPI-1189 Protects against TNBS-induced Colitis in a Rodent Model. American Journal of Pharmacology and Toxicology, 2(2), 30-38. https://doi.org/10.3844/ajptsp.2007.30.38

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Keywords

  • Inflammatory bowel disease
  • trinitrobenzene sulfonic acid
  • colon
  • rat