Apocynin decreases hydrogen peroxide and nirtate concentrations in exhaled breath in healthy subjects

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESS AbstractThe imbalance between reactive oxygen species (ROS) synthesis and antioxidants might be involved in the pathogenesis of many inflammatory diseases. NADPH oxidase, an enzyme responsible for ROS production, may represent an attractive therapeutic target to inhibit for the treatment of these diseases.Apocynin is an inhibitor of activation of NADPH oxidase complex present in the inflammatory cells.In double blind, placebo controlled, cross-over study, we investigated the effect of nebulized apocynin on ROS synthesis in 10 nonsmoking healthy volunteers. Apocynin (6 ml of 0.5 mg/ml) was administered by nebulization and its effects on H 2 O 2 , NO 2 -and NO 3 -generation were assessed after 30, 60 and 120 minutes by collecting exhaled breath condensate (EBC) samples using an EcoScreen analyzer. Additionally, respiratory parameters have been evaluated, utilizing spirometry and DLCO. We also analyzed peripheral blood differential counts and NO 2 -serum level, cough scale control and blood pressure as safety parameters. Thus, as apocynin significantly influence ROS concentration, it might have also antiinflammatory properties. As it is safe, it may have a potential to become a drug in airway inflammatory diseases treatment.

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

“…However, in vivo, a metabolite of this compound may act as a true NOX inhibitor, and it may show some specificity for NOX2. We and others have shown that nebulized apocynin is safe (142), prevented ozone-induced exacerbations of asthma, and decreased selected ROS and RNS in mild asthmatics and patients with COPD (117, 140, 141). Therefore, even the nonselective ROS-scavenging and NOXmodifying strategy might be beneficial in inflammatory airway disorders and deserves further clinical studies in clearly defined populations and with the reasonable caution of the possible adverse effects and cytotoxicity.…”

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

“…Subjects were asked to breathe at a normal frequency and tidal volume through a mouthpiece connected to a condenser for 20 minutes. The use of a nose clip during the collection of EBC was important (1) to prevent air inhalation through the nose (biomarker aerosols from the nasal epithelium might enter the inhaled air); (2) to prevent leakage from the lower airways through the nose; and (3) to prevent mixing of nasal and bronchial air [8,22], and finally (4) [17]. A nebulizer Pulmo Aide AP-50 (DeVilbiss, Richmond, VA) was used (mass median aerosol diameter 3.1 µm, output 0.3 mL/min) [17].…”

“…Moreover, there were no significant changes in blood pressure, heart rate value, and coughing scale before and after apocynin or placebo application (P > .05). Inhalation of apocynin or placebo aerosol did not have any effect on respiratory parameters [FEV 1 …”

“…Our previous study involving healthy subjects proved apocynin to be an effective anti-inflammatory drug, free of adverse effects when administered to healthy subjects [1]. Thus, in this study, the effects of apocynin nebulization on ROS and RNS production were investigated using the EBC of mild asthmatic patients.…”

“…In our previous study, we have proved that apocynin decreased H 2 O 2 (hydrogen peroxide) and NO − 3 (nitrates) concentrations in exhaled breath condensate (EBC) of healthy subjects [1]. Possibly, apocynin reacts with the thiol compounds of NADPH oxidase subunits.…”