Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats
AIM: To determine whether a specific adenosine A2A receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines. METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg/kg)...
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Veröffentlicht in: | World journal of gastroenterology : WJG 2006-01, Vol.12 (4), p.568-573 |
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Zusammenfassung: | AIM: To determine whether a specific adenosine A2A receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines.
METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCI (0.15 mol/L, 8.0 mL/kg). 4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4- dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2- ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e, 2.5-5μg/kg, IP) was injected 30 min before the administration of aspirin. Tissue myeloperoxidase (MPO) concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion. RESULTS: Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions (ulcer index) in control rats was 29.8±7.75 mm and was reduced to 3.8±1.42 mm alter pretreatment with 5.0 g/kg ATL-146e (P〈 0.01). The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e. CONCLUSION: The specific adenosine A2A receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties. |
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ISSN: | 1007-9327 2219-2840 |
DOI: | 10.3748/wjg.v12.i4.568 |