ArticleArchives of toxicology2020
Impairment of bile acid metabolism by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in human HepaRG hepatoma cells.
Article in Archives of toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- A metabolomic investigation of serum perfluorooctane sulfonate and perfluorooctanoate.Environment international · 2023Pooled it
- Perfluorooctane sulfonate (PFOS) interferes with Cyp1a activity and dysregulates the aryl hydrocarbon receptor pathway in larval zebrafish (Danio rerio).Environmental pollution (Barking, Essex : 1987) · 2026Article
- Analysis of transcriptomic alterations induced by 33 different per- and polyfluoroalkyl substances (PFAS) in differentiated HepaRG cells.Archives of toxicology · 2026Article
- Perfluorooctanoic Acid (PFOA) Alters the Structure of the Gut Microbial Community and Colonoid Transcription.Current issues in molecular biology · 2026Article
- Toxicological Effects and Health Impacts of Per- and Polyfluoroalkyl Substances (PFAS) in Humans.Toxics · 2026Review
- Perfluorooctane Sulfonate (PFOS) Disrupts Mitochondrial Activity and Cell Adhesion in Liver Cells.Journal of xenobiotics · 2026Article
- PFOS-induced black liver and hepatic aging in mice: A new paradigm in environmental hepatotoxicology.Environment international · 2026Article
- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Investigation of the toxicological effects of PFAS on cholangiocarcinoma based on network toxicology, bioinformatics, and molecular docking.Scientific reports · 2025Article
- Identification of four mechanisms of toxicity for per- and polyfluoroalkyl substances through transcriptomic profiling in human liver spheroids exposed to 24 PFAS.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Molecular Shadows of Per- and Polyfluoroalkyl Substances (PFASs): Unveiling the Impact of Perfluoroalkyl Substances on Ovarian Function, Polycystic Ovarian Syndrome (PCOS), and In Vitro Fertilization (IVF) Outcomes.International journal of molecular sciences · 2025Review
- High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy.The Science of the total environment · 2025Article
- Circulating per- and polyfluoroalkyl substances and liver cancer risk: a nested case-control analysis of individual participant data from 12 prospective cohorts.Environmental health perspectives · 2025Article
- PFC/PFAS concentrations in human milk and infant exposure through lactation: a comprehensive review of the scientific literature.Archives of toxicology · 2025Review
- Early pregnancy serum PFAS are associated with alterations in the maternal lipidome.Environmental research · 2024Article
- Identification of Plant Peroxidases Catalyzing the Degradation of Fluorinated Aromatics Using a Peroxidase Library Approach.Engineering in life sciences · 2024Article
- In vitro screening of understudied PFAS with a focus on lipid metabolism disruption.Archives of toxicology · 2024Article
- Exposure ofEnvironmental health perspectives · 2024Article
- Effects of PFAS on human liver transporters: implications for health outcomes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Involvement of per- and polyfluoroalkyl compounds in tumor development.Archives of toxicology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are man-made chemicals that are used for the fabrication of many products with water- and dirt-repellent properties. The toxicological potential of both substances is currently under debate. In a recent Scientific Opinion, the European Food Safety Authority (EFSA) has identified increased serum total cholesterol levels in humans as one major critical effect being associated with exposure to PFOA or PFOS. In animal studies, both substances induced a decrease of serum cholesterol levels, and the underlying molecular mechanism(s) for these opposed effects are unclear so far. In the present study, we examined the impact of PFOA and PFOS on cholesterol homoeostasis in the human HepaRG cell line as a model for human hepatocytes. Cholesterol levels in HepaRG cells were not affected by PFOA or PFOS, but both substances strongly decreased synthesis of a number of bile acids. The expression of numerous genes whose products are involved in synthesis, metabolism and transport of cholesterol and bile acids was strongly affected by PFOA and PFOS at concentrations above 10 µM. Notably, both substances led to a strong decrease of CYP7A1, the key enzyme catalyzing the rate-limiting step in the synthesis of bile acids from cholesterol, both at the protein level and at the level of gene expression. Moreover, both substances led to a dilatation of bile canaliculi that are formed by differentiated HepaRG cells in vitro. Similar morphological changes are known to be induced by cholestatic agents in vivo. Thus, the strong impact of PFOA and PFOS on bile acid synthesis and bile canalicular morphology in our in vitro experiments may allow the notion that both substances have a cholestatic potential that is connected to the observed increased serum cholesterol levels in humans in epidemiological studies.
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Registered trials
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