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首页> 外文期刊>Environmental Science & Technology >Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes
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Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes

机译：鱼肝和肠微粒体中烷基有机磷酸酯的体外代谢动力学表征

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摘要

Tris(2-butoxyethyl) phosphate (TBOEP) and tris( n -butyl) phosphate (TNBP) are the most commonly used alkyl organophosphate esters (alkyl-OPEs), and they increasingly accumulate in organisms and create potential health hazards. This study examined the metabolism of TNBP and TBOEP in Carassius carassius liver and intestinal microsomes and the production of their corresponding monohydroxylated and dealkylated metabolites. After 140 min of incubation with fish liver microsomes, the rapid depletion of TNBP and TBOEP were both best fitted to the Michaelis–Menten model (at administrated concentrations ranging from 0.5 to 200 μM), with a CL _(int) (intrinsic clearance) of 3.1 and 3.9 μL·min~(–1)·mg~(–1) protein, respectively. But no significant ( P > 0.05) biotransformation was observed for these compounds in intestinal microsomes at any administrated concentrations. In fish liver microsomes assay, bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) and bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3-OH-TBOEP) were the most abundant metabolites of TBOEP, and dibutyl-3-hydroxybutyl phosphate (3-OH-TNBP) was the predominant metabolite of TNBP. Similarly, the apparent V _(max) values (maximum metabolic rate) of BBOEHEP and 3-OH-TNBP were also respectively highest among those of other metabolites. Further inhibition studies were conducted to identify the specific cytochrome P450 (CYP450) isozymes involved in the metabolism of TNBP and TBOEP in liver microsomes. It was confirmed that CYP3A4 and CYP1A were the significant CYP450 isoforms catalyzing the metabolism of TNBP and TBOEP in fish liver microsomes. Overall, this study emphasized the importance of hydroxylated metabolites as biomarkers for alkyl-OPEs exposure, and further research is needed to validate the in vivo formation and toxicological implications of these metabolites.
机译：磷酸三（2-丁氧基乙基）酯（TBOEP）和磷酸三（正丁酯）（TNBP）是最常用的烷基有机磷酸酯（烷基-OPE），它们越来越多地在生物体中积累并造成潜在的健康危害。这项研究检查了BP鱼肝脏和肠道微粒体中TNBP和TBOEP的代谢以及其相应的单羟基化和脱烷基化代谢产物的产生。与鱼肝微粒体温育140分钟后，TNBP和TBOEP的快速耗竭都最适合于Michaelis–Menten模型（给药浓度为0.5至200μM），CL _（int）（内在清除率）分别为3.1和3.9μL·min〜（–1）·mg〜（-1）蛋白。但是，在任何给药浓度下，这些化合物在肠道微粒体中均未观察到显着的（P> 0.05）生物转化。在鱼肝微粒体测定中，双（2-丁氧基乙基）羟乙基磷酸酯（BBOEHEP）和双（2-丁氧基乙基）3-羟基-2-丁氧基乙基磷酸酯（3-OH-TBOEP）是TBOEP中最丰富的代谢产物，而二丁基-磷酸3-羟丁酯（3-OH-TNBP）是TNBP的主要代谢产物。同样，BBOEHEP和3-OH-TNBP的表观V _（max）值（最大代谢率）在其他代谢物中也分别最高。进行了进一步的抑制研究，以鉴定参与肝微粒体TNBP和TBOEP代谢的特定细胞色素P450（CYP450）同工酶。证实CYP3A4和CYP1A是催化鱼肝微粒体中TNBP和TBOEP代谢的重要CYP450亚型。总的来说，这项研究强调了羟基化代谢物作为暴露于烷基-OPEs的生物标记物的重要性，还需要进一步的研究来验证这些代谢物的体内形成和毒理学意义。

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  • 来源
    《Environmental Science & Technology》 |2018年第5期|3202-3210|共9页
  • 作者

    Rui Hou; Chao Huang; Kaifeng Rao; Yiping Xu; Zijian Wang;

  • 作者单位

    Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China,University of Chinese Academy of Sciences, Beijing 100049, China;

    Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China,University of Chinese Academy of Sciences, Beijing 100049, China;

    State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;

    Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;

    State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;

  • 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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