Endotoxin-induced ileal mucosal injury and nitric oxide dysregulation are temporally dissociated

Elliott D. Crouser, Mark W. Julian, David M. Weinstein, Ruairi J. Fahy, John A. Bauer

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Despite recent investigations, the mechanisms responsible for intestinal epithelial injury during endotoxemia remain unclear. The present study tests the hypothesis that epithelial necrosis and/or apoptosis correlate with nitric oxide (NO) dysregulation in a nonischemic model of sepsis-induced ileal injury. To test this hypothesis, a well-established in situ, autoperfused, feline ileal preparation was employed. After endotoxin (lipopolysaccharide [LPS], 3 mg/kg, intravenously; n = 9) or vehicle (control; n = 5) treatment, ileal segments were obtained at baseline, 2 and 4 h for simultaneous evaluations of cellular and mitochondrial ultrastructure, immunoprevalence of inducible nitric oxide synthase (iNOS) and 3- nitrotyrosine (a stable biomarker of peroxynitrite), and histochemical evidence of apoptosis. Epithelial necrosis was prominent by 2 h post-LPS, despite unaltered global ileal tissue oxygen content, blood volume, and blood flow. Significant evidence of apoptosis and increases in the immunoprevalence of iNOS and 3-nitrotyrosine were not evident until 4 h post-LPS. These results suggest that the early ileal mucosal necrosis may be due to LPS- induced activation of inflammatory pathways and/or microcirculatory disturbances, whereas NO dysregulation may participate in later events, including protein nitration and epithelial apoptosis.

Original languageEnglish
Pages (from-to)1705-1712
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number5
StatePublished - 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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