Effects of a COX-2 preferential agent nimesulide on TNBS-induced acute inflammation in the gut.
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.
Kankuri
E
E
Institute of Biomedicine, Pharmacology, University of Helsinki, Biomedicum, Finland.
Vaali
K
K
Korpela
R
R
Paakkari
I
I
Vapaatalo
H
H
Moilanen
E
E
D000208:Acute Disease; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D003092:Colitis / Q000188:drug therapy; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin; C012655:nimesulide; D007213:Indomethacin