羟基化多溴联苯醚(OH-PBDEs)在小鼠肝脏S9中的体外代谢研究

In vitro metabolism of Hydroxylation polybrominated diphenyl ethers in mice liver

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-OHBDE-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.

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.