Impact of perfluoroalkyl substances (PFAS) and PFAS mixtures on lipid metabolism in differentiated HepaRG cells as a model for human hepatocytes

• DOI: 10.1007/s00204-023-03649-3
• Publication Date: 2023-12-20T13:02:18Z
• Authors: Faezeh Sadrabadi; Jimmy Alarcan; Heike Sprenger; Albert Braeuning; Thorsten Buhrke
• Keywords: Steatosis

Abstract Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants with various adverse health effects in humans including disruption of lipid metabolism. Aim the present study was to elucidate molecular mechanisms PFAS-mediated on metabolism human cells. Here, we examined impact a number PFAS (PFOS, PFOA, PFNA, PFDA, PFHxA, PFBA, PFHxS, PFBS, HFPO-DA, PMPP) some exposure-relevant mixtures being composed PFOS, PFNA PFHxS HepaRG cells, an vitro model for hepatocytes. At near cytotoxic concentrations, selected induced triglyceride accumulation cells consistently affected expression marker genes steatosis, as well PPARα target related cholesterol metabolism, pointing common disrupting cellular homeostasis. activation by transactivation assay HEK293T synergistic were observed at sum concentrations higher than 25 µM, whereas additivity lower µM. Of note, any effect assays occurred that least four five magnitudes above real-life internal exposure levels general population.