Document Detail


Beneficial effects of 5-aminoisoquinolinone, a novel, potent, water-soluble, inhibitor of poly (ADP-ribose) polymerase, in a rat model of splanchnic artery occlusion and reperfusion.
MedLine Citation:
PMID:  15178366     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischemia-reperfusion and inflammation. Splanchnic artery occlusion and reperfusion causes an enhanced formation of reactive oxygen species which contribute to the pathophysiology of shock. The aim of the present study was to investigate the effects of 5-aminoisoquinolinone (5-AIQ), a potent water-soluble inhibitor of poly(ADP-ribose) polymerase (PARP), in the pathogenesis of splanchnic artery occlusion shock. Splanchnic artery occlusion shock was induced in rats by clamping both the superior mesenteric artery and the celiac artery for 45 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, all animals were sacrificed for histological examination and biochemical studies. Treatment of rats with 5-AIQ (3 mg/kg i.v.), attenuated the fall of mean arterial blood pressure caused by splanchnic artery occlusion shock. 5-AIQ also attenuated the ileum injury as well as the increase in the tissue levels of myeloperoxidase and malondialdehyde caused by splanchnic artery occlusion shock in the ileum. The immunohistochemical examination also demonstrated a marked increase in the immunoreactivity to PAR, nitrotyrosine, and intercellular adhesion molecule (ICAM-1) in the necrotic ileum from splanchnic artery occlusion-shocked rats. 5-AIQ treatment significantly reduced the increase of positive staining for PAR, nitrotyrosine and ICAM-I. In conclusion, these results show that 5-AIQ, a new water-soluble potent inhibitor of poly(ADP-ribose) polymerase, exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock.
Authors:
Rosanna Di Paola; Tiziana Genovese; Achille P Caputi; Mike Threadgill; Christoph Thiemermann; Salvatore Cuzzocrea
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  492     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-06-04     Completed Date:  2005-06-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  203-10     Citation Subset:  IM    
Affiliation:
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, via C. Valeria, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Celiac Artery
Disease Models, Animal
Intercellular Adhesion Molecule-1 / drug effects,  metabolism
Intestine, Small / blood supply*
Ischemia / etiology,  metabolism*,  pathology
Isoquinolines / pharmacology*
Lipid Peroxidation / drug effects
Male
Malondialdehyde / metabolism
Mesenteric Artery, Superior
Mesenteric Vascular Occlusion / complications*
Peroxidase / metabolism
Poly(ADP-ribose) Polymerases / antagonists & inhibitors*
Rats
Rats, Sprague-Dawley
Reperfusion
Reperfusion Injury / etiology,  metabolism*,  pathology
Solubility
Tyrosine / analogs & derivatives*,  antagonists & inhibitors
Water
Chemical
Reg. No./Substance:
0/5-aminoisoquinolinone; 0/Isoquinolines; 126547-89-5/Intercellular Adhesion Molecule-1; 3604-79-3/3-nitrotyrosine; 542-78-9/Malondialdehyde; 55520-40-6/Tyrosine; 7732-18-5/Water; EC 1.11.1.7/Peroxidase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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