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

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• 作者：Peters ; Elisabeth A. ; Hiltermann ; Jeroen T.N. ; Stolk ; Jan
• 关键词：Oxidants ; NADPH oxidase ; Asthma ; Air pollution ; Ozone ; Airway hyperresponsiveness ; Apocynin ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2001
• 出版时间：December 1, 2001
• 年：2001
• 卷：31
• 期：11
• 页码：1442-1447
• 全文大小：86.4 K

文摘

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 O₃ at 2-week intervals. Apocynin (3 ml of 0.5 mg/ml) was inhaled 2 times before and 6 times after O₃ exposure at hourly intervals. At 36 h before and 16 h after O₃ exposure, methacholine inhalation challenge tests (Mch) were performed, and PC₂₀ and maximal % fall from baseline (MFEV₁) were calculated from dose-response curves. O₃-induced change in PC₂₀ (ΔPC₂₀) 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). O₃-induced ΔMFEV₁ was 11.9 ± 1.5 % (p = .008) during placebo inhalation and 3.85 ± 1.8 % during apocynin (p = .47). Apocynin reduced the ΔMFEV₁ by 8.05 % compared to placebo (p = .025). We conclude that apocynin markedly reduced O₃-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.