Perfluoroalkyl substances (PFASs) are substrates of the renal human organic anion transporter 4 (OAT4).

Autor: Louisse J; Wageningen Food Safety Research, Wageningen University and Research, Wageningen, The Netherlands. jochem.louisse@wur.nl., Dellafiora L; Department of Food and Drug, University of Parma, 43124, Parma, Italy., van den Heuvel JJMW; Department of Pharmacology and Toxicology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands., Rijkers D; Wageningen Food Safety Research, Wageningen University and Research, Wageningen, The Netherlands., Leenders L; Wageningen Food Safety Research, Wageningen University and Research, Wageningen, The Netherlands., Dorne JCM; Methodological and Scientific Support Unit, European Food Safety Authority, Via Carlo Magno 1A, 43124, Parma, Italy., Punt A; Wageningen Food Safety Research, Wageningen University and Research, Wageningen, The Netherlands., Russel FGM; Department of Pharmacology and Toxicology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands., Koenderink JB; Department of Pharmacology and Toxicology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2023 Mar; Vol. 97 (3), pp. 685-696. Date of Electronic Publication: 2022 Nov 27.
DOI: 10.1007/s00204-022-03428-6
Abstrakt: Poly- and perfluoroalkyl substances (PFASs) are omnipresent in the environment and have been shown to accumulate in humans. Most PFASs are not biotransformed in animals and humans, so that elimination is largely dependent on non-metabolic clearance via bile and urine. Accumulation of certain PFASs in humans may relate to their reabsorption from the pre-urine by transporter proteins in the proximal tubules of the kidney, such as URAT1 and OAT4. The present study assessed the in vitro transport of 7 PFASs (PFHpA, PFOA, PFNA, PFDA, PFBS, PFHxS and PFOS) applying URAT1- or OAT4-transfected human embryonic kidney (HEK) cells. Virtually no transport of PFASs could be measured in URAT1-transfected HEK cells. All PFASs, except PFBS, showed clear uptake in OAT4-transfected HEK cells. In addition, these in vitro results were further supported by in silico docking and molecular dynamic simulation studies assessing transporter-ligand interactions. Information on OAT4-mediated transport may provide insight into the accumulation potential of PFASs in humans, but other kinetic aspects may play a role and should also be taken into account. Quantitative information on all relevant kinetic processes should be integrated in physiologically based kinetic (PBK) models, to predict congener-specific accumulation of PFASs in humans in a more accurate manner.
(© 2022. The Author(s).)
Databáze: MEDLINE
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