Adenosine a2a receptor-selective stimulation reduces signaling pathways involved in the development of intestine ischemia and reperfusion injury

Rosanna Di Paola, Alessia Melani, Emanuela Esposito, Emanuela Mazzon, Irene Paterniti, Placido Bramanti, Felicita Pedata, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

In the present study, we tested the efficacy of treatment with the selective adenosine A2A receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]- 50-ethylcarboxamidoadenosine (CGS 21680) on ischemia and reperfusion injury of the multivisceral organs. Ischemia and reperfusion injury was induced in mice by clamping both the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by reperfusion. Sixty minutes after reperfusion, animals were killed for histological examination and biochemical studies. Injured vehicle-treated mice developed a significant increase of ileum TNF-α levels, myeloperoxidase activity, and marked histological injury and apoptosis. Ischemia and reperfusion injury of the multivisceral organs was also associated with significant mortality. Reperfused ileum sections from injured vehicle-treated mice showed positive staining for P-selectin and intercellular adhesion molecule 1. The intensity and degree of P-selectin and intercellular adhesion molecule 1 were markedly reduced in tissue sections from injured CGS 21680-treated mice. Ischemia and reperfusion-injured mice that have been treated with CGS 21680 showed also a significant reduction of neutrophil infiltration into the intestine, a reduction of apoptosis, and improved histological status of the intestine and survival. Taken together, our results clearly demonstrate that selective activation of adenosine A2A receptors plays an important role in the regulation of ischemia and reperfusion injury and results put forward the hypothesis that selective activation of adenosine A2A receptors may represent a novel and possible strategy.

Original languageEnglish
Pages (from-to)541-551
Number of pages11
JournalShock
Volume33
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • A receptors
  • CGS 21680
  • ICAM
  • Neutrophil infiltration
  • SAO

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine
  • Medicine(all)

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