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Peskar, BM; Ehrlich, K; Peskar, BA.
Interaction of cyclooxygenase-2 inhibitors and salicylate in gastric mucosal damage.
Eur J Pharmacol. 2002; 434(1-2):65-70 Doi: 10.1016/S0014-2999(01)01524-2
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Leading authors Med Uni Graz: Peskar Bernhard
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Abstract:: The interactions of sodium salicylate and the selective cyclooxygenase-2 inhibitors N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) and 5.5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5II)-furanone (DFU), dexamethasone and the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methylester (L-NAME) were examined in ischaemia-reperfusion damage and adaptive protection in the rat stomach. Ischaemia-reperfusion damage was substantially aggravated by pretreatment with NS-398 (4 mg/kg), DFU (2 mg/kg), dexamethasone (1 mg/kg) or L-NAME (3 and 10 mg/kg). Salicylate (0.01-0.05 mg/kg) reversed the aggravating effect of NS-398, DFU and dexamethasone, while the effect of L-NAME was counteracted by L-arginine (twice 400 mg/kg) but not salicylate (0.05 or 10 mg/kg). Instillation of 20% ethanol prevented mucosal damage induced by 70% ethanol. This adaptive gastroprotection was abolished by pretreatment with NS-398 (1 mg/kg), DFU (0.2 mg/kg) or L-NAME (10 mg/kg). Salicylate (0.01-0.05 mg/kg) reversed the inhibition of protection by NS-398 and DFU, while the effect of L-NAME (10 mg/kg) was antagonized by L-arginine (100 mg/kg) but not salicylate (0.05 mg/kg). The precise mechanism of the functional antagonism between extremely low doses of salicylate and selective cyclooxygenase-2 inhibitors remains to be investigated.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Cyclooxygenase 2 -; Cyclooxygenase 2 Inhibitors -; Cyclooxygenase Inhibitors - pharmacology; Cytoprotection - pharmacology; Drug Interactions - pharmacology; Ethanol - toxicity; Furans - pharmacology; Gastric Mucosa - drug effects; Isoenzymes - drug effects; Male - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - physiology; Nitrobenzenes - pharmacology; Prostaglandin-Endoperoxide Synthases - drug effects; Rats - drug effects; Rats, Wistar - drug effects; Sodium Salicylate - pharmacology; Sulfonamides - pharmacology
Find related publications in this database (Keywords): sodium salicylate; cyclooxygenase-2; gastric mucosal damage; ischaemia-reperfusion; adaptive gastroprotection; nitric oxide (NO)