张易曦^1,2,
张圣虎^2,,,
吴永贵¹,
刘济宁²,
石利利²
1. 贵州大学 资源与环境工程学院, 贵阳 550025;
2. 环境保护部南京环境科学研究所, 南京 210042

作者简介: 张易曦(1989),女,硕士研究生,研究方向为环境毒理,E-mail:zhangyixi1021@icloud.com.

通讯作者: 张圣虎,zsh@nies.org ;

基金项目: 国家自然科学基金(21407055)
江苏省自然科学基金(BK20140115)


中图分类号: X171.5

In vitro Metabolism and Effects of Hydroxylation Polybrominated Diphenyl Ether (OH-PBDEs) within Mice Hepatic CYP450 Enzymes

Zhang Yixi^1,2,
Zhang Shenghu^2,,,
Wu Yonggui¹,
Liu Jining²,
Shi Lili²
1. College of Resources and Environmental Engineering, Guizhou University, Guiyang 550025, China;
2. Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection, Nanjing 210042, China

Corresponding author: Zhang Shenghu,zsh@nies.org ;

CLC number: X171.5

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摘要:羟基化多溴联苯醚(OH-PBDEs)是一类具有内分泌干扰效应的酚类化合物，生物毒性要高于母体多溴联苯醚(PBDEs)，研究OH-PBDEs的体外代谢行为对于理解其在生物体内的富集转化具有重要意义。以小鼠肝脏微粒体作为研究对象，考察了3-OH-BDE-47、5-OH-BDE-47、6-OH-BDE-47和2’-OH-BDE-68在小鼠肝脏中的体外代谢，并分别研究了浓度为0.1、0.2、0.4、0.6、1.0 μmol·L^-1条件下4种OH-PBDEs对细胞色素P450酶系中7-乙氧基香豆素-O-脱乙基酶(ECOD)、7-乙氧基异吩唑酮-O-脱乙基酶(EROD)和苯胺4-羟基化酶(ANH)活性的影响。结果表明，4种OH-PBDEs在小鼠肝脏微粒体中均能够快速代谢，代谢率分别为80%(3-OH-BDE-47)、42%(5-OH-BDE-47)、86%(6-OH-BDE-47)和63%(2’-OH-BDE-68)。实验所设OH-PBDEs各浓度对微粒体的ECOD活性无显著性抑制作用，但对EROD的活性均表现出相同的显著抑制作用；4种OH-PBDEs表现出不同的ANH活性影响，即3-OH-BDE-47对ANH活性具有抑制作用，5-OH-BDE-47具有诱导作用，而6-OH-BDE-47和2’-OH-BDE-68对ANH活性无显著性影响。
关键词: OH-PBDEs/
小鼠/
肝微粒体/
CYP450酶活/
体外代谢

Abstract:Hydroxylation polybrominateddiphenyl ethers (OH-PBDEs) are a class of phenolic compounds that have been found to be endocrine disruption, and their biological toxicity is higher than the polybrominateddiphenyl ethers (PBDEs). It is of great significance to investigate metabolic behavior of OH-PBDEs in vitro for a better understanding of their enrichment and transformation in vivo. The in vitro metabolism of 3-OH-BDE-47, 5-OH-BDE-47, 6-OH-BDE-47 and 2'-OH-BDE-68 was investigated using mouse liver microsome. In addation,the effects of four OH-PBDEs (0.1, 0.2, 0.4, 0.6 and 1 μmol·L^-1) on activities of 7-ethoxycoumarin O-deethylase (ECOD), 7-ethoxyresorufin O-deethylase (EROD) and aniline phydroxylase (ANH) were also evaluated. The results showed that four OH-PBDEs can be metabolized rapidly with the rate of 80% (3-OH-BDE-47)、42% (5-OH-BDE-47)、86% (6-OH-BDE-47) and 63% (2'-OH-BDE-68), respectively. Under these experimental conditions, four OH-PBDEs had no significant effect on ECOD activity, but all OH-PBDEs had inhibitory effect on EROD activity. In addition, four OH-PBDEs showed different effect on ANH activity. Specifically, 3-OH-BDE-47 had inhibitory effect on ANH activity, 5-OH-BDE-47 had induced effect on ANH activity, and 6-OH-BDE-47 and 2'-OH-BDE-68 had no significant effect, respectively.
Key words:OH-PBDEs/
mice/
liver microsome/
in vitro metabolism/
CYP450 enzyme activity.