Identification of multiple dysregulated metabolic pathways by GC-MS-based profiling of liver tissue in mice with OVA-induced asthma exposed to PM2.5.

Particulate matter (PM) exposure increases the risk of asthma. However, the effect of PM2.5 exposure on liver metabolism in mice with asthma symptoms remains unclear. We established an ovalbumin (OVA)-induced asthma model in mice and divided the animals into four groups: control group (C), PM2.5 exposure group (P), OVA-induced asthma group (O) and OVA-induced asthma PM2.5 exposure group (OP). Gas chromatography-mass spectrometry (GC-MS) was used to identify the metabolite markers and related perturbed metabolic pathways in mouse liver tissue after PM2.5 exposure. Multivariate analysis showed 9 and 12 potential metabolite markers in the P and OP groups, respectively, after PM2.5 exposure that were significantly correlated with lipid peroxidation indices. PM2.5 exposure perturbed 5 and 7 metabolic pathways in the P and OP groups, respectively. These metabolic pathways mainly involve the lipid metabolism, amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism. These results highlight the potential to study PM2.5-triggered alterations via liver tissue in normal and OVA-induced asthmatic mice to gain a more realistic appraisal of the resulting early toxicity events. Additionally, these results revealed potential metabolite markers of early antioxidant defense events triggered by PM2.5 and indicated that metabolite markers are more sensitive than antioxidant indicators.

Identification of multiple dysregulated metabolic pathways by GC-MS-based profiling of lung tissue in mice with PM2.5-induced asthma.

The risk of development of asthma, a multi-faceted chronic disease, increases as a result of exposure to PM2.5. However, the mechanism underlying asthma-related metabolic changes caused by PM2.5 exposure is unclear. Here, we investigated the major metabolic changes, metabolic pathways involved, and underlying molecular mechanisms in mice with PM2.5 exposure-induced asthma. Forty-eight adult female mice were randomly assigned to control (C), low concentration-PM2.5 exposure: 0.50 mg kg-1 (L), medium concentration-PM2.5 exposure: 1.58 mg kg-1 (M), and high concentration-PM2.5 exposure: 4.98 mg kg-1 (H) groups. M and H groups presented significantly higher IL-4, IL-8, IL-1ß, 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 PM2.5 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. PM2.5-induced ATP requirement and oxidative stress may perturb metabolic processes in asthma. The present findings increase our understanding of the toxic effect of PM2.5 in the development of asthma and identify potentially useful biomarkers.