Budesonide reduces superoxide and peroxynitrite anion chemiluminescence during human neutrophil bursts

Pier Carlo Braga, Monica Dal Sasso, Maria Culici, Tiziana Bianchi, Enrico Eugenio Guffanti

Research output: Contribution to journalArticle

Abstract

Many lung disorders are characterized by airway inflammation involving the recruitment of inflammatory cells, and leading to the release of oxidant and inflammatory mediators. The overproduction of superoxide anion (O 2.-) and nitric oxide (NO) during the respiratory bursts of neutrophils leads to production of peroxynitrite, a highly damaging oxidant with an important role in the inflammatory loop causing airway hyper-reactivity in respiratory diseases like asthma. The aim of this study was to investigate in vitro the effects of a 1-hour incubation with budesonide at 2.5 × 10 -7, 5 × 10-7, 1 × 10-6, 2 × 10-6 and 4 × 10-6 mol/l on O2 .-, NO, and peroxynitrite production during the respiratory burst of human neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5 × 10-7 mol/l) orphorbol 12-myristate 13-acetate (PMA, 2 × 10-6 mol/l), as documented by luminol-amplified chemiluminescence (LACL). In absence of L-arginine, budesonide (5 × 10-7 to 4 × 10-6 mol/l) dose-dependently reduced both fMLP- and PMA-induced LACL (18.3-50.6%). In the presence of L-arginine (100 μg/ml), a NO donor increasing peroxynitrite production, LACL increased 3-5 times compared with baseline, but budesonide dose-dependently reduced LACL (25.5-59.6%). Mifepristone (4 × 10-6 mol/l), a glucocorticoid receptor antagonist, inhibited the effect of budesonide on LACL, thus confirming that budesonide reacts with glucocorticoid receptors to exert an antioxidant activity. These results suggest that budesonide target rapidly human neutrophils leading to a fast reduction in both NO and peroxynitrite production, and are consistent with decrease in exhaled NO levels after treatment with budesonide in patients with asthma.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalPharmacology
Volume75
Issue number4
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Budesonide
  • Luminol-amplified chemiluminescence
  • Nitric oxide
  • Peroxynitrite
  • Polymorphonuclear neutrophils
  • Superoxide anion

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Braga, P. C., Dal Sasso, M., Culici, M., Bianchi, T., & Guffanti, E. E. (2005). Budesonide reduces superoxide and peroxynitrite anion chemiluminescence during human neutrophil bursts. Pharmacology, 75(4), 179-186. https://doi.org/10.1159/000088623