典型羟基化多溴联苯醚(OH-PBDEs)小鼠肝微粒体的体外代谢及关键代谢CYP450酶系的研究

Research on in vitro metabolism of typical hydroxylated polybrominated diphenyl ethers (OH-PBDEs) in mouse liver microsomes and the key CYP450 enzyme system

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,本研究以小鼠肝脏微粒体作为研究对象,考察了4种典型OH-PBDEs(3-OH-BDE-47、5-OH-BDE-47、6-OH-BDE-47和2′-OH-BDE-68)的体外代谢.研究结果表明,4种OH-PBDEs在小鼠肝脏微粒体中均能被代谢;OH-PBDE结构上的醚键(O)、羟基(OH)和溴原子(Br)的相对位置会影响其代谢效率,OH位于苯环上醚键邻位更有利于其代谢,即6-OH-BDE-47表现出相对较高的代谢率;抑制剂实验发现CYP1A2和CYP3A4是4种典型OH-PBDEs主要的CYP450代谢亚型.

Hydroxylation polybrominateddiphenyl ethers(OH PBDEs)are a class of phenolic compounds that have been found to be endocrine disruption,the in vitro metabolism of four typical kinds of OH PBDEs(3 OH BDE 47、5 OH BDE 47、6 OH BDE 47 and 2′ OH BDE 68)were investigated using mouse liver microsome in this study.The results show that the four kinds of OH PBDEs could be metabolized in the mouse liver microsome;the relative positions of ether bond(O),hydroxyl(OH)and bromine atom(Br)in OH PBDE structure would affect its metabolic efficiency,and OH PBDEs with hydroxyl group adjacent to the ortho position of the ether bond on the benzene ring showed faster metabolic rates,i.e.6 OH BDE 47 had a relatively high metabolic rate;Inhibitor experiments found that CYP1A2 and CYP3A4 were the major CYP450 metabolic subtypes of four typical OH PBDEs.