Impact of perfluoroalkyl substances (PFAS) and PFAS mixtures on lipid metabolism in differentiated HepaRG cells as a model for human hepatocytes.
Arch Toxicol
; 98(2): 507-524, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38117326
ABSTRACT
Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants with various adverse health effects in humans including disruption of lipid metabolism. Aim of the present study was to elucidate the molecular mechanisms of PFAS-mediated effects on lipid metabolism in human cells. Here, we examined the impact of a number of PFAS (PFOS, PFOA, PFNA, PFDA, PFHxA, PFBA, PFHxS, PFBS, HFPO-DA, and PMPP) and of some exposure-relevant PFAS mixtures being composed of PFOS, PFOA, PFNA and PFHxS on lipid metabolism in human HepaRG cells, an in vitro model for human hepatocytes. At near cytotoxic concentrations, the selected PFAS and PFAS mixtures induced triglyceride accumulation in HepaRG cells and consistently affected the expression of marker genes for steatosis, as well as PPARα target genes and genes related to lipid and cholesterol metabolism, pointing to common molecular mechanisms of PFAS in disrupting cellular lipid and cholesterol homeostasis. PPARα activation was examined by a transactivation assay in HEK293T cells, and synergistic effects were observed for the selected PFAS mixtures at sum concentrations higher than 25 µM, whereas additivity was observed at sum concentrations lower than 25 µM. Of note, any effect observed in the in vitro assays occurred at PFAS concentrations that were at least four to five magnitudes above real-life internal exposure levels of the general population.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Alcanossulfônicos
/
Poluentes Ambientais
/
Fluorocarbonos
Limite:
Humans
Idioma:
En
Revista:
Arch Toxicol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha