Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents

Details

Serval ID
serval:BIB_E596C9C7C005
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents
Journal
Biochemical Pharmacology
Author(s)
Pacher  P., Cziraki  A., Mabley  J. G., Liaudet  L., Papp  L., Szabo  C.
ISSN
0006-2952 (Print)
Publication state
Published
Issued date
12/2002
Volume
64
Number
12
Pages
1785-91
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec 15
Abstract
Reactive oxygen and nitrogen species are overproduced in the cardiovascular system during circulatory shock. Oxidant-induced cell injury involves the activation of poly(ADP-ribose) polymerase (PARP). Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the new potent phenanthridinone PARP inhibitor PJ34 [the hydrochloride salt of N-(oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide], we studied whether the impaired cardiac function in endotoxic shock is dependent upon the PARP pathway. Escherichia coli endotoxin (lipopolysaccharide, LPS) at 55 mg/kg, i.p., induced a severe depression of the systolic and diastolic contractile function, tachycardia, and a reduction in mean arterial blood pressure in both rats and mice. Treatment with PJ34 significantly improved cardiac function and increased the survival of rodents. In addition, LPS-induced depression of left ventricular performance was significantly less pronounced in PARP-1 knockout mice (PARP(-/-)) as compared with their wild-type littermates (PARP(+/+)). Thus, PARP activation in the cardiovascular system is an important contributory factor to the cardiac collapse and death associated with endotoxin shock.
Keywords
Animals Death Disease Models, Animal Drug Interactions Endotoxins/*toxicity Enzyme Activation Gene Deletion Heart Diseases/chemically induced/*enzymology/mortality Heart Function Tests Lipopolysaccharides/pharmacology Male Mice Phenanthrenes/pharmacology Poly(ADP-ribose) Polymerases/antagonists & inhibitors/genetics/*physiology Rats Rats, Wistar
Pubmed
Web of science
Create date
24/01/2008 17:01
Last modification date
20/08/2019 16:08
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