ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Mechanism of polybrominated diphenyl ether uptake into the liver: PBDE congeners are substrates of human hepatic OATP transporters.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 45 citations in OpenAlex.
- Distribution of polybrominated diphenyl ethers (PBDEs) in placental tissues of maternal and fetal origin in exposed Wistar rats and associations with thyroid hormone levels.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Investigating the interactions of flavonoids with human OATP2B1: inhibition assay, ICRSC medicinal chemistry · 2023Article
- Maternal transfer of environmentally relevant polybrominated diphenyl ethers (PBDEs) produces a diabetic phenotype and disrupts glucoregulatory hormones and hepatic endocannabinoids in adult mouse female offspring.Scientific reports · 2020Article
- PBDEs Concentrate in the Fetal Portion of the Placenta: Implications for Thyroid Hormone Dysregulation.Endocrinology · 2019Article
- Hepatic Transport of 25-Hydroxyvitamin DDrug metabolism and disposition: the biological fate of chemicals · 2018Article
- Hepatic Uptake Mechanism of Ophiopogonin D Mediated by Organic Anion Transporting Polypeptides.European journal of drug metabolism and pharmacokinetics · 2017Article
- Organic Anion Transporting Polypeptides Contribute to the Disposition of Perfluoroalkyl Acids in Humans and Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Do flame retardant chemicals increase the risk for thyroid dysregulation and cancer?Current opinion in oncology · 2017Review
- Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints.Environmental health : a global access science source · 2016Article
- Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP).Toxicology and applied pharmacology · 2016Article
- Estimation of tetrabromobisphenol A (TBBPA) percutaneous uptake in humans using the parallelogram method.Toxicology and applied pharmacology · 2015Article
- OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies.British journal of pharmacology · 2012Review
- Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice.Toxicology and applied pharmacology · 2011Article
- Interactions of green tea catechins with organic anion-transporting polypeptides.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Scientific Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food.EFSA journal. European Food Safety Authority · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Polybrominated diphenyl ethers (PBDEs) are flame-retardants that upon chronic exposure enter the liver where they are biotransformed to potentially toxic metabolites. The mechanism by which PBDEs enter the liver is not known. However, due to their large molecular weights (MWs approximately 485 to 1000 Da), they cannot enter hepatocytes by simple diffusion. Organic anion-transporting polypeptides (OATPs) are responsible for hepatic uptake of a variety of amphipathic compounds of MWs larger than 350 Da. Therefore, in the present study, Chinese hamster ovary cell lines expressing OATP1B1, OATP1B3, and OATP2B1 were used to test the hypothesis that OATPs expressed in human hepatocytes would be responsible for the uptake of PBDE congeners 47, 99, and 153. The results demonstrated that PBDE congeners inhibited OATP1B1- and OATP1B3-mediated uptake of estradiol-17-beta-glucuronide as well as OATP2B1-mediated uptake of estrone-3-sulfate in a concentration-dependent manner. Direct uptake studies confirmed that all three PBDE congeners are substrates for the three tested hepatic OATPs. Detailed kinetic analysis revealed that OATP1B1 transported 2,2',4,4'-tetrabromodiphenyl ether (BDE47) with the highest affinity (K(m) = 0.31 microM) followed by 2,2',4,4',5-pentabromodiphenyl ether (BDE99) (K(m) = 0.91 microM) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE153) (K(m) = 1.91 microM). For OATP1B3, the order was the same (BDE47: K(m) = 0.41 microM; BDE99: K(m) = 0.70 microM; BDE153: K(m) = 1.66 microM), while OATP2B1 transported all three congeners with similar affinities (BDE47: K(m) = 0.81 microM; BDE99: K(m) = 0.87 microM; BDE153: K(m) = 0.65 microM). These results clearly suggest that uptake of PBDEs via these OATPs is a mechanism responsible for liver-specific accumulation of PBDEs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.