Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats

Salvatore Cuzzocrea, Emanuela Mazzon, Ivana Serraino, Laura Dugo, Tommaso Centorrino, Antonio Ciccolo, Lidia Sautebin, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory bowel disease is characterised by oxidative and nitrosative stress, leukocyte infiltration, upregulation of the expression of intercellular adhesion molecule 1 (ICAM-1) and upregulation of P-selectin in the colon. Here, we investigate the effects of the selective cyclo-oxygenase-2 inhibitor, celecoxib, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced hemorrhagic diarrhoea and weight loss. At 4 days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology, as well as an increase in myeloperoxidase activity in the mucosa) was associated with upregulation of ICAM-1 and P-selectin, as well as high tissue levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) polymerase showed intense staining in the inflamed colon. Celecoxib (5 mg/kg twice a day orally) significantly reduced the degree of hemorrhagic diarrhoea and the weight loss caused by administration of DNBS. Celecoxib also caused a substantial reduction of (i) the degree of colonic injury, (ii) the rise in myeloperoxidase activity (mucosa), (iii) the increase in the tissue levels of malondialdehyde, (iv) the increase in staining (immunohistochemistry) for nitrotyrosine, as well as (v) the upregulation of ICAM-1 and P-selectin caused by DNBS in the colon. Thus, we provide the first evidence that a selective cyclo-oxygenase-2 inhibitor celecoxib reduces the degree of colitis caused by DNBS.

Original languageEnglish
Pages (from-to)91-102
Number of pages12
JournalEuropean Journal of Pharmacology
Volume431
Issue number1
DOIs
Publication statusPublished - Nov 9 2001

Keywords

  • Colon damage
  • Cyclo-oxygenase-2
  • DNBS (Dinitrobenzene sulfonic acid)
  • Free radicals
  • Inflammation
  • Nitric oxide (NO)
  • Peroxynitrite
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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