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[PMID]: | 29306024 |
[Au] Autor: | Hill KL; Hamers T; Kamstra JH; Willmore WG; Letcher RJ |
[Ad] Endereço: | Ecotoxicology and Wildlife Health Division, Environment and Climate Change Canada, National Wildlife Research Centre, Carleton University, Ottawa, Canada; Department of Biology, Carleton University, Ottawa, Canada; Intrinsik Corp., Ottawa, Canada. |
[Ti] Título: | Organophosphate triesters and selected metabolites enhance binding of thyroxine to human transthyretin in vitro. |
[So] Source: | Toxicol Lett;285:87-93, 2018 Mar 15. | [Is] ISSN: | 1879-3169 |
[Cp] País de publicação: | Netherlands |
[La] Idioma: | eng |
[Ab] Resumo: | The toxicological properties of organophosphate (OP) triesters that are used as flame retardants and plasticizers are currently not well understood, though increasing evidence suggests they can affect the thyroid system. Perturbation of thyroid hormone (TH) transport is one mechanism of action that may affect thyroid function. The present study applied an in vitro competitive protein binding assay with thyroxine (T4) and human transthyretin (hTTR) transport protein to determine the potential for the OP triesters, TDCIPP (tris(1,3-dichloro-2-propyl) phosphate), TBOEP (tris(butoxyethyl) phosphate), TEP (triethyl phosphate), TPHP (triphenyl phosphate), p-OH-TPHP (para-hydroxy triphenyl phosphate), and the OP diester DPHP (diphenyl phosphate), to competitively displace T4 from hTTR. Enhancement of T4 binding to hTTR, rather than the hypothesized competition, was observed for the six OP esters and in a concentration-dependent manner. For example, T4-hTTR binding was significantly increased at concentrations of TBOEP as low as 64 nM, and up to 184% of controls at 5000 nM. A plausible explanation of these results, which to our knowledge has not been previously reported, may be allosteric interactions of the OP esters with hTTR allowing T4 to access the second site of the TH binding pocket. These in vitro results suggest a novel mechanism of OP ester toxicity via T4 binding enhancement, and possible dysregulation of T4-hTTR interactions. |
[Mh] Termos MeSH primário: |
Retardadores de Chama/toxicidade Organofosfatos/toxicidade Plastificantes/toxicidade Pré-Albumina/metabolismo Tiroxina/metabolismo
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[Mh] Termos MeSH secundário: |
Ligação Competitiva Ésteres Retardadores de Chama/metabolismo Seres Humanos Organofosfatos/metabolismo Plastificantes/metabolismo Ligação Proteica Glândula Tireoide/efeitos dos fármacos Glândula Tireoide/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Esters); 0 (Flame Retardants); 0 (Organophosphates); 0 (Plasticizers); 0 (Prealbumin); Q51BO43MG4 (Thyroxine) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180219 |
[Lr] Data última revisão:
| 180219 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180107 |
[St] Status: | MEDLINE |
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