Beneficial effects of GW274150 treatment on the development of experimental colitis induced by dinitrobenzene sulfonic acid

Rosanna Di Paola, Emanuela Mazzon, N. S A Patel, Tiziana Genovese, Carmelo Muià, Christoph Thiemermann, Angelina De Sarro, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory bowel disease is associated with inducible nitric oxide synthase (iNOS) expression, oxidative and nitrosative stress, and leukocyte infiltration in the colon. Here, we investigate the effects of the selective iNOS-inhibitor (S)-2-amino-(1-iminoethylamino)-5-thiopentanoic acid (GW274150) on the development of experimental colitis induced by dinitrobenzene sulfonic acid. When compared to dinitrobenzene sulfonic acid-treated mice, GW274150 (5 mg/kg i.p.)-treated mice subjected to dinitrobenzene sulfonic ACID-induced colitis experienced a significantly lower rate of the extent and severity of the histological signs of colon injury. Dinitrobenzene sulfonic acid-treated mice experienced hemorrhagic diarrhoea and weight loss. At 4 days after the administration of dinitrobenzene sulfonic acid, the mucosa of the colon exhibited large areas of necrosis. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) (PAR) showed an intense staining in the inflamed colon. Treatment of dinitrobenzene sulfonic acid-treated mice with GW274150 significantly reduced the degree of hemorrhagic diarrhoea and weight loss caused by administration of dinitrobenzene sulfonic acid. GW274150 also caused a substantial reduction of (i) the degree of colon injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in staining (immunohistochemistry) for nitrotyrosine, as well as (iv) PARP activation caused by dinitrobenzene sulfonic acid in the colon. Thus, GW274150 treatment reduced the degree of colitis caused by dinitrobenzene sulfonic acid. We propose that selective inhibition of iNOS activity with GW274150 may be useful in the treatment of inflammatory bowel disease.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalEuropean Journal of Pharmacology
Volume507
Issue number1-3
DOIs
Publication statusPublished - Jan 10 2005

Keywords

  • Inflammatory bowel disease
  • Nitric oxide synthase
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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