Abstract
Lung-protective pharmacotherapies preventing development of bronchopulmonary dysplasia (BPD) in infants are widely investigated. The aim of this study was to evaluate the influence of inhaled N-acetylcysteine (NAC) on the oxidative and protease imbalance in lungs of newborn guinea pigs under prolonged hyperoxia. The studied groups included: “hyperoxia” (n=12, 70% O2, 14 days), “hyperoxia+NAC” (n=6, 250 mg/kg of NAC introduced by nebulizer on alternate days on hyperoxia exposure), “control” (n=12, room air). Hyperoxia exposure resulted in enhanced production of reactive oxygen species (ROS) by bronchoalveolar lavage cells, 1,9-fold increased level of products reacting with thiobarbituric acid (TBARP), low glutathione peroxidase activity and glutathione (G-SH) in bronchoalveolar lavage fluid (BALF) (30% and 68% of controls respectively); elevated alpha1-antitrypsin (A1-AT), neutrophil elastase and matrix metalloproteases MMP2 and MMP9 in lung homogenates (141%, 286%, 132%, and 176% of controls respectively) (for all p<0,05 versus controls). In “hyperoxia+NAC” group, ROS generation was reduced as compared to group “hyperoxia” (1,9 times, p<0,05); glutathione peroxidase, G-SH, TBARP and elastase levels did not differ significantly from the group “control”, the activity of A1-AT was 3,8-fold higher than in controls (p<0,05), MMP2 and MMP9 levels remained elevated. Lung morphometry revealed normal proportion between alveolar spaces and septa area after NAC inhalations. Thus, inhaled NAC caused normalization of redox balance and improved elastase/A1-AT ratio in lungs of newborn guinea pigs exposed to prolonged hyperoxia.
Footnotes
Cite this article as: European Respiratory Journal 2018 52: Suppl. 62, PA1387.
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- Copyright ©the authors 2018