Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

In vitro metabolism of hydroxylated polybrominated diphenyl ethers and their inhibitory effects on 17β-estradiol metabolism in rat liver microsomes

Language

English

Abstract

Purpose: Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have emerged as contaminants of environmental concerns because they pose potential risks to human and animal health. The purpose of this study was to investigate the in vitro metabolism of OH-PBDEs and their potential inhibition against 17β-estradiol (E2) metabolism. Methods: Rat liver microsomes were used as a source of P450 enzymes in an in vitro metabolism study of OH-PBDEs. Inhibition of E2 metabolism and kinetic study were performed by incubating with rat liver microsomes in the presence of OH-PBDEs. Results: The obtained data clearly demonstrated that OH-PBDEs, especially those congeners with lower bromination, could be metabolized to bromophenol and diOH-PBDEs. The less metabolic rate of OH-PBDEs was observed with the increasing number of bromine substituents. OH-PBDEs with hydroxyl group and bromine adjacent to the ether bridge showed faster metabolic rates. In addition, the results showed non-competitive inhibition of E2 metabolism by OH-PBDEs with IC50 values in the range from 13. 7 to 55. 2 μM. The most potent OH-PBDE inhibitor was found to be 3′-OH-BDE-100. The inhibitory potencies for OH-PBDEs were significantly higher than those of parent PBDE and methoxylated metabolites, providing the evidence that PBDEs exerted estrogenic activity in part by their hydroxylated metabolites. Conclusions: OH-PBDEs exhibited large differences in their capacity to be metabolized and to inhibit E2 metabolism in rat liver microsomes. The finding might increase our understanding of healthy risk associated with PBDEs in human and wildlife. © 2012 Springer-Verlag.

Keywords

17β-Estradiol metabolism, diOH-PBDEs, Hydroxylated PBDEs, Inhibition, LC-MS, Metabolic rate

Publication Date

2012

Source Publication Title

Environmental Science and Pollution Research

Volume

19

Issue

8

Start Page

3219

End Page

3227

Publisher

Springer Verlag

DOI

10.1007/s11356-012-0828-x

Link to Publisher's Edition

http://dx.doi.org/10.1007/s11356-012-0828-x

ISSN (print)

09441344

ISSN (electronic)

16147499

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