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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

PLoS One. 2018 ;13(9):e0203468. Epub 2018 Sep 19. PMID: 30231074

Abstract Author(s):

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

Article Affiliation:

Chandresh Nanji Ladva

Abstract:

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.

Study Type : Human Study

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Sayer Ji
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