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

Andrea Szabó, Andrew L. Salzman, Csaba Szabó

    Research output: Contribution to journalArticle

    34 Scopus citations

    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
    DOIs
    StatePublished - Oct 30 1998

    Keywords

    • Endothelium
    • Epithelium
    • Inflammation
    • Nitric oxide
    • Shock

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Pharmacology, Toxicology and Pharmaceutics(all)

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