Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase

B. Zingarelli, C. Szabó, A. L. Salzman

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Background - Oxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases. Aims - To study the role of nitric oxide (NO) derived from inducible NO synthase (iNOS) in an experimental model of murine enterocolitis. Methods - Tripitrobenzene sulphonic acid (TNBS) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls. The distal colon was evaluated for histological evidence of inflammation, iNOS expression and activity, tyrosine nitration and malondialdehyde formation (as indexes of nitrosative and oxidative stress), myeloperoxidase activity (as index of neutrophil infiltration), and tissue localisation of intercellular adhesion molecule 1 (ICAM-1). Results - TNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration, increased myeloperoxidase activity, increased concentrations of malondialdehyde, and an intense staining for nitrotyrosine and ICAM-1 in wild type mice. Genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage, and notably reduced nitrotyrosine formation and concentrations of malondialdehyde; it did not, however, affect neutrophil infiltration and intestinal ICAM-1 expression in the injured tissue. Conclusion - Data show that activation of iNOS is required for nitrosative and oxidative damage in experimental colitis.

Original languageEnglish (US)
Pages (from-to)199-209
Number of pages11
JournalGut
Volume45
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Inflammatory bowel disease
  • Intercellular adhesion molecule 1
  • Malondialdehyde
  • Nitric oxide
  • Nitric oxide synthase
  • Nitrotyrosine

ASJC Scopus subject areas

  • Gastroenterology

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