Urban air inhalation exacerbates the oxinflammatory response after an acute lung injury, hindering alveolar epithelium repair

REYNOSO, SOFIA; FLORENCIA SARNO; CALTANA LAURA; FREIRE, AGUSTINA; MARIANA GARCES; CACERES LOURDES; MARCHINI TIMOTEO; EVELSON PABLO; MAGNANI NATALIA

Congreso; SFRBM 23 Uruguay; 2023

Breathing air pollution is a worldwide leading cause of deleterioushealth effects. Mainly airborne particulate matter (PM) byinitiating oxidative stress and inflammatory pathways contribute tothe initiation and aggravation of respiratory diseases. We aimed tostudy the PM-induced oxiinflammation mechanisms associatedwith a delayed repair of an acute lung injury. BALB/c mice wereexposed to filtered air (FA) or urban air from Buenos Aires City(UA), in whole-body exposure chambers for 8 weeks. Then, anacute lung injury was induced by intratracheal instillation of 0.1 Nhydrochloric acid (HCl). Samples were evaluated 5 days afterinjury. The reactive oxygen species (ROS) production wasincreased by UA exposure after lung injury, as NADPH oxidaseactivity and mitochondrial H2O2 production were augmented(p≤0.05). When redox-sensitive transcription factors wereevaluated, we observed that although Nrf2 expression was higherin the UA+HCl group (p≤0.05) compared to control values, theOH-1 expression did not change, and the antioxidant system wasimpaired. Regarding NF-κB, after lung injury, mice breathing UApresented increased p65 subunit translocation to the nuclei(p≤0.05), which may be responsible for the altered inflammatoryresponse observed as TNF-α levels were increased (p≤0.001),together with elevated total cell count and protein concentration inBAL samples from UA-exposed mice (p≤0.001 and p≤0.01respectably). Furthermore, UA triggered alveolar septal thickening(p≤0.0001) after injury, due to impaired alveolo-capillary barrierdamage, that could be explained by the increased oxidative damageto lipids evaluated by 4-HNE expression (p≤0.05). Taken together,these results showed that when PM reach the lung promotes a shiftto a more oxidant redox status, leading to oxidative tissue damagealong with an exacerbated inflammatory response. As a result,mice exposed to UA were not able to properly repair the alveolarepithelium injury, resulting in a slower recovery from an acutelung injury.