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Olprinone attenuates the development of ischemia/reperfusion injury of the gut

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Abstract

Purpose

Splanchnic artery occlusion (SAO) shock is a severe form of circulatory shock produced by ischemia and reperfusion of the splanchnic organs. The occlusion and reperfusion of the splanchnic arteries causes activation and adhesion of polymorphonuclear neutrophils (PMNs), release of proinflammatory substances and the formation of both species of oxygen and nitrogen derivatives free radicals. Olprinone is a specific phosphodiesterase-III inhibitor that has many properties; one of which is anti-inflammatory actions at therapeutic concentrations clinically used for heart failure. In this study, we wanted to evaluate the pharmacological action of olprinone (a PDEIII inhibitor) on SAO shock in mice.

Methods

SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. Olprinone was given at a dose of 0.2 mg/kg i.p. 15 min before reperfusion.

Results

Our results indicated that olprinone up-regulated cAMP in injured ileum tissue, and decreased the ileum tissue damage after 1 h of reperfusion in SAO shock mice. Moreover, olprinone decreased NF-κB expression; the nitration of tyrosine residues; the phosphorylation of p38 MAPK and JNK; cytokine production (TNF-α and IL-1β); ICAM-1 and P-selectin expression and apoptosis in the injured ileum.

Conclusions

These results could imply a future use of olprinone in the therapy of ischemia and reperfusion shock.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100, Messina, Italy

    Concetta Crisafulli & Salvatore Cuzzocrea

  2. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy

    Emanuela Mazzon, Maria Galuppo, Irene Paterniti & Salvatore Cuzzocrea

  3. Department of Human Pathology, School of Medicine, University of Messina, Messina, Italy

    Rocco Caminiti

Authors
  1. Concetta Crisafulli
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  2. Emanuela Mazzon
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  3. Maria Galuppo
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  4. Irene Paterniti
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  5. Rocco Caminiti
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  6. Salvatore Cuzzocrea
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Corresponding author

Correspondence to Salvatore Cuzzocrea.

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Crisafulli, C., Mazzon, E., Galuppo, M. et al. Olprinone attenuates the development of ischemia/reperfusion injury of the gut. Intensive Care Med 36, 1235–1247 (2010). https://doi.org/10.1007/s00134-010-1798-4

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  • DOI: https://doi.org/10.1007/s00134-010-1798-4

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