Serum metabolomics analysis of mice that received repeated airway exposure to a water-soluble PM2.5 extract

Abstract

Background: Air pollutant exposure negatively affects human health; however, the molecular mechanisms causing disease remain largely unclear.

Objectives: To explore the effects of respiratory particulate matter (PM2.5) exposure on the serum metabolome and to identify biomarkers for risk assessment of PM2.5 exposure.

Methods: PM2.5 from Nanjing, China, was collected, and its water-soluble extract was subjected to component analysis. BALB/c mice received acute or prolonged exposure to insoluble PM2.5 particles or its water-soluble extract, and lung tissue was submitted to histopathological analyses. Serum samples were collected pre- and post-PM2.5 exposure and analyzed by liquid chromatography/mass spectrometry.

Results: Component analysis revealed that metals and inorganic ions were the most abundant components in the soluble PM2.5 samples. Acute exposure to insoluble PM2.5 particles and prolonged exposure to the water-soluble PM2.5 extract both induced severe lung injury, and the lung histopathological scores were significantly associated with PM2.5 exposure. Metabolomics analysis showed that prolonged exposure to the water-soluble PM2.5 extract was associated with statistically significant metabolite changes; the serum concentrations of 30 known metabolites, including metabolites of phospholipids, amino acids and sphingolipids, differed significantly between the control and PM2.5 exposure group. Pathway analysis identified an association of the tricarboxylic acid cycle (TCA) and the phospholipase metabolism pathway with PM2.5 exposure. The most influential metabolites for discriminating between the PM2.5-exposure group serum and the control serum were LysoPE, LysoPC, LGPC, citric acid, PAF C-18, NeuAcalpha2-3Galbeta-Cer, Lyso-PAF C-16, ganglioside GA2, 1-sn-glycero-3-phosphocholine, PC and L-tryptophan.

Conclusions: Respiratory exposure to water-soluble PM2.5 extract has developmental consequences affecting not only the respiratory system but also metabolism.

Keywords: Lung; Metabolomics; PM2.5; Serum.