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Title: Particulate metal exposures induce plasma metabolome changes in a commuter panel study.

Authors: Ladva, Chandresh Nanji; Golan, Rachel; Liang, Donghai; Greenwald, Roby; Walker, Douglas I; Uppal, Karan; Raysoni, Amit U; Tran, ViLinh; Yu, Tianwei; Flanders, W Dana; Miller, Gary W; Jones, Dean P; Sarnat, Jeremy A

Published In PLoS One, (2018)

Abstract: Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures.A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog.HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response.Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.

PubMed ID: 30231074 Exiting the NIEHS site

MeSH Terms: Adult; Biomarkers/blood; C-Reactive Protein/metabolism*; Cross-Over Studies; Cytokines/blood*; Environmental Exposure/adverse effects*; Female; Humans; Inflammation Mediators/blood*; Male; Metabolome*; Metals/toxicity*; Smog/adverse effects*; Vehicle Emissions*

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