Perfluoroalkyl substances (PFASs) are substrates of the renal human organic anion transporter 4 (OAT4)
| Autor: | Jochem Louisse, Luca Dellafiora, Jeroen J. M. W. van den Heuvel, Deborah Rijkers, Liz Leenders, Jean-Lou C. M. Dorne, Ans Punt, Frans G. M. Russel, Jan B. Koenderink |
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| Rok vydání: | 2023 |
| Předmět: |
Team Organic Contaminants
Health Toxicology and Mutagenesis lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Team Toxicology General Medicine Transporter Toxicology OAT4 All institutes and research themes of the Radboud University Medical Center Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] In vitro PFASs Renal reabsorption URAT1 |
| Zdroj: | Archives of Toxicology, 97, 3, pp. 685-696 Archives of Toxicology 97 (2023) 3 Archives of Toxicology, 97(3), 685-696 Archives of Toxicology, 97, 685-696 |
| ISSN: | 0340-5761 |
| Popis: | Contains fulltext : 291310.pdf (Publisher’s version ) (Open Access) 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. |
| Databáze: | OpenAIRE |
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