Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone

Air pollution exposure, especially particulate matter (PM) and ozone (O3), poses significant health risks, but the systemic metabolic consequences of combined exposures to PM and O3, remain poorly understood. This study investigated systemic metabolic changes in male spontaneously hypertensive (SH)...

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Main Authors: Yue Ge, Maliha S. Nash, Aimen K. Farraj
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Research in Toxicology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666027X25000027
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author Yue Ge
Maliha S. Nash
Aimen K. Farraj
author_facet Yue Ge
Maliha S. Nash
Aimen K. Farraj
author_sort Yue Ge
collection DOAJ
description Air pollution exposure, especially particulate matter (PM) and ozone (O3), poses significant health risks, but the systemic metabolic consequences of combined exposures to PM and O3, remain poorly understood. This study investigated systemic metabolic changes in male spontaneously hypertensive (SH) rats following inhalation exposure to concentrated ambient particles (CAPs) (PM2.5, 150 μg/m3), ozone (O3) (0.2 ppm), and their combination. Rats were exposed for 4 h, and serum samples were collected 1-hour post-exposure. Using targeted metabolomics, we identified significant alterations in metabolites involved in lipid metabolism (phosphatidylcholines), energy metabolism (acylcarnitine C3), and oxidative stress (glutamine). Notably, the combination exposure induced distinct metabolic changes, including increased acylcarnitine C3 levels, suggesting heightened mitochondrial dysfunction. Principal component analysis revealed overlapping profiles between CAPs and controls, indicating a subtler impact of CAPs compared to ozone or combined exposure. These systemic metabolic alterations are aligned with our previously published proteomics findings in cardiac tissues from the same rats, which showed elevated inflammatory markers (e.g., IL-6, TNF-α) and mitochondrial dysfunction. In conclusion, this study provides new insights into the systemic metabolic effects of air pollutant exposure, identifies novel metabolic targets of pollutant-induced toxicity, highlights the complex interactions resulting from combined exposure to multiple pollutants, and underscores the importance of assessing the combined effects of multiple pollutants in air pollution risk assessments.
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spelling doaj-art-21a2a66de81a42cdaac17b3792b55c9e2025-01-24T04:45:41ZengElsevierCurrent Research in Toxicology2666-027X2025-01-018100216Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozoneYue Ge0Maliha S. Nash1Aimen K. Farraj2The Center for Computational Toxicology and Exposure, US Environmental Protection Agency, RTP, NC 27711, United States; Corresponding author.Center for Public Health and Environmental Assessment, US Environmental Protection Agency, RTP, NC 27711, United StatesCenter for Public Health and Environmental Assessment, US Environmental Protection Agency, RTP, NC 27711, United StatesAir pollution exposure, especially particulate matter (PM) and ozone (O3), poses significant health risks, but the systemic metabolic consequences of combined exposures to PM and O3, remain poorly understood. This study investigated systemic metabolic changes in male spontaneously hypertensive (SH) rats following inhalation exposure to concentrated ambient particles (CAPs) (PM2.5, 150 μg/m3), ozone (O3) (0.2 ppm), and their combination. Rats were exposed for 4 h, and serum samples were collected 1-hour post-exposure. Using targeted metabolomics, we identified significant alterations in metabolites involved in lipid metabolism (phosphatidylcholines), energy metabolism (acylcarnitine C3), and oxidative stress (glutamine). Notably, the combination exposure induced distinct metabolic changes, including increased acylcarnitine C3 levels, suggesting heightened mitochondrial dysfunction. Principal component analysis revealed overlapping profiles between CAPs and controls, indicating a subtler impact of CAPs compared to ozone or combined exposure. These systemic metabolic alterations are aligned with our previously published proteomics findings in cardiac tissues from the same rats, which showed elevated inflammatory markers (e.g., IL-6, TNF-α) and mitochondrial dysfunction. In conclusion, this study provides new insights into the systemic metabolic effects of air pollutant exposure, identifies novel metabolic targets of pollutant-induced toxicity, highlights the complex interactions resulting from combined exposure to multiple pollutants, and underscores the importance of assessing the combined effects of multiple pollutants in air pollution risk assessments.http://www.sciencedirect.com/science/article/pii/S2666027X25000027Particulate matter (PM)Ozone (O3)SerumMetabolismMetabolomicsProteomics
spellingShingle Yue Ge
Maliha S. Nash
Aimen K. Farraj
Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
Current Research in Toxicology
Particulate matter (PM)
Ozone (O3)
Serum
Metabolism
Metabolomics
Proteomics
title Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
title_full Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
title_fullStr Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
title_full_unstemmed Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
title_short Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
title_sort metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone
topic Particulate matter (PM)
Ozone (O3)
Serum
Metabolism
Metabolomics
Proteomics
url http://www.sciencedirect.com/science/article/pii/S2666027X25000027
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AT malihasnash metabolomicprofilingrevealssystemicmetabolicdisruptionsinducedbycombinedexposuretoparticulatematterandozone
AT aimenkfarraj metabolomicprofilingrevealssystemicmetabolicdisruptionsinducedbycombinedexposuretoparticulatematterandozone