Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats

doi:10.3748/wjg.v12.i4.568

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Jan 28, 2006 (publication date) through Jul 28, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Research

World J Gastroenterol. Jan 28, 2006; 12(4): 568-573
Published online Jan 28, 2006. doi: 10.3748/wjg.v12.i4.568

Attenuation of gastric mucosal inflammation induced by aspirin through activation of A_2A adenosine receptor in rats

Masaru Odashima, Michiro Otaka, Mario Jin, Koga Komatsu, Isao Wada, Youhei Horikawa, Tamotsu Matsuhashi, Natsumi Hatakeyama, Jinko Oyake, Reina Ohba, Sumio Watanabe, Joel Linden

Masaru Odashima, Michiro Otaka, Mario Jin, Koga Komatsu, Isao Wada, Youhei Horikawa, Tamotsu Matsuhashi, Natsumi Hatakeyama, Jinko Oyake, Reina Ohba, Sumio Watanabe, Department of Gastroenterology, Akita University School of Medicine, Akita, Japan

Joel Linden, Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United States

Correspondence to: Masaru Odashima, Department of Gastroenterology, Akita University School of Medicine, 1-1-1, Hondo, Akita City 010-8543, Japan. odashima@doc.med.akita-u.ac.jp

Telephone: +81-18-884-6104 Fax: +81-18-836-2611

Received: June 21, 2005
Revised: June 28, 2005
Accepted: July 15, 2005
Published online: January 28, 2006

Abstract

AIM: To determine whether a specific adenosine A_2A 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 HCl (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, 2.5-5 μg/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 after 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 A_2A receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.

Keywords: Aspirin, Pro-inflammatory cytokine, Adenosine A_2A receptor, ATL-146e, Gastric injury