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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 no 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.
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References
- Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.Nature New Biology. 1971; 231: 232-235
- Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs.N Engl J Med. 1992; 327: 749-754
- Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing.in: 1st edn. Proc Natl Acad Sci USA. 88. 1991: 2692-2696
- TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue.J Biol Chem. 1991; 266: 12866-12872
- Prostaglandin endoperoxide synthase: regulation of enzyme expression.Biochim Biophys Acta. 1991; 1083: 121-134
- Selective inhibition of inducible cyclooxygenase-2 in vivo is antiinflammatory and nonulcerogenic.in: 1st edn. Proc Natl Acad Sci USA. 91. 1994: 3228-3232
- Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain.in: 1st edn. Proc Natl Acad Sci USA. 91. 1994: 12013-12017
- cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase.in: 1st edn. Proc Natl Acad Sci USA. 89. 1992: 4888-4892
- Selective inhibition of cyclooxygenase 2.Biochem Pharmacol. 1994; 48: 1605-1610
- NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro.Prostaglandins. 1994; 47: 55-59
- Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase.Biochem J. 1995; 305: 479-484
- Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase.in: 1st edn. Proc Natl Acad Sci USA. 90. 1993: 11693-11697
- New insights into the mode of action of anti-inflammatory drugs.Inflammation Res. 1995; 44: 1-10
- The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound.Drug Expl Clin Res. 1989; 15: 501-509
- Mechanism of action of novel anti-inflammatory drugs diflumidone and R-805.Biochem Pharmacol. 1977; 26: 307-311
- Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4′-1-benzopyran-4-one.Arzneim Forsch. 1992; 42: 935-944
- Pre-clinical pharmacological studies with nimesulide.Drugs Exp Clin Res. 1984; 10: 587-597
- Effect of nimesulide on cyclo-oxygenase activity in rat gastric mucosa and inflammatory exudate.Med Sci Res. 1989; 17: 745-746
- NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions.Gen Pharmacol. 1993; 24: 105-110
- Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system.Biochim Biophys Acta. 1994; 1209: 130-139
- Selective inhibition by nimesulide, a novel non-steroidal anti-inflammatory drug, with prostaglandin endoperoxide synthase-2 activity in-vitro.Pharm Sci. 1995; 1: 173-175
- Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs.J Biol Chem. 1993; 268: 6610-6614
- Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs.J Pharmacol Exp Ther. 1994; 271: 927-934
- Effects of indomethacin, tiaprofenic acid and diclofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2.Prostaglandins. 1985; 30: 609-618
- Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica.Prostaglandins. 1980; 20: 947-957
- Detection of inducible prostaglandin H synthase-2 in cells in the exudate of rat carrageenin-induced pleurisy.Biomed Res. 1994; 15: 127-130
- An analysis of the gastro-intestinal side-effects of non-steroidal anti-inflammatory drugs, with particular reference to comparative studies in man and laboratory species.Rheumatol Int. 1982; 2: 1-10
- Is peptic ulcer a prostaglandin deficiency disease?.Hum Pathol. 1986; 17: 106-107
- Pathogenesis of acute gastric stress ulcers.Am J Pathol. 1968; 52: 227-244
Article info
Publication history
Accepted:
April 1,
1996
Received:
February 1,
1996
Identification
Copyright
© 1996 Published by Elsevier Inc.
