陈玫宏;徐怀洲;宋宁慧;张芹;张圣虎;李江;

• 1:生态环境部南京环境科学研究所
• 2:贵州大学资源与环境工程学院

摘要(Abstract)：

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。

关键词(KeyWords)： OH-PBDEs;肝脏微粒体;体外代谢;雌激素

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(No.21407055,51508120)

作者(Author): 陈玫宏;徐怀洲;宋宁慧;张芹;张圣虎;李江;

Email:

参考文献(References)：

• [1] Usenko C Y,Hopkins D C,Trumble S J,et al. Hydroxylated PBDEs induce developmental arrest in zebrafish[J]. Toxicology&Applied Pharmacology,2012,262(1):43-51
• [2] Macaulay L J,Chen A,Rock K D,et al. Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptorβ[J].Aquatic Toxicology,2015,168(3):38-47
• [3] Li T,Wang W,Pan Y W,et al. A hydroxylated metabolite of flame-retardant PBDE-47 decreases the survival,proliferation,and neuronal differentiation of primary cultured adult neural stem cells and interferes with signaling of ERK5 MAP kinase and neurotrophin 3[J]. Toxicological Sciences,2013,134(1):111-124
• [4]施玉泉,闻胜,李敬光,等.固相萃取-超高效液相色谱-电喷雾离子源-串联质谱法测定人血中羟基化多溴联苯醚[J].中国食品卫生杂志,2012,4(24):317-321Shi Y Q,Wen S,Li J G,et al. Determination of hydroxylated polybrominated diphenyl ethers in human blood by solid phase extraction-ultra-performance liquid chromatography-electrospray ionization-ion tandem mass spectrometry[J]. Chinese Journal of Food Hygiene,2012,4(24):317-321(in Chinese)
• [5] Legradi J,Pomeren M V,Dahlberg A K,et al. Effects ofhydroxylated polybrominated diphenyl ethers in developing zebrafish are indicative of disruption of oxidative phosphorylation[J]. International Journal of Molecular Sciences,2017,18(5):970
• [6] Liu D,Wu S M,Zhang Q,et al. Occurrence,spatial distribution,and ecological risks of typical hydroxylated polybrominated diphenyl ethers in surface sediments from a large freshwater lake of China[J]. Environmental Science&Pollution Research,2017,24(6):1-8
• [7] Fan Y,Lan J,Li H,et al. Spatial distributions of methoxylated and hydroxylated polybrominated diphenyl ethers in the East China Sea—A seaward increasing trend[J]. Chemosphere,2014,114(1):247-254
• [8] Zhang K,Wan Y,Jones P D,et al. Occurrences and fates of hydroxylated polybrominated diphenyl ethers in marine sediments in relation to trophodynamics[J]. Environmental Science&Technology,2012,46(4):2148-2155
• [9] Malmberg T,Athanasiadou M,Marsh G,et al. Identification of hydroxylated polybrominated diphenyl ether metabolites in blood plasma from polybrominated diphenyl ether exposed rats[J]. Environmental Science&Technology,2005,39(14):5342-5348
• [10] Mizukawa H,Nomiyama K,Nakatsu S,et al. Organohalogen compounds in pet dog and cat:Do pets biotransform natural brominated products in food to harmful hydroxlated substances?[J]. Environmental Science&Technology,2016,50(1):444-452
• [11] Zhu L,Ma B,Hites R A. Brominated flame retardants in serum from the general population in northern China[J]. Environmental Science&Technology,2009,43(18):6963-6968
• [12] Morellofrosch R,Cushing L J,Jesdale B M,et al. Environmental chemicals in an urban population of pregnant women and their newborns from San Francisco[J].European Neurology,2016,43(2):102-106
• [13] Wang Y,Liu S,Zhao H,et al. Polybrominated diphenylethers(PBDEs)and their hydroxylated metabolites(OH-PBDEs)in female serum from Dalian,China[J].International Journal of Hygiene&Environmental Health,2016,219(8):816-822
• [14] Wang H S,Chen Z J,Ho K L,et al. Hydroxylated and methoxylated polybrominated diphenyl ethers in blood plasma of humans in Hong Kong[J]. Environment International,2012,47(16):66-72
