Hydroxylation polybrominated diphenyl ethers (OH-PBDEs) are a class of phenolic compounds that have been found to be an endocrine disruptor, and the in vitro metabolism of OH-PBDEs and effect on metabolism of synthetic estrogen were investigated using mouse liver microsome. The results showed that all of the four OH-PBDEs can be metabolized, and the metabolic rate followed the order: 6-OH-BDE-99＞6'-OH-BDE-99＞6-OH-BDE-137＞5'-OH-BDE-99, which indicated OH-PBDEs were more readily bio-transformed when the hydroxyl functional group (-OH) was in the ortho position with the ether bond and the Br atom. The four OH-PBDEs showed different effects on the metabolism of natural estrogens, including estrone (E1), 17β-estradiol (E2), estriol (E3). As a whole, the inhibition on metabolic rate of E1 and E2 gradually increased with the increasing concentrations of OHPBDE, but showed a promotion effect on metabolism of E3 and no significant effect on metabolism of synthetic estrogen 17α-ethynylestradiol (EE2). The quantification of the metabolite 2-hydroxyestradiol (2-OH-E2) showed that6-OH-BDE-99 promoted the 2-OH-E2 production, while 2-OH-E2 production was inhibited by the other three OHPBDEs as the experimental concentration increased, and these results revealed that it may be related to the different metabolic mechanisms mediated by enzymes.%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,以小鼠肝脏微粒体作为研究对象,考察了OH-PBDEs的体外代谢行为及对雌激素代谢的影响.研究结果发现,4种OH-PBDE均能够代谢,其代谢率大小为6-OH-BDE-99＞6'-OH-BDE-99＞6-OH-BDE-137＞5'-OH-BDE-99,表明羟基官能团(-OH)与醚键及溴原子处于邻位时,表现出较高的代谢率;4种OH-PBDE对3种天然雌激素包括雌酮(E1)、17β-雌二醇(E2)、雌三醇(E3)的代谢表现出不同作用,整体来说,对E1和E2代谢随着OH-PBDE浓度的增加抑制作用逐渐增强,对E3代谢则表现出促进作用,但是对人工合成的雌激素17α-炔雌醇(EE2)无明显影响;对E2代谢产物2-羟基雌二醇(2-OH-E2)的生成量定量表征表明,除6-OH-BDE-99促进了2-OH-E2的生成量,其余3种OH-PBDE随实验添加浓度的增加,抑制了2-OH-E2的生成量,这可能与酶介导的不同代谢机制有关.
展开▼
