Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics

E A Peters, J T Hiltermann, J Stolk

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Abstract

Apocynin is an inhibitor of NADPH oxidase present in inflammatory cells such as eosinophils and neutrophils. We investigated the effect of inhaled apocynin on ozone-induced bronchial hyperresponsiveness in vivo. Seven mild atopic asthmatics participated in a placebo-controlled, cross-over study with two exposures to O(3) at 2-week intervals. Apocynin (3 ml of 0.5 mg/ml) was inhaled 2 times before and 6 times after O(3) exposure at hourly intervals. At 36 h before and 16 h after O(3) exposure, methacholine inhalation challenge tests (Mch) were performed, and PC(20) and maximal % fall from baseline (MFEV(1)) were calculated from dose-response curves. O(3)-induced change in PC(20) (Delta PC(20)) after placebo treatment was -1.94 +/- 0.39 DD (mean +/- SEM doubling dose Mch) (p =.001) and apocynin was -0.6 +/- 0.33 DD (p =.17). The difference between apocynin and placebo treatment was 1.3 DD +/- 0.42 (p =.02). O(3)-induced Delta MFEV(1) was 11.9 +/- 1.5% (p =.008) during placebo inhalation and 3.85 +/- 1.8% during apocynin (p =.47). Apocynin reduced the Delta MFEV(1) by 8.05% compared to placebo (p =.025). We conclude that apocynin markedly reduced O(3)-induced hyperreactivity for Mch as well as maximal airway narrowing. The results suggest that apocynin may have a role in preventing ozone-induced exacerbations of asthma.

Original languageEnglish
Pages (from-to)1442-1447
Number of pages6
JournalFree Radical Biology and Medicine
Volume31
Issue number11
DOIs
Publication statusPublished - 1-Dec-2001
Externally publishedYes

Keywords

  • Acetophenones
  • Administration, Inhalation
  • Adult
  • Aerosols
  • Antioxidants
  • Asthma
  • Bronchial Hyperreactivity
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enzyme Inhibitors
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Methacholine Chloride
  • NADPH Oxidase
  • Ozone
  • Placebos
  • Clinical Trial
  • Controlled Clinical Trial
  • Journal Article
  • Research Support, Non-U.S. Gov't

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