In vitro metabolism of BDE-47, BDE-99, and α-, β-, γ-HBCD isomers by chicken liver microsomes

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In vitro metabolism of BDE-47, BDE-99, and α-, β-, γ-HBCD isomers by chicken liver microsomes. / Zheng, Xiaobo; Erratico, Claudio; Abdallah, Mohamed Abou Elwafa; Negreira, Noelia; Luo, Xiaojun; Mai, Bixian; Covaci, Adrian.

In: Environmental Research, Vol. 143, No. Part A, 11.2015, p. 221-228.

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Zheng, Xiaobo ; Erratico, Claudio ; Abdallah, Mohamed Abou Elwafa ; Negreira, Noelia ; Luo, Xiaojun ; Mai, Bixian ; Covaci, Adrian. / In vitro metabolism of BDE-47, BDE-99, and α-, β-, γ-HBCD isomers by chicken liver microsomes. In: Environmental Research. 2015 ; Vol. 143, No. Part A. pp. 221-228.

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@article{69c98df65ee345889b8d324480d10aae,
title = "In vitro metabolism of BDE-47, BDE-99, and α-, β-, γ-HBCD isomers by chicken liver microsomes",
abstract = "The in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and the individual α-, β- and γ-hexabromocyclododecane (HBCD) isomers catalyzed by cytochrome P450 (CYP) enzymes was studied using chicken liver microsomes (CLMs). Metabolites were identified using a liquid chromatography-tandem mass spectrometry method and authentic standards for the oxidative metabolites of BDE-47 and BDE-99. Six hydroxylated tetra-BDEs, namely 4-hydroxy-2,2',3,4'-tetrabromodiphenyl ether (4-OH-BDE-42), 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47), 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE-47), 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47), 4'-hydroxy-2,2',4,5'- tetrabromodiphenyl ether (4'-OH-BDE-49), and 2'-hydroxy-2,3',4,4'-tetrabromodiphenyl ether (2'-OH-BDE-66), were identified and quantified after incubation of BDE-47 with CLMs. 4'-OH-BDE-49 was the major metabolite formed. Three hydroxylated penta-BDEs (5'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE-99), 6'-hydroxy-2,2',4,4',5- pentabromodiphenyl ether (6'-OH-BDE-99), and 4'-hydroxy-2,2',4,5,5'-pentabromodiphenyl ether, 4'-OH-BDE-101, were formed incubating BDE-99 with CLMs. Concentrations of BDE-99 metabolites were lower than those of BDE-47. More than four mono-hydroxylated HBCD (OH-HBCD), more than four di-hydroxylated HBCD (di-OH-HBCD), more than five mono-hydroxylated pentabromocyclododecenes (OH-PBCD), and more than five di-hydroxylated pentabromocyclododecenes (di-OH-PBCD) were detected when α-, β-, or γ-HBCD were individually incubated with CLMs. Response values (the ratio between the peak areas of the target compound and its internal standard) for OH-HBCD were 1-3 orders of magnitude higher than those for OH-PBCD, di-OH-HBCD, and di-OH-PBCD, suggesting that OH-HBCD might be the major metabolites of α-, β- and γ-HBCD produced by CLMs. No diastereoisomeric or enantiomeric bioisomerisation was observed incubating α-, β- or γ-HBCD with CLMs. Collectively, our data suggest that (i) BDE-47 is metabolized at a faster rate than BDE-99 by CLMs, (ii) OH-HBCD are the major hydroxylated metabolites of α-, β- and γ-HBCD produced by CLMs and (iii) the diastereoisomeric or enantiomeric bioisomerisation of α-, β- and γ-HBCD is not mediated by chicken CYP enzymes.",
keywords = "Biotransformation, Chicken liver microsomes, Cytochrome P450, Hexabromocyclododecane, Polybrominated diphenyl ethers",
author = "Xiaobo Zheng and Claudio Erratico and Abdallah, {Mohamed Abou Elwafa} and Noelia Negreira and Xiaojun Luo and Bixian Mai and Adrian Covaci",
year = "2015",
month = nov,
doi = "10.1016/j.envres.2015.10.023",
language = "English",
volume = "143",
pages = "221--228",
journal = "Environmental Research",
issn = "0013-9351",
publisher = "Elsevier",
number = "Part A",

}

RIS

TY - JOUR

T1 - In vitro metabolism of BDE-47, BDE-99, and α-, β-, γ-HBCD isomers by chicken liver microsomes

