Interaction of high temperature and NO2 exposure on asthma risk: In vivo experimental evidence of inflammation and oxidative stress

Abstract

Allergic asthma is a complicated respiratory disease with many concerns. Mounting epidemiological evidence linked temperature (T) and NO2 with allergic asthma, yet toxicological studies remain scarce. We conducted an in vivo study to explore toxicological evidence in T-NO2 interaction on allergic asthma, to investigate underlying toxicological mechanisms. 90 male Balb/c mice were randomly and equally divided into 6 groups including saline control, ovalbumin (OVA)-sensitized, OVA + 35 °C, OVA + NO2, OVA + 35 °C + NO2, and OVA + 35 °C + NO2 + capsazepine (CZP), adopting treatment for 38 days. We measured pulmonary functions of inspiratory resistance (Ri), expiratory resistance (Re) and airway compliance (Cldyn), serum protein biomarkers, indexes of pulmonary inflammation, histopathological changes and protective effects of CZP. Airway hyperresponsiveness (AHR) was aggravated by high T (35 °C) and NO2 (5 ppm) co-exposure with a series of aggravating asthmatic symptoms including airway wall thickening, lumen stenosis, goblet cell proliferation, mucus hypersecretion, and subepithelial fibrotic hyperplasia, providing evidence in the toxicological impact of high T-NO2 interaction. The biomarkers of serum immune functions (Total-IgE, OVA-sIgE and IL-4), pro-inflammation (IL-6 and TNF-α), oxidative stress cytokines (8-OHdG, ROS and MDA), airway resistance (Ri and Re), and TRPV1 expression significantly increased, while IFN-γ, GSH and airway compliance (Cldyn) significantly decreased with co-exposure to high T and NO2. We observed that CZP addition significantly ameliorated these toxicological effects and biomarker levels induced by heat-NO2 interaction. Our results suggest a toxicity of heat-NO2 interaction on asthma with clear mechanisms, which can be ameliorated by CZP, indicating that both oxidative stress and TRPV1 expression may be primarily responsible for asthma of heat-NO2-induced toxicity.