title: Biotransformation of OH-PBDEs by pig liver microsomes: Investigating kinetics, identifying metabolites, and examining the role of different CYP isoforms.
abstract: