Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice

Pan Deng; Chunyan Wang; Banrida Wahlang; Travis Sexton; Andrew J. Morris; Bernhard Hennig

doi:10.1016/j.taap.2020.115301

Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice

Pan Deng
, Chunyan Wang
, Banrida Wahlang
, Travis Sexton
, Andrew J. Morris
, Bernhard Hennig

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.

Original language	English
Article number	115301
Journal	Toxicology and Applied Pharmacology
Volume	409
DOIs	https://doi.org/10.1016/j.taap.2020.115301
State	Published - Dec 15 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Funding

We thank Dr. Hunter N.B. Moseley (Institute for Biomedical Informatics, University of Kentucky) for helpful discussions. The current study is supported by the NIEHS/NIH grant P42ES007380 and T32ES011564, and NIGMS/NIH grant P30 GM127211 and 1S10OD021753-01A1. We thank Dr. Hunter N.B. Moseley (Institute for Biomedical Informatics, University of Kentucky) for helpful discussions. The current study is supported by the NIEHS /NIH grant P42ES007380 and T32ES011564 , and NIGMS / NIH grant P30 GM127211 and 1S10OD021753-01A1 .

Funders	Funder number
NIH-NIEHS-SRC
NIH/NIGMS
National Institutes of Health (NIH)
NIH Office of the Director	S10OD021753
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	P30 GM127211
National Institutes of Health/National Institute of Environmental Health Sciences	T32ES011564, P42ES007380

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cardiovascular disease
Lipid
Liver
PCB126
PFAS
PFOS

ASJC Scopus subject areas

Toxicology
Pharmacology

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10.1016/j.taap.2020.115301

Cite this

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title = "Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice",

abstract = "Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.",

keywords = "Cardiovascular disease, Lipid, Liver, PCB126, PFAS, PFOS",

author = "Pan Deng and Chunyan Wang and Banrida Wahlang and Travis Sexton and Morris, \{Andrew J.\} and Bernhard Hennig",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = dec,

day = "15",

doi = "10.1016/j.taap.2020.115301",

language = "English",

volume = "409",

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T1 - Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice

AU - Deng, Pan

AU - Wang, Chunyan

AU - Wahlang, Banrida

AU - Sexton, Travis

AU - Morris, Andrew J.

AU - Hennig, Bernhard

PY - 2020/12/15

Y1 - 2020/12/15

N2 - Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.

AB - Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.

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KW - Lipid

KW - Liver

KW - PCB126

KW - PFAS

KW - PFOS

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Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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