The Oxidative Potential of Fine Particulate Matter and Biological Perturbations in Human Plasma and Saliva Metabolome Pubblico

Abstract

Background: Exposure assessment and health impact evaluation of particulate matter (PM) mixtures remain very challenging. Fine particle oxidative potential (FPMOP) has been considered as a key health-relevant particulate parameter. We measured FPMOP exposures in a recent panel study and corresponding metabolic perturbations to evaluate its potential epidemiologic value and examine molecular mechanisms underlying PM-related health impacts.

Methods: We recruited 54 participants from two dormitories in Atlanta, GA near and far from a congested highway. Indoor or outdoor FPMOP levels at the dormitories were measured using dithiothreitol (DTT) assay. Plasma and saliva samples were collected from participants at four time points during 12 weeks. Liquid chromatography coupled with high-resolution mass spectrometry was used to profile the participants’ metabolome. We used mixed effect models to examine associations between metabolic features and FPMOP, controlling for potential confounders including age, gender, race, and body mass index. Significant metabolic features meeting false positive discovery rate at 20% were used for pathway enrichment analysis and metabolite annotation.

Results: The 96h-mean water soluble FPMOP levels at the near and far dormitories prior to biosample collection were 26.3 and 22.9 nmol/min/μg, respectively. In total, we extracted 20,766 metabolic features from plasma samples and 29,013 from saliva samples. Purine metabolism, N- glycan biosynthesis, and beta-alanine metabolism were most strongly associated with 5 or more FPMOP-related measurements in plasma, while vitamin E metabolism, leukotriene metabolism, and glycosphingolipid metabolism were found associated with FPMOP in saliva. We confirmed 6 metabolites directly associated with FPMOP measurements with level 1 evidence, including hypoxanthine, histidine, pyruvate, lactate/glyceraldehyde, azelaic acid, and petroselinic acid/elaidic acid/oleate, which were implications of perturbations in amino acid, carbohydrate, nucleotide and lipid metabolism.

Conclusions: We identified metabolites and pathways perturbations in plasma and saliva following by higher FPMOP exposure in panel-based setting. Perturbations in amino acid, carbohydrate, nucleotide and lipid metabolism may elicit PM-related health impacts. 

Table of Contents

Introduction..........................................................................................................................1

Methods............................................................................................................................... 3

Exposure assessment on FPMOP............................................................................................. 3

Panel study participant recruitment. ...................................................................................... 4

High-resolution metabolomics profiling.................................................................................. 5

Data analysis .........................................................................................................................6

Pathway enrichment analysis and metabolite annotation. .................................................... ....7

Results. .................................................................................................................................8

Discussion.............................................................................................................................11

Conclusions...........................................................................................................................17

References. ........................................................................................................................... 19

Tables and Figures................................................................................................................. 27

Supplementary Tables and Figures........................................................................................... 41 

About this Master's Thesis

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School	Rollins School of Public Health
Department	Environmental Health
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Environmental Health
Parola chiave	Dithiothreitol Assay High Resolution Metabolomics Fine Particulate Matter Oxidative Potential
Committee Chair / Thesis Advisor	Liang, Donghai, Emory University

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