Abstract
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.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Colitis / chemically induced
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Colitis / drug therapy*
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Colitis / enzymology
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / therapeutic use*
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Dinoprostone / antagonists & inhibitors
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Isoenzymes / drug effects*
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Male
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Nitrobenzenes / therapeutic use
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Peroxidase / antagonists & inhibitors
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Peroxidases / drug effects*
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Phenols / therapeutic use
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Prostaglandin-Endoperoxide Synthases / drug effects*
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Pyrazoles / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Sulfonamides / therapeutic use
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Thiazoles / therapeutic use
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Trinitrobenzenesulfonic Acid
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Nitrobenzenes
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PD 138387
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Phenols
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Pyrazoles
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Sulfonamides
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Thiazoles
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
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Trinitrobenzenesulfonic Acid
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Peroxidases
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Peroxidase
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone