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

The 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 H2O2, NO2- and NO3- generation were assessed after 30, 60 and 120 min 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 NO2- serum level, cough scale control and blood pressure as safety parameters. Apocynin caused reduction of H2O2 concentration in EBC as compared to placebo, after 60 min. of inhalation (0.18 mu M vs. 0.31 mu M, p < 0.05) as well as after 120 min. (0.2 mu M vs. 0.31 mu M, p < 0.05). Similarly, apocynin significantly decreased concentration of NO3- as compared to placebo, after 60 and 120 min. (6.8 mu M vs. 14.4 mu M and 6.5 mu M vs. 14.9 mu M respectively, p < 0.05). Apocynin was well tolerated and no adverse events have been observed throughout the study. Thus, as apocynin significantly influence ROS concentration, it might have also and inflammatory properties. As it is safe, it may have a potential to become a drug in airway inflammatory diseases treatment. (C) 2009 Elsevier Ltd. All rights reserved.