Selective cyclo-oxygenase-2 inhibitors aggravate ischaemia-reperfusion injury in the rat stomach.
Br J Pharmacol
; 128(8): 1659-66, 1999 Dec.
Article
en En
| MEDLINE
| ID: mdl-10588920
1. Effects of indomethacin, the selective cyclo-oxygenase (COX)-2 inhibitors NS-398 and DFU, and dexamethasone on gastric damage induced by 30 min ischaemia followed by 60 min reperfusion (I-R) were investigated in rats. Modulation of gastric levels of COX-1 and COX-2 mRNA by I-R was evaluated using Northern blot and reverse transcription-polymerase chain reaction. 2. I-R-induced gastric damage was dose-dependently aggravated by administration of indomethacin (1 - 10 mg kg(-1)), NS-398 (0.4 - 4 mg kg(-1)) or DFU (0.02 - 2 mg kg(-1)) as assessed macroscopically and histologically. 3. Likewise, administration of dexamethasone (1 mg kg(-1)) significantly increased I-R damage. 4. Low doses of 16, 16-dimethyl-prostaglandin(PG)E(2), that did not protect against ethanol-induced mucosal damage, reversed the effects of the selective COX-2 inhibitors, indomethacin and dexamethasone. 5. I-R had no effect on gastric COX-1 mRNA levels but increased COX-2 mRNA levels in a time-dependent manner. Dexamethasone inhibited the I-R-induced expression of COX-2 mRNA. 6. I-R was not associated with a measurable increase in gastric mucosal formation of 6-keto-PGF(1alpha) and PGE(2). PG formation was substantially inhibited by indomethacin (10 mg kg(-1)) but was not significantly reduced by NS-398 (4 mg kg(-1)), DFU (2 mg kg(-1)) or dexamethasone (1 mg kg(-1)). 7. The findings indicate that selective COX-2 inhibitors and dexamethasone markedly enhance gastric damage induced by I-R. Thus, whereas COX-2 has no essential role in the maintenance of gastric mucosal integrity under basal conditions, COX-2 is rapidly induced in a pro-ulcerogenic setting and contributes to mucosal defence by minimizing injury. This suggests that in certain situations selective COX-2 inhibitors may have gastrotoxic effects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfonamidas
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Daño por Reperfusión
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Indometacina
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Inhibidores de la Ciclooxigenasa
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Prostaglandina-Endoperóxido Sintasas
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Furanos
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Isoenzimas
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Nitrobencenos
Límite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Año:
1999
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido