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,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。
Abstract:
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 OHPBDEs can be metabolized, and the metabolic rate followed the order:6-OH-BDE-99 > 6'-OH-BDE-99 > 6-OHBDE-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 OH-PBDE, 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 that 6-OH-BDE-99 promoted the 2-OH-E2 production, while 2-OH-E2 production was inhibited by the other three OH-PBDEs as the experimental concentration increased, and these results revealed that it may be related to the different metabolic mechanisms mediated by enzymes.