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首页> 外文期刊>Environmental Science & Technology >Impacts of Unregulated Novel Brominated Flame Retardants on Human Liver Thyroid Deiodination and Sulfotransferation
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Impacts of Unregulated Novel Brominated Flame Retardants on Human Liver Thyroid Deiodination and Sulfotransferation

机译:不受管制的新型溴化阻燃剂对人甲状腺甲状腺脱碘和硫转移的影响

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摘要

The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-rribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethyIhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP), and β-tetrabromoethylcyclohexane (β-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations. Only DBDPE showed inhibition of both outer and inner ring deiodination (O and IRD) of T3 and 3,3'-T2 formation from T4, respectively, with an estimated IC_(50) of 160 nM; no statistically significant inhibition of SULT activity was observed. ORD inhibition of 3,3'-T2 formation from rT3 was also observed (IC_(50) ~ 100 nM). The kinetics of T4 O and IRD were also investigated, although a definitive mechanism could not be identified as the Michaelis-Menten parameters and maximal rate constants were not significantly different. Concentrations tested were intentionally above expected environmental levels, and this study suggests that these NBFRs are not potent human liver DIO and SULT inhibitors. To our knowledge, DBDPE is the first example of a nonhydroxylated contaminant inhibiting DIO activity, and further study of the mechanism of action is warranted.
机译:五种新型溴化阻燃剂1,2,2-双(2,4,5-三溴苯氧基)乙烷(BTBPE),十溴二苯乙烷(DBDPE),2-乙基己基-2,3,4,5-四溴苯甲酸酯(EH- (TBB),双(2-乙基己基)-四溴邻苯二甲酸酯(BEH-TEBP)和β-四溴乙基环己烷(β-TBECH)对甲状腺激素脱碘酶(DIO)和磺基转移酶(SULT)的活性使用人体外肝微粒体和胞质进行了研究生物测定。通过将活性人肝亚细胞级分与甲状腺激素(分别为T4和rT3)孵育,并测量甲状腺激素(T4,T3,rT3和3,3'-T2)浓度的变化来测量酶活性。仅DBDPE显示出对T3的T3和3,3'-T2形成的外环和内环去碘化(O和IRD)的抑制,估计IC_(50)为160 nM;没有观察到SULT活性的统计学显着抑制。还观察到ORD抑制了rT3中3,3'-T2的形成(IC_(50)〜100 nM)。还研究了T4 O和IRD的动力学,尽管无法确定确定的机理,因为Michaelis-Menten参数和最大速率常数没有显着差异。测试的浓度有意高于预期的环境水平,这项研究表明这些NBFR不是有效的人肝DIO和SULT抑制剂。据我们所知,DBDPE是抑制DIO活性的非羟基化污染物的第一个实例,因此有必要进一步研究其作用机理。

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  • 来源
    《Environmental Science & Technology》 |2017年第12期|7245-7253|共9页
  • 作者单位

    Department of Chemistry, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;

    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States;

    Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States;

    Department of Fisheries and Oceans Canada, Freshwater Institute, Winnipeg, MB R3T 2N6, Canada;

    Fort Richmond Collegiate, Winnipeg, MB R3T 3B3, Canada;

    Department of Chemistry, McGill University, Montreal, QC H3A 0G4, Canada;

    Wellington Laboratories, Inc., 345 Southgate Drive, Guelph, ON N1G 3M5, Canada;

    Wellington Laboratories, Inc., 345 Southgate Drive, Guelph, ON N1G 3M5, Canada;

    Department of Chemistry, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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