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首页> 外文期刊>Environmental Science & Technology >Hepatic Metabolism Affects the Atropselective Disposition of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) in Mice
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Hepatic Metabolism Affects the Atropselective Disposition of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) in Mice

机译：肝代谢影响小鼠中2,2'，3,3'，6,6'-六氯联苯（PCB 136）的Atropselective配置

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摘要

To understand the role of hepatic vs extrahepatic metabolism in the disposition of chiral PCBs, we studied the disposition of 2,2′,3,3′,6,6′-hexachlorobiphenyl (PCB 136) and its hydroxylated metabolites (HO-PCBs) in mice with defective hepatic metabolism due to the liver-specific deletion of cytochrome P450 oxidoreductase (KO mice). Female KO and congenic wild type (WT) mice were treated with racemic PCB 136, and levels and chiral signatures of PCB 136 and HO-PCBs were determined in tissues and excreta 3 days after PCB administration. PCB 136 tissue levels were higher in KO compared to WT mice. Feces was a major route of PCB metabolite excretion, with 2,2′,3,3′,6,6′-hexachlorobiphenyl-5-ol being the major metabolite recovered from feces. (+)-PCB 136, the second eluting PCB 136 atropisomers, was enriched in all tissues and excreta. The second eluting atropisomers of the HO-PCBs metabolites were enriched in blood and liver; 2,2′,3,3′,6,6′-hexachlorobiphenyl-5-ol in blood was an exception and displayed an enrichment of the first eluting atropisomers. Fecal HO-PCB levels and chiral signatures changed with time and differed between KO and WT mice, with larger HO-PCB enantiomeric fractions in WT compared to KO mice. Our results demonstrate that hepatic and, possibly, extrahepatic cytochrome P450 (P450) enzymes play a role in the disposition of PCBs.
机译：为了了解肝代谢与肝外代谢在手性多氯联苯处理中的作用，我们研究了2,2'，3,3'，6,6'-六氯联苯（PCB 136）及其羟基化代谢产物（HO-PCBs）的处理在肝脏代谢缺陷的小鼠中，由于细胞色素P450氧化还原酶的肝特异性缺失而引起的小鼠（KO小鼠）。用消旋PCB 136处理雌性KO和同基因野生型（WT）小鼠，并在施用PCB后3天确定组织和排泄物中PCB 136和HO-PCB的水平和手性特征。与野生型小鼠相比，KO中的PCB 136组织水平更高。粪便是PCB代谢产物排泄的主要途径，其中2,2'，3,3'，6,6'-六氯联苯-5-醇是从粪便中回收的主要代谢产物。 （+）-PCB 136，第二种洗脱的PCB 136阻转异构体，在所有组织和排泄物中富集。 HO-PCBs代谢物的第二次洗脱的阻转异构体富含血液和肝脏；血液中的2,2'，3,3'，6,6'-六氯联苯-5-醇是一个例外，显示了最初洗脱的阻转异构体的富集。粪中HO-PCB的水平和手性签名随时间变化，并且在KO和WT小鼠之间有所不同，与KO小鼠相比，WT中的HO-PCB对映体分数更大。我们的结果表明，肝以及可能的肝外细胞色素P450（P450）酶在PCB的处理中发挥了作用。

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  • 来源
    《Environmental Science & Technology》 |2015年第1期|616-625|共10页
  • 作者

    Xianai Wu; Christopher Barnhart; Pamela J. Lein; Hans-Joachim Lehmler;

  • 作者单位

    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa 52242, United States;

    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States;

    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States;

    Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa 52242, United States,Department of Occupational and Environmental Health, The University of Iowa, University of Iowa Research Park, #221 IREH, Iowa City, IA 52242-5000;

  • 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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