title: Effects of nimesulide, a preferential cyclooxygenase-2 inhibitor, on carrageenan-induced pleurisy and stress-induced gastric lesions in rats.
abstract: Intrapleural injection of carrageenan in rats increased prostaglandin E2 (PGE2) production and induced newly synthesized cyclooxygenase-2 (COX-2) in pleural exudate cells without affecting COX-1 levels. Nimesulide, a preferential inhibitor of COX-2, reduced pleural PGE2 production and was almost as active as indomethacin and 10 times more active than ibuprofen. Only COX-1, and nc COX-2, was detected in gastric mucosal cells, and PGE2 concentration of gastric mucosa was significantly decreased by indomethacin and ibuprofen. The decrease in gastric PGE2 production induced by indomethacin and ibuprofen was enhanced in stressed rats, resulting in aggravation of stress-induced gastric lesions at anti-inflammatory doses. However, nimesulide did not produce stress-induced gastric lesions even at 30 times the anti-inflammatory dose. This supports the hypothesis that inhibition of COX-1 causes unwanted side effects and inhibition of COX-2 produces anti-inflammatory effects.
authors.affiliation: Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakatsugi
authors.forename: N
authors.initials: N
authors.lastname: Terada
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Horie
authors.forename: M
authors.initials: M
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D005079:Excipients / Q000494:pharmacology; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005756:Gastritis / Q000139:chemically induced* / Q000378:metabolism; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D010998:Pleurisy / Q000139:chemically induced; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005079:Excipients; D007527:Isoenzymes; D008565:Membrane Proteins; D013449:Sulfonamides; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; C012655:nimesulide; D007052:Ibuprofen; D007213:Indomethacin