Potent Competitive Interactions of Some Brominated Flame Retardants and Related Compounds with Human Transthyretin in Vitro

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Ranked #73 of 123 articles by views in toxicological sciences : an official journal of the society of toxicology

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Abstract
Brominated flame retardants such as polybrominated diphenyl ethers (PBDEs), pentabromophenol (PBP), and tetrabromobisphenol A (TBBPA) are produced in large quantities for use in electronic equipment, plastics, and building materials. Because these compounds have some structural resemblance to the thyroid hormone thyroxine (T4), it was suggested that they may interfere with thyroid hormone metabolism and transport, e.g., by competition with T4 on transthyretin (TTR). In the present study, we investigated the possible interaction of several brominated flame retardants with T4 binding to TTR in an in vitro competitive binding assay, using human TTR and 125 I-T4 as the displaceable radioligand. Compounds were tested in at least eight different concentrations ranging from 1.95 to 500 nM. In addition, we investigated the structural requirements of these and related ligands for competitive binding to TTR. We were able to show very potent competition binding for TBBPA and PBP (10.6- and 7.1-fold stronger than the natural ligand T4, respectively). PBDEs were able to compete with T4-TTR binding only after metabolic conversion by induced rat liver microsomes, suggesting an important role for hydroxylation. Brominated bisphenols with a high degree of bromination appeared to be more efficient competitors, whereas chlorinated bisphenols were less potent compared to their brominated analogues. These results indicate that brominated flame retardants, especially the brominated phenols and tetrabromobisphenol A, are very potent competitors for T4 binding to human transthyretin in vitro and may have effects on thyroid hormone homeostasis in vivo comparable to the thyroid-disrupting effects of PCBs.
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Authors Ilonka A.T.M. Meerts, Jelmer J. van Zanden, E. Luijks, Ingeborg van Leeuwen-Bol, E. Neil G. Marsh, Eva Jakobsson, Åke Bergman, Abraham Brouwer
Journal toxicological sciences : an official journal of the society of toxicology
Year 2000
DOI
10.1093/toxsci/56.1.95
URL
https://academic.oup.com/toxsci/article-pdf/56/1/95/10886548/056095.pdf
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