Efficacy of the inflammatory cell infiltration inhibitor IS-741 on colitis induced by dextran sulfate sodium in the rat.

Abstract

We examined the therapeutic effects of the inflammatory cell infiltration inhibitor IS-741 (N-(2-((ethylsulfonyl)amino)-5-(trifluoromethyl)-3-pyridinyl)-cyclohexanecarboxamide monosodium salt monohydrate) on a rat colitis model. As a result of its effects on leukocyte infiltration, IS-741 inhibits cell adhesion, alleviates symptoms and signs of pancreatitis and multiple organ failure and demonstrates a life-saving effect in a model of severe acute pancreatitis. A rat model was prepared by inducing colitis with 3% dextran sodium sulfate (DSS) and maintaining pathology with 1% DSS. Repeated oral administration of IS-741 at 1, 10 or 100 mg/kg per day was conducted for 2 weeks (during treatment with 1% DSS). IS-741 at each dose decreased the area of erosion in the large intestine, thickening of the wall of the large intestine and anemia caused by melena. Some effects of IS-741 were nearly equivalent to those of the control compound salazosulfapyridine. Furthermore, IS-741 markedly alleviated inflammatory cell infiltration into the intestinal wall. IS-741 improved lesions in a rat DSS model by inhibiting leukocyte infiltration, suggesting the possibility of clinical application of this drug for IBD.

• Authors: S Yotsuya, H Shikama, M Imamura
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 87 Issue 2 Pg. 151-7 (Oct 2001) ISSN: 0021-5198 [Print] Japan
• PMID: 11700014 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Enzyme Inhibitors
• Pyridines
• IS 741
• Sulfasalazine
• Dextran Sulfate

Topics

• Administration, Oral
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Blood Cell Count
• Colitis, Ulcerative (blood, chemically induced, pathology)
• Dextran Sulfate
• Enzyme Inhibitors (therapeutic use)
• Intestinal Mucosa (drug effects, pathology)
• Intestine, Large (drug effects, pathology)
• Male
• Neutrophil Infiltration (drug effects)
• Pyridines (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sulfasalazine (pharmacology)