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张易曦,张芹,吉贵祥,徐怀洲,张圣虎,刘济宁,石利利.羟基化多溴联苯醚(OH-PBDEs)在小鼠肝脏S9中的体外代谢研究[J].环境科学学报,2016,36(9):3480-3487

In vitro metabolism of Hydroxylation polybrominated diphenyl ethers in mice liver

基金项目：国家自然科学基金（No.21407055）；江苏省自然科学基金（No.BK20140115）；中央级公益性科研院所基本科研业务专项（2015）

摘要：羟基化多溴联苯醚（OH-PBDEs）是一类具有内分泌干扰性质的酚类化合物，且内分泌干扰效应大于其母体多溴联苯醚（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S9部分作为研究对象，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.结果表明小鼠肝脏S9中的I相酶和II相酶均能代谢4种OH-PBDEs；醚键与OH官能团及Br原子互为邻位时，I相酶对OH-PBDEs的代谢率最高，即6-OH-BDE-47表现出较高的代谢率，此外，4种OH-PBDEs经I相酶代谢后均能生成2，4-二溴苯酚，表明醚键断裂是其主要的I相酶代谢途径；OH-PBDEs的OH官能团与醚键互为间位时，II相酶对其葡萄糖醛酸结合反应最高，也就是5-OH-BDE-47表现出较高的去除率.

Abstract：Hydroxylation polybrominateddiphenyl ethers (OH-PBDEs) are a class of phenolic compounds that have endocrine disruption effects, and their biological toxicity is higher than 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 S9 fraction. The results showed that four OH-PBDEs can be metabolized by I phase and II phase enzyme. OH-PBDEs with hydroxyl group and bromine adjacent to the etherbond showed faster metabolic rates, i.e. 6-OH-BDE-47 had much faster metabolic rates. In addition, 2, 4-dibromophenol was detected in the metabolic product of all of the 4 OH-PBDEs by I phase enzyme, suggesting that cleavage of the diphenyl ether bond was the dominant pathway. II phase enzyme was more likely to react with OH-PBDEs with hydroxyl group at meta position than the ether bond, i.e. 5-OH-BDE-47 showed a high removal rate.

Key words：hydroxylated polybrominated diphenyl ethers(OH-PBDEs) liver S9 in vitro metabolism CYP450 UGT