Perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (GenX): Hepatic stress and bile acid metabolism with different pathways

Hee Joon Yoo; Min Cheol Pyo; Kyu Hyun Rhee; Jae Min Lim; Seon Ah Yang; Min Ki Yoo; Kwang Won Lee

doi:10.1016/j.ecoenv.2023.115001

Perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (GenX): Hepatic stress and bile acid metabolism with different pathways

Hee Joon Yoo, Min Cheol Pyo, Kyu Hyun Rhee, Jae Min Lim, Seon Ah Yang, Min Ki Yoo, Kwang Won Lee

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

8 Citations (Scopus)

Abstract

Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms.

Original language	English
Article number	115001
Journal	Ecotoxicology and Environmental Safety
Volume	259
DOIs	https://doi.org/10.1016/j.ecoenv.2023.115001
Publication status	Published - 2023 Jul 1

Bibliographical note

Funding Information:
This work was supported by a Korea University grant ( K2109041 ). The authors thank the Institute of Biomedical Science & Food Safety, Korea University-CJ Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities.

Funding Information:
This work was supported by a Korea University grant (K2109041). The authors thank the Institute of Biomedical Science & Food Safety, Korea University-CJ Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities.

Publisher Copyright:
© 2023 The Authors

Keywords

GenX
Hepatotoxicity
Hexafluoropropylene oxide-dimer acid
Per- and polyfluoroalkyl substance
Perfluorooctanoic acid
PFOA

ASJC Scopus subject areas

Pollution
Public Health, Environmental and Occupational Health
Health, Toxicology and Mutagenesis

UN SDGs

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

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10.1016/j.ecoenv.2023.115001

Cite this

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title = "Perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (GenX): Hepatic stress and bile acid metabolism with different pathways",

abstract = "Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms.",

keywords = "GenX, Hepatotoxicity, Hexafluoropropylene oxide-dimer acid, Per- and polyfluoroalkyl substance, Perfluorooctanoic acid, PFOA",

author = "Yoo, {Hee Joon} and Pyo, {Min Cheol} and Rhee, {Kyu Hyun} and Lim, {Jae Min} and Yang, {Seon Ah} and Yoo, {Min Ki} and Lee, {Kwang Won}",

note = "Funding Information: This work was supported by a Korea University grant ( K2109041 ). The authors thank the Institute of Biomedical Science & Food Safety, Korea University-CJ Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities. Funding Information: This work was supported by a Korea University grant (K2109041). The authors thank the Institute of Biomedical Science & Food Safety, Korea University-CJ Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

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doi = "10.1016/j.ecoenv.2023.115001",

language = "English",

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AU - Yoo, Hee Joon

AU - Pyo, Min Cheol

AU - Rhee, Kyu Hyun

AU - Lim, Jae Min

AU - Yang, Seon Ah

AU - Yoo, Min Ki

AU - Lee, Kwang Won

N1 - Funding Information: This work was supported by a Korea University grant ( K2109041 ). The authors thank the Institute of Biomedical Science & Food Safety, Korea University-CJ Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities. Funding Information: This work was supported by a Korea University grant (K2109041). The authors thank the Institute of Biomedical Science & Food Safety, Korea University-CJ Food Safety Hall (Seoul, South Korea) for providing the equipment and facilities. Publisher Copyright: © 2023 The Authors

PY - 2023/7/1

Y1 - 2023/7/1

N2 - Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms.

AB - Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms.

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VL - 259

JO - Ecotoxicology and Environmental Safety

JF - Ecotoxicology and Environmental Safety

M1 - 115001

ER -

Perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (GenX): Hepatic stress and bile acid metabolism with different pathways

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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