Apocynin reduces reactive oxygen species concentrations in exhaled breath condensate in asthmatics

Abstract

Asthma is an inflammatory airway disease, and oxidative stress was proven to be involved in its pathogenesis. Apocynin effectively inhibits the main source of reactive oxygen species (ROS)-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-by blocking its activation. The aim of this study was to investigate the effect of inhaled apocynin on ROS and RNS (reactive nitrogen species) concentration in 14 nonsmoking mild asthmatics. Effects of nebulized apocynin (0.5 mg/mL) were assessed in exhaled breath condensate (EBC) after 30, 60, and 120 minutes, and safety parameters have been analyzed. Apocynin significantly decreased H2O2 concentration in EBC in comparison with placebo after 60 and 120 minutes. Moreover, apocynin significantly reduced NO(-2) concentration 30 and 60 minutes after nebulization and caused a significant decrease of NO(-3) concentration in EBC 60 and 120 minutes after administration, comparing with placebo. No adverse events have been observed throughout the study. This research confirmed anti-inflammatory properties of nebulized apocynin, which might be an effective and safe drug in bronchial asthma.

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

“…Consistent with the involvement of NOX2, inhaled corticosteroids that relieve symptoms also diminished NOX2 mRNA expression in circulating leukocytes from asthmatics. Administration of the NOX2 inhibitor apocynin to asthmatic patients led to decreased H 2 O 2 levels in exhaled breath condensates (284). In guinea pigs, ebselen, a potent NOX2 inhibitor (276,338), was able to improve the ovalbumin-induced asthmatic inflammatory responses, consistent with a role for NOX2 (276,338).…”

“…In a model of strokeprone spontaneously hypertensive rats, apocynin significantly decreased the occurrence of stroke (332). In addition, apocynin has been investigated in a Phase 2 human clinical trial for asthma (284), where it showed anti-inflammatory properties, including a decrease in H 2 O 2 in exhaled breath condensates. Thus, while apocynin shows promise as an anti-inflammatory molecule, it remains unclear as to whether its primary mode of action in vivo involves the inhibition of NOX2, its antioxidant properties, or both.…”

NOX Modifiers—Just a Step Away from Application in the Therapy of Airway Inflammation?

“…We and others have shown that these markers are useful for noninvasive monitoring to the extent of oxidative stress in the airways. We have also shown that apocynin significantly decreases selected ROS and reactive nitrogen species (RNS) in mild asthmatics (141).…”

In-vivo evaluation of apocynin for prevention of Helicobacter pylori-induced gastric carcinogenesis

“…Apocynin treatment in a marmoset model of Parkinson's disease mitigated the disease progression, limiting the parkinsonian signs and motor-function deterioration (Philippens et al, 2013). Moreover, a clinical trial using nebulized apocynin demonstrated a reduction of ROS concentrations in the exhaled breath condensate of asthma patients (Stefanska et al, 2012).…”

“…Besides the direct inhibition of neutrophil NADPH oxidase, apocynin prevents the activation of NF-ĸB, which is an important mediator of gastric inflammation (Barnes and Larin, 1997;Lafeber et al, 1999). Apocynin has already been preclinically investigated to tackle inflammatory disorders, such as Parkinson's and Alzheimer's disease, and proved to inhibit airway inflammation in a clinical trial with asthma patients (Lull et al, 2011;Ghosh et al, 2012;Stefanska et al, 2012). This study assessed the anti-inflammatory activity of apocynin in the Mongolian gerbil model for H. pylori-induced gastric disease.…”