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Selected Publication:
Maricic, N; Ehrlich, K; Gretzer, B; Schuligoi, R; Respondek, M; Peskar, BM.
Selective cyclo-oxygenase-2 inhibitors aggravate ischaemia-reperfusion injury in the rat stomach.
Br J Pharmacol. 1999; 128(8):1659-1666
Doi: 10.1038/sj.bjp.0702966
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- Co-authors Med Uni Graz
- Schuligoi Rufina
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cyclooxygenase 1 -
- Cyclooxygenase 2 -
- Cyclooxygenase 2 Inhibitors -
- Cyclooxygenase Inhibitors - adverse effects
- Dose-Response Relationship, Drug - adverse effects
- Furans - adverse effects
- Gastric Mucosa - drug effects
- Indomethacin - adverse effects
- Isoenzymes - metabolism
- Male - metabolism
- Membrane Proteins - metabolism
- Nitrobenzenes - adverse effects
- Prostaglandin-Endoperoxide Synthases - metabolism
- Prostaglandins - therapeutic use
- RNA, Messenger - drug effects
- Rats - drug effects
- Rats, Wistar - drug effects
- Reperfusion Injury - chemically induced
- Sulfonamides - adverse effects
- Find related publications in this database (Keywords)
- cyclo-oxygenase-1
- cyclo-oxygenase-2
- ischaemia-reperfusion
- NS-398
- DFU
- dexamethasone
- indomethacin
- gastric mucosal damage