NOX, a novel nitric oxide scavenger, reduces bacterial translocation in rats after endotoxin challenge

Eva Dickinson, Recep Tuncer, Evan Nadler, Patricia Boyle, Sean Alber, Simon Watkins, Henri Ford

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Endotoxemia promotes gut barrier failure and bacterial translocation (BT) by upregulating inducible nitric oxide synthase (iNOS) in the gut. We hypothesized that administration of a dithiocarbamate derivative, NOX, which scavenges nitric oxide (NO), may reduce intestinal injury and BT after lipopolysaccharide (LPS) challenge. Sprague-Dawley rats were randomized to receive NOX or normal saline via subcutaneously placed osmotic pumps before or after LPS challenge. Mesenteric lymph nodes, liver, spleen, and blood were cultured 24 h later. Transmucosal passage of Escherichia coli C-25 or fluorescent beads were measured in an Ussing chamber. Intestinal membranes were examined morphologically for apoptosis, iNOS expression, and nitrotyrosine immunoreactivity. NOX significantly reduced the incidence of bacteremia, BT, and transmucosal passage of bacteria and beads when administered before or up to 12 h after LPS challenge. LPS induced enterocyte apoptosis at the villus tips where bacterial entry was demonstrated by confocal microscopy. NOX significantly decreased the number of apoptotic nuclei and nitrotyrosine residues. NOX prevents LPS-induced gut barrier failure by scavenging NO and its toxic derivative, peroxynitrite.

Original languageEnglish (US)
Pages (from-to)G1281-G1287
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume277
Issue number6 40-6
DOIs
StatePublished - Dec 1999

Keywords

  • Aminoguanidine
  • Dithiocarbamate
  • Intesti nal permeability
  • Lipopolysaccharide
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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