Modulation by heme and zinc protoporphyrin of colonic heme oxygenase-1 and experimental inflammatory bowel disease in the rat

Csaba Varga, Ferenc Laszlo, Peter Fritz, Maryan Cavicchi, Dominique Lamarque, Krisztina Horvath, Aniko Posa, Aniko Berko, Brendan J.R. Whittle

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Reactive oxygen species, suggested to be involved in inflammatory bowel disease, may be modulated by endogenous anti-oxidant products of heme oxygenase-1 (HO-1). In the present work, HO-1 expression in trinitrobenzene sulphonic acid (TNBS)-induced colitis in the rat and the effects of HO-1 modulation, particularly by the HO-1 inducer, heme, were further evaluated. Colitis was induced by intracolonic challenge with TNBS and assessed macroscopically and by myeloperoxidase (MPO) assay. Heme oxygenase activity was determined by measurement of bilirubin formation and HO-1 protein expression was determined by Western blotting. TNBS challenge led to an early and substantial induction of HO-1 protein expression and heme oxygenase activity in the colon that peaked after 48-72 h and declined over 10 days. Heme (30 μmol/kg/day, s.c) increased colonic HO-1 protein expression and enzyme activity and decreased colonic damage and myeloperoxidase activity. Short-term administration of cadmium chloride (2 mg/kg, s.c.), another known HO-1 inducer, also reduced the colonic injury and myeloperoxidase levels. In contrast, the HO-1 inhibitor, zinc protoporphyrin (50 μmol/kg/day, s.c) significantly increased the colonic damage and myeloperoxidase activity over 10 days, as did tin protoporphyrin (30 μmol/kg/day, s.c). These results support the proposal that induction of HO-1 provides a protective mechanism in this model under both acute and more-chronic conditions, and that its selective up-regulation could thus be of therapeutic potential in colitis.

Original languageEnglish
Pages (from-to)164-171
Number of pages8
JournalEuropean Journal of Pharmacology
Volume561
Issue number1-3
DOIs
Publication statusPublished - Apr 30 2007

Keywords

  • Cadmium chloride
  • Heme
  • Heme oxygenase-1
  • Inflammatory bowel disease
  • TNBS colitis
  • Tin protoporphyrin
  • Trinitrobenzene sulphonic acid
  • Zinc protoporphyrin

ASJC Scopus subject areas

  • Pharmacology

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