Lack of beneficial effect of COX-2 inhibitors in an experimental model of colitis.
Expression of the COX-2 enzyme has been reported in animal models of inflammatory bowel disease (IBD) as well as in patients affected by ulcerative colitis and Crohn's disease. Recently, selective inhibitors of COX-2 have become available. In this study we have evaluated three highly selective COX-2 inhibitors, NS-398, SC-58125 and PD-138387, on the trinitro-benzene sulfonic acid (TNBS) model of colitis in rats. Daily oral administration of the three compounds evaluated up to a dose of 100 mg/kg failed to significantly modify any of the parameters evaluated. Our data show that despite their potent extraintestinal antiinflammatory activity, COX-2 inhibitors do not seem to have any beneficial effect in TNBS colitis and raise the question whether this therapeutic approach would be beneficial in patients with IBD.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D007527:Isoenzymes / Q000187:drug effects*; D008297:Male; D009578:Nitrobenzenes / Q000627:therapeutic use; D009195:Peroxidase / Q000037:antagonists & inhibitors; D010544:Peroxidases / Q000187:drug effects*; D010636:Phenols / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid