Does the activation of poly (ADP-ribose) synthetase mediate tissue injury in the sepsis induced by cecal ligation and puncture?

Details

Serval ID
serval:BIB_18114
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Does the activation of poly (ADP-ribose) synthetase mediate tissue injury in the sepsis induced by cecal ligation and puncture?
Journal
Shock
Author(s)
Baechtold F., Scott J.A., Markert M., Mehta S., McCormack D.G., Anglada F., Galaud D., Vaglio M., Waeber B., Feihl F.
ISSN
1073-2322
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
16
Number
2
Pages
137-142
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
Poly (ADP-ribose) synthetase (PARS) is a DNA protective enzyme activated by single-strand breakage. It is suspected that exaggerated PARS activation related to biochemical stress by reactive oxygen and nitrogen species contributes to cellular injury in sepsis. The main hypothesis is that PARS activation leads to massive ATP and NAD consumption and consequent cellular energy depletion. The PARS inhibitor 3-amino-benzamide (3AB) is protective in rodents challenged with either endotoxin or intraperitoneal zymozan. The present experiment was designed to test the effect of 3AB in a more clinically relevant model of sepsis, namely polymicrobial sepsis induced by cecal ligature and puncture (CLP). Adult male Wistar rats were anesthetized, instrumented with catheters in the jugular vein and in the carotid artery, and then randomized into three groups: Sham (no laparotomy, n = 13), CLP (n = 15), and CLP/3AB (n = 18). All animals were allowed to recover and they received a continuous intravenous infusion of saline (20 mL/kg/h) and fentanyl (20 microg/kg/h). 3AB was administered to the CLP/3AB group as an intravenous bolus (10 mg/kg) followed by a continuous intravenous infusion (10 mg/kg/h). After 24 h, blood was drawn for the determination of biological indicators of organ injury. Rats were then anesthetized and biopsies of the liver were quickly frozen into liquid nitrogen for the subsequent determination of NAD and ATP levels. Further organ samples were collected for the assay of myeloperoxidase (MPO) to indicate tissue infiltration by leukocytes, and nitrotyrosine to indicate the level of biochemical stress by reactive nitrogen species. Twenty-four-hour mortality was 0/13 (Sham), 1/15 (CLP), and 5/18 (CLP/3AB; p = NS). In the surviving rats, CLP induced a clear elevation of liver enzymes, bilirubin, and pancreatic lipase, but not creatinine in the plasma, as well as a marked increase of MPO activity in liver, jejunum, and lung, but not kidney or heart. None of these variables was affected by treatment with 3AB. Furthermore, CLP did not cause depletion of NAD or ATP in the liver, nor any change in the nitrotyrosine content of any organ. These data argue against a general role of PARS activation in the pathogenesis of sepsis-induced tissue injury.
Keywords
Adenosine Triphosphate, Animals, Cecum, Creatine Kinase, Creatinine, Energy Metabolism, Enzyme Activation, Enzyme Inhibitors, Lipase, Liver Function Tests, Male, NADP, Oxygen, Partial Pressure, Peroxidase, Poly(ADP-ribose) Polymerases, Rats, Rats, Wistar, Reference Values, Sepsis, beta-Alanine
Pubmed
Web of science
Create date
19/11/2007 9:39
Last modification date
20/08/2019 12:48
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