Beneficial effects of GPI 6150, an inhibitor of poly(ADP-ribose) polymerase in a rat model of splanchnic artery occlusion and reperfusion

Shock
E MazzonS Cuzzocrea

Abstract

The aim of the present study was to investigate the effects of GPI 6150, a new poly(ADP-ribose) polymerase (PARP) inhibitor, in the pathogenesis of splanchnic artery occlusion (SAO) shock. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by reperfusion. At 60 min after reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood pressure, significant increase of tissue myeloperoxidase activity (111 +/- 4.3 U/100 mg wet tissue vs. 28 +/- 3.2 U/100 mg wet tissue of sham-operated rats), and marked histological injury to the distal ileum and a significant mortality (0% survival at 2 h after reperfusion). Immuno-histochemical examination demonstrated a marked increase in the immunoreactivity to PARP, P-selectin, and intercellular adhesion molecule (ICAM-1) in the necrotic ileum. GPI 6150 treatment significantly improved mean arterial blood pressure, prevented the infiltration of neutrophils (72 +/- 3.6 U/100 mg wet tissue) into the reperfused intestine, improved the histological status of the reperfused tissues, markedly reduced the intensity of P-selectin and ICAM-1 in tissue section from SAO-shocked rats, and improved survival. In conclusio...Continue Reading

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Citations

Aug 24, 2006·Intensive Care Medicine·Eberhard BarthCsaba Szabó
Feb 5, 2009·Intensive Care Medicine·Ke-Xuan LiuZhengyuan Xia
Jul 31, 2003·Pharmacology & Therapeutics·Ian A Clark, William B Cowden
May 24, 2003·Best Practice & Research. Clinical Gastroenterology·Jeroen J Kolkman, Peter B F Mensink
May 3, 2005·Nature Reviews. Drug Discovery·Prakash Jagtap, Csaba Szabó
Dec 17, 2003·Shock·Stefania MarzoccoSalvatore Cuzzocrea
Jul 20, 2004·Clinical Microbiology Reviews·Ian A ClarkWilliam B Cowden
Jun 6, 2006·Medicinal Research Reviews·Ana OlmosSalvador Máñez
Nov 29, 2005·European Journal of Pharmacology·Rosanna Di PaolaSalvatore Cuzzocrea
May 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Kishor Devalaraja-NarashimhaBabu J Padanilam
Jul 19, 2002·Biochemical Pharmacology·Emanuela MazzonSalvatore Cuzzocrea
Jun 5, 2015·Journal of Veterinary Emergency and Critical Care·Hope F DouglasRalph G Meyer
Feb 24, 2011·Multiple Sclerosis : Clinical and Laboratory Research·Leonardo CavoneAlberto Chiarugi
Oct 30, 2004·Stroke; a Journal of Cerebral Circulation·Eun-Mi ParkCostantino Iadecola
Jan 13, 2005·The Journal of Pharmacology and Experimental Therapeutics·Tiziana GenoveseSalvatore Cuzzocrea
Feb 1, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Terézia B AndrásiSiegfried Hagl
Mar 26, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Salvatore CuzzocreaZhao-Qi Wang
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alessandra AldinucciAlberto Chiarugi

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