AU - Zheng, Xiaobo

AU - Erratico, Claudio

AU - Abdallah, Mohamed Abou Elwafa

AU - Negreira, Noelia

AU - Luo, Xiaojun

AU - Mai, Bixian

AU - Covaci, Adrian

PY - 2015/11

Y1 - 2015/11

N2 - The in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and the individual α-, β- and γ-hexabromocyclododecane (HBCD) isomers catalyzed by cytochrome P450 (CYP) enzymes was studied using chicken liver microsomes (CLMs). Metabolites were identified using a liquid chromatography-tandem mass spectrometry method and authentic standards for the oxidative metabolites of BDE-47 and BDE-99. Six hydroxylated tetra-BDEs, namely 4-hydroxy-2,2',3,4'-tetrabromodiphenyl ether (4-OH-BDE-42), 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47), 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE-47), 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47), 4'-hydroxy-2,2',4,5'- tetrabromodiphenyl ether (4'-OH-BDE-49), and 2'-hydroxy-2,3',4,4'-tetrabromodiphenyl ether (2'-OH-BDE-66), were identified and quantified after incubation of BDE-47 with CLMs. 4'-OH-BDE-49 was the major metabolite formed. Three hydroxylated penta-BDEs (5'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE-99), 6'-hydroxy-2,2',4,4',5- pentabromodiphenyl ether (6'-OH-BDE-99), and 4'-hydroxy-2,2',4,5,5'-pentabromodiphenyl ether, 4'-OH-BDE-101, were formed incubating BDE-99 with CLMs. Concentrations of BDE-99 metabolites were lower than those of BDE-47. More than four mono-hydroxylated HBCD (OH-HBCD), more than four di-hydroxylated HBCD (di-OH-HBCD), more than five mono-hydroxylated pentabromocyclododecenes (OH-PBCD), and more than five di-hydroxylated pentabromocyclododecenes (di-OH-PBCD) were detected when α-, β-, or γ-HBCD were individually incubated with CLMs. Response values (the ratio between the peak areas of the target compound and its internal standard) for OH-HBCD were 1-3 orders of magnitude higher than those for OH-PBCD, di-OH-HBCD, and di-OH-PBCD, suggesting that OH-HBCD might be the major metabolites of α-, β- and γ-HBCD produced by CLMs. No diastereoisomeric or enantiomeric bioisomerisation was observed incubating α-, β- or γ-HBCD with CLMs. Collectively, our data suggest that (i) BDE-47 is metabolized at a faster rate than BDE-99 by CLMs, (ii) OH-HBCD are the major hydroxylated metabolites of α-, β- and γ-HBCD produced by CLMs and (iii) the diastereoisomeric or enantiomeric bioisomerisation of α-, β- and γ-HBCD is not mediated by chicken CYP enzymes.

AB - The in vitro oxidative metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and the individual α-, β- and γ-hexabromocyclododecane (HBCD) isomers catalyzed by cytochrome P450 (CYP) enzymes was studied using chicken liver microsomes (CLMs). Metabolites were identified using a liquid chromatography-tandem mass spectrometry method and authentic standards for the oxidative metabolites of BDE-47 and BDE-99. Six hydroxylated tetra-BDEs, namely 4-hydroxy-2,2',3,4'-tetrabromodiphenyl ether (4-OH-BDE-42), 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47), 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE-47), 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47), 4'-hydroxy-2,2',4,5'- tetrabromodiphenyl ether (4'-OH-BDE-49), and 2'-hydroxy-2,3',4,4'-tetrabromodiphenyl ether (2'-OH-BDE-66), were identified and quantified after incubation of BDE-47 with CLMs. 4'-OH-BDE-49 was the major metabolite formed. Three hydroxylated penta-BDEs (5'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (5'-OH-BDE-99), 6'-hydroxy-2,2',4,4',5- pentabromodiphenyl ether (6'-OH-BDE-99), and 4'-hydroxy-2,2',4,5,5'-pentabromodiphenyl ether, 4'-OH-BDE-101, were formed incubating BDE-99 with CLMs. Concentrations of BDE-99 metabolites were lower than those of BDE-47. More than four mono-hydroxylated HBCD (OH-HBCD), more than four di-hydroxylated HBCD (di-OH-HBCD), more than five mono-hydroxylated pentabromocyclododecenes (OH-PBCD), and more than five di-hydroxylated pentabromocyclododecenes (di-OH-PBCD) were detected when α-, β-, or γ-HBCD were individually incubated with CLMs. Response values (the ratio between the peak areas of the target compound and its internal standard) for OH-HBCD were 1-3 orders of magnitude higher than those for OH-PBCD, di-OH-HBCD, and di-OH-PBCD, suggesting that OH-HBCD might be the major metabolites of α-, β- and γ-HBCD produced by CLMs. No diastereoisomeric or enantiomeric bioisomerisation was observed incubating α-, β- or γ-HBCD with CLMs. Collectively, our data suggest that (i) BDE-47 is metabolized at a faster rate than BDE-99 by CLMs, (ii) OH-HBCD are the major hydroxylated metabolites of α-, β- and γ-HBCD produced by CLMs and (iii) the diastereoisomeric or enantiomeric bioisomerisation of α-, β- and γ-HBCD is not mediated by chicken CYP enzymes.

KW - Biotransformation

KW - Chicken liver microsomes

KW - Cytochrome P450

KW - Hexabromocyclododecane

KW - Polybrominated diphenyl ethers

UR - http://www.scopus.com/inward/record.url?scp=84945139286&partnerID=8YFLogxK

U2 - 10.1016/j.envres.2015.10.023

DO - 10.1016/j.envres.2015.10.023

M3 - Article

C2 - 26505652

AN - SCOPUS:84945139286

VL - 143

SP - 221

EP - 228

JO - Environmental Research

JF - Environmental Research

SN - 0013-9351

IS - Part A

ER -