Effect of NO 2 exposure on airway inflammation and oxidative stress in asthmatic mice.

Nitrogen dioxide (NO ₂ ) is a widespread air pollutant. Epidemiological evidence indicates that NO ₂ is associated with an increase of incidence rate and mortality of asthma, but its mechanism is still unclear. In this study, we exposed mice to NO ₂ (5 ppm, 4 h per day for 30 days) intermittently to investigate the development and potential toxicological mechanisms of allergic asthma. We randomly assigned 60 male Balb/c mice to four groups: saline control, ovalbumin (OVA) sensitization, NO ₂ alone, and OVA+NO ₂ groups. The involved mechanisms were found from the perspective of airway inflammation and oxidative stress. The results showed that NO ₂ exposure could aggravate lung inflammation in asthmatic mice, and airway remodeling was characterized by significant thickening of the airway wall and infiltration of inflammatory cells. Moreover, NO ₂ would aggravate the airway hyperresponsiveness (AHR), which is characterized by significantly elevated inspiratory resistance (Ri) and expiratory resistance (Re), as well as decreased dynamic lung compliance (Cldyn). In addition, NO ₂ exposure promoted pro-inflammatory cytokines (IL-6 and TNF-α) and serum immunoglobulin (IgE) production. The imbalance of Th1/Th2 cell differentiation (IL-4 increased, IFN-γ reduced, IL-4/IFN-γ significantly increased) played a key role in the inflammatory response of asthma under NO ₂ exposure. In a nutshell, NO ₂ exposure could promote allergic airway inflammation and increase asthma susceptibility. The levels of ROS and MDA among asthmatic mice exposed to NO ₂ increased significantly, while GSH levels sharply decreased. These findings may provide better toxicological evidence for the mechanisms of allergic asthma risk due to NO ₂ exposure.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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