Efficacy of the inflammatory cell infiltration inhibitor IS-741 on colitis induced by dextran sulfate sodium in the rat.
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.
Yotsuya
S
S
Central Research Institute, Ishihara Sangyo Kaisha, Ltd., Kusatsu, Shiga, Japan. s-yotsuya@iskweb.co.jp
Shikama
H
H
Imamura
M
M
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001772:Blood Cell Count; D003093:Colitis, Ulcerative / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D016264:Dextran Sulfate; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007420:Intestine, Large / Q000187:drug effects / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012460:Sulfasalazine / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D011725:Pyridines; C097462:IS 741; D012460:Sulfasalazine; D016264:Dextran Sulfate