Cited by 235Per- and polyfluoroalkyl substances researchPeroxisome Proliferator-Activated ReceptorsFluorine in Organic Chemistry

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.

Activation of human nuclear receptors by perfluoroalkylated substances (PFAS)

Abstract

Perfluoralkylated substances (PFAS) such as perfluorooctanoic acid (PFOA) or perfluorooctanesulfonic acid (PFOS) are used to produce, e.g., surface coatings with water- and dirt-repellent properties. These substances have been shown to be hepatotoxic in rodents, and the mechanism of action is mostly attributed to the PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). In the present study, we investigated by using luciferase-based reporter gene assays whether PFOA, PFOS and six alternative PFAS can activate, in addition to PPARα, eight other human nuclear receptors. All tested PFAS except for perfluorobutanesulfonic acid (PFBS) were able to activate human PPARα. Perfluoro-2-methyl-3-oxahexanoic acid (PMOH) and 3H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP) were weak agonists of human PPARγ. The other human nuclear receptors (PPARδ, CAR, PXR, FXR, LXRα, RXRα and RARα) were not affected by any PFAS tested in this study. Although PMOH was more effective than PFOA in stimulating PPARα in the transactivation assay, it was less effective in stimulating PPARα-dependent target gene expression in human HepG2 hepatocarcinoma cells. Notably, any effect observed in this in vitro study only occurred at concentrations higher than 10 μM of the respective PFAS which is in all cases several magnitudes above the average blood concentration in the Western population. Thus, the results suggest that nuclear receptor activation may only play a minor role in potential PFAS-mediated adverse effects in humans.

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Crossref · 10.1016/j.tiv.2019.104700

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Metadata

Authors
Behr, A.-C., Plinsch, C., Braeuning, A., & Buhrke, T.
Affiliations
German Federal Institute for Risk Assessment (BfR) (DE)
Corresponding author
Buhrke, Thorsten
Venue
Toxicology in Vitro
Publisher
Elsevier BV
Published
2020-02
Volume
62
Pages
104700
ISSN
0887-2333 (ISSN-L)
OpenAlex
W2982329931
Cited by
235
References
53
Citations by year
2026: 36 · 2025: 41 · 2024: 32 · 2023: 40 · 2022: 43 · 2021: 32 · 2020: 11
FWCI
9.36
Type
journal article
Language
en
Open access
closed
Locations
  • Toxicology in Vitro (publishedVersion)
  • PubMed (publishedVersion)
  • OpenAgrar (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Physical Sciences › Chemistry › Organic Chemistry › Fluorine in Organic Chemistry
Keywords
perfluorooctanoic acid, PFOS, PFBS, PPARα, PPARγ, nuclear receptor activation, hepatotoxicity, PPARα agonist, PFAS alternatives, HepG2 cells, endocrine disruption
MeSH terms
Caprylates, Fluorocarbons, Humans, Sulfonic Acids, Transcriptional Activation, Gene Expression, Alkanesulfonic Acids, Genes, Reporter, Receptors, Cytoplasmic and Nuclear, Cell Line, Tumor, PPAR alpha, Hep G2 Cells, HEK293 Cells

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