• [15]张易曦,张芹,吉贵祥,等.羟基化多溴联苯醚(OHPBDEs)在小鼠肝脏S9中的体外代谢研究[J].环境科学学报,2016,36(9):3480-3487Zhang Y X,Zhang Q,Ji G X,et al. Metabolism of hydroxylated polybrominated diphenyl ethers(OH-PBDEs)in mouse liver S9 in vitro[J]. Acta Scientiae Circumstantiae,2016,36(9):3480-3487(in Chinese)
• [16] Li J,Zhang Y,Du Z,et al. Biotransformation of OHPBDEs by pig liver microsomes:Investigating kinetics,identifying metabolites,and examining the role of different CYP isoforms[J]. Chemosphere,2016,148:354-360
• [17]赖永权,陈学国,蔡宗苇.羟基多溴联苯醚(3’-OHBDE-7)的大鼠体外肝代谢研究[J].环境化学,2011,30(1):346-350Lai Y Q,Chen X G,Cai Z W. Liver metabolism of hydroxy polybrominated diphenyl ethers(3'-OH-BDE-7)in rats[J]. Environmental Chemistry,2011,30(1):346-350(in Chinese)
• [18]张易曦,张圣虎,吴永贵,等.羟基化多溴联苯醚(OH-PBDEs)在小鼠肝脏微粒体的体外代谢及对CYP450酶活性的影响[J].生态毒理学报,2016,11(2):693-701Zhang Y X,Zhang S H,Wu Y G,et al. Metabolism of hydroxylated polybrominated diphenyl ethers(OH-PBDEs)in mouse liver microsomes in vitro and its effect on CYP450 enzyme activity[J]. Asian Journal of Ecotoxicology,2016,11(2):693-701(in Chinese)
• [19] Qiu X,Bigsby R M,Hites R A. Hydroxylated metabolites of polybrominated diphenyl ethers in human blood samples from the United States[J]. Environmental Health Perspectives,2009,117(1):93-98
• [20] Christopher L. The effects of brominated flame retardants on thyroid hormone homeostasis in human placenta tissues and cell culture[D]. Durham,North Carolina:Duke University,2016
• [21] Simon C R. PBDE metabolism and effects on thyroid hormone regulation in human astrocytes[D]. Durham,North Carolina:Duke University,2014
• [22] Kretschmer X C,Baldwin W S. CAR and PXR:Xenosensors of endocrine disrupters?[J]. Chemico-Biological Interactions,2005,155(3):111-128
• [23] Hamers T,Kamstra J H,Sonneveld E,et al. Biotransformation of brominated flame retardants into potentially endocrine-disrupting metabolites,with special attention to 2,2',4,4'-tetrabromodiphenyl ether(BDE-47)[J].Molecular Nutrition&Food Research,2008,52(2):284-298
• [24] Kester M H A,Bulduk S,van Toor H,et al. Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites of polyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters[J]. Clinical Endocrinology&Metabolism,2002,87(3):1142-1150
• [25]程泽能,周宏灏.雌激素的代谢机制及其与疾病的相关性[J].中国临床药理学杂志,2000,16(4):304-308Cheng Z N,Zhou H H. Metabolic mechanism of estrogen and its correlation with disease[J]. Chinese Journal of Clinical Pharmacology,2000,16(4):304-308(in Chinese)
• [26] Lai Y Q,Cai Z W. In vitro metabolism of hydroxylated polybrominated diphenyl ethers and their inhibitory effects on 17β-estradiol metabolism in rat liver microsomes[J]. Environmental Science&Pollution Research,2012,19(8):3219-3227
• [27]谢晴.多溴联苯醚及其羟基化衍生物的环境光化学转化[D].大连:大连理工大学,2011Xie Q. Environmental photochemical conversion of polybrominated diphenyl ethers and their hydroxylated derivatives[D]. Dalian:Dalian University of Technology,2011
• [28] Shimada K,Masue T,Chiba H. Application of inclusion chromatography to the determination of in vitro metabolites of estriol[J]. Journal of Chromatographic Science,1989,27:557-560
• [29] Shou M,Korzekwa K R,Brooks E N,et al. Role of human hepatic cytochrome P450 1A2 and 3A4 in the metabolic activation of estrone[J]. Carsinogenesis,1997,18:207-214
• [30] Usmani K A,Cho T M,Rose R L,et al. Inhibition of the human liver microsomal and human cytochrome P4501A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals[J]. Drug Metabolism&Disposition,2006,34(9):1606-1614