Identification of multiple dysregulated metabolic pathways by GC-MS-based profiling of lung tissue in mice with...

The risk of development of asthma, a multi-faceted chronic disease, increases as a result of exposure to PM_2.5. However, the mechanism underlying asthma-related metabolic changes caused by PM_2.5 exposure is unclear. Here, we investigated the major metabolic changes, metabolic pathways involved, and underlying molecular mechanisms in mice with PM_2.5 exposure-induced asthma. Forty-eight adult female mice were randomly assigned to control (C), low concentration-PM_2.5 exposure: 0.50 mg kg^-1 (L), medium concentration-PM_2.5 exposure: 1.58 mg kg^-1 (M), and high concentration-PM_2.5 exposure: 4.98 mg kg^-1 (H) groups. M and H groups presented significantly higher IL-4, IL-8, IL-1β, IL-5, IL-13, and OVA-specific IgE levels, and significantly lower IFN-γ levels, than the C group, as well as significantly increased eosinophil count and MUC5AC expression in the lung tissue. These findings indicate that exposure to medium and high concentrations of PM_2.5 induced asthma in mice. Statistical analyses identified 13 asthma-related major metabolites, which were analyzed by gas chromatography-mass spectrometry (GC-MS). Meta Mapp Software revealed 4 major metabolic pathways. PM_2.5-induced ATP requirement and oxidative stress may perturb metabolic processes in asthma. The present findings increase our understanding of the toxic effect of PM_2.5 in the development of asthma and identify potentially useful biomarkers.