Effects of a COX-2 preferential agent nimesulide on TNBS-induced acute inflammation in the gut

• Published in: Inflammation 2001-10, Vol.25 (5), p.301-310
• Main Authors: Kankuri, E, Vaali, K, Korpela, R, Paakkari, I, Vapaatalo, H, Moilanen, E
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; aspirin; Aspirin - administration & dosage; Aspirin - pharmacology; Colitis - drug therapy; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacology; Dinoprostone - blood; Dinoprostone - metabolism; Disease Models, Animal; Drug Evaluation, Preclinical; indomethacin; Indomethacin - administration & dosage; Indomethacin - pharmacology; Inflammation - drug therapy; Inflammation - pathology; Inflammatory Bowel Diseases - drug therapy; Isoenzymes - antagonists & inhibitors; Male; nimesulide; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Sulfonamides - administration & dosage; Sulfonamides - pharmacology; Trinitrobenzenesulfonic Acid
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1023/a:1012860509440

In inflammatory bowel disease, increased production of prostaglandins by cyclooxygenase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema, and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in gut inflammation. We compared the effects of nimesulide, a preferential COX-2 inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX-2 expression in the gut and increased circulating concentrations of PGE2 metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg), or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not have a significant effect on any of these measures of inflammation. None of the studied drugs reduced the size of inflammatory mucosal lesions in the colon. In TNBS-induced acute inflammation of the colon, nimesulide reduced the formation of inflammatory edema, probably by a mechanism related to inhibition of PGE2 production by COX-2 pathway. In addition, nimesulide inhibited neutrophil infiltration into inflamed mucosa mimicking the action of dexamethasone.