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

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Inflammation and inflammatory bowel disease
Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase
  1. B Zingarelli,
  2. C Szabó,
  3. A L Salzman
  1. Children’s Hospital Medical Centre, Division of Critical Care, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
  1. Dr Zingarelli.

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 Trinitrobenzene 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.

  • nitric oxide
  • nitric oxide synthase
  • inflammatory bowel disease
  • intercellular adhesion molecule 1
  • malondialdehyde
  • nitrotyrosine

  • Abbreviations used in this paper

    IBD
    inflammatory bowel disease
    ICAM-1
    intercellular adhesion molecule 1
    iNOS
    inducible nitric oxide synthase
    NO
    nitric oxide
    TNBS
    trinitrobenzene sulphonic acid

    • https://doi.org/10.1136/gut.45.2.199

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    • Abbreviations used in this paper

      IBD
      inflammatory bowel disease
      ICAM-1
      intercellular adhesion molecule 1
      iNOS
      inducible nitric oxide synthase
      NO
      nitric oxide
      TNBS
      trinitrobenzene sulphonic acid
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