Poly (ADP-ribose) synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock

Andrea Szabó, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Endotoxin shock is known to impair critical cellular functions and is associated with the development of multiple organ dysfunction. Recent in vitro and in vivo studies demonstrated that oxidants produced during shock and inflammation trigger the activation of the nuclear enzyme pony (ADP- ribose) synthetase (PARS), resulting in intracellular energetic failure and tissue dysfunction. Here we examined the role of PARS activation in the development of barrier dysfunction of the intestine and lung during endotoxemia in rats. Ileal mucosal permeability was assessed by the measurement of the lumen to plasma directional passage of the hydrophil solute sodium fluorescein. Microvascular permeability in the lung was examined by the measurement of the extravasation of Evans blue. Inhibition of PARS was achieved by treating the animals with 3-aminobenzamide 30 min prior and 3 hr after lipopolysaccharide injection (10 mg/kg). Endotoxemia (E. coli bacterial lipopolysaccharide, 5-10 mg/kg) resulted in an increased epithelial permeability in the ileum and a microvascular hyperpermeability and neutrophil accumulation in the lung in 6 hr. The PARS inhibitor 3- aminobenzamide significantly reduced the lipopolysaccharide-induced hyperpermeability in both organs, without affecting neutrophil deposition. Thus, PARS activation plays a role in mediating endothelial and epithelial dysfunction and hyperpermeability during endotoxin shock.

Original languageEnglish (US)
Pages (from-to)2133-2139
Number of pages7
JournalLife Sciences
Volume63
Issue number23
StatePublished - Oct 30 1998
Externally publishedYes

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Adenosine Diphosphate Ribose
Poly Adenosine Diphosphate Ribose
Ligases
Endotoxins
Shock
Chemical activation
Lung
Lipopolysaccharides
Endotoxemia
Permeability
Neutrophils
Evans Blue
Enzyme Activation
Capillary Permeability
Fluorescein
Ileum
Oxidants
Escherichia coli
Intestines
Rats

Keywords

  • Endothelium
  • Epithelium
  • Inflammation
  • Nitric oxide
  • Shock

ASJC Scopus subject areas

  • Pharmacology

Cite this

Poly (ADP-ribose) synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock. / Szabó, Andrea; Salzman, Andrew L.; Szabo, Csaba.

In: Life Sciences, Vol. 63, No. 23, 30.10.1998, p. 2133-2139.

Research output: Contribution to journalArticle

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