Particulate Metal Exposures Induce Plasma Metabolome Changes in a Commuter Panel Study
| Autor: | Rachel Golan, W. Dana Flanders, Jeremy A. Sarnat, Tianwei Yu, Gary W. Miller, Dean P. Jones, Karan Uppal, Donghai Liang, Chandresh Ladva, ViLinh Tran, Roby Greenwald, Douglas I Walker, Amit U. Raysoni |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Metabolite Air pollution lcsh:Medicine Inflammation 010501 environmental sciences Pharmacology medicine.disease_cause 01 natural sciences Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Human health Metabolomics Metabolome medicine Humans lcsh:Science Vehicle Emissions 0105 earth and related environmental sciences General Environmental Science Particulate metal Leukotriene Cross-Over Studies Smog Multidisciplinary lcsh:R Environmental Exposure Metabolism Metabolic pathway C-Reactive Protein 030104 developmental biology chemistry Metals Environmental chemistry Cytokines General Earth and Planetary Sciences Environmental science Female lcsh:Q Inflammation Mediators medicine.symptom Biomarkers |
| Zdroj: | PLoS ONE, Vol 13, Iss 9, p e0203468 (2018) |
| ISSN: | 1078-0475 |
| DOI: | 10.1289/isesisee.2018.o01.03.62 |
| Popis: | Introduction 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. Methods 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. Results 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. Conclusions Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation. |
| Databáze: | OpenAIRE |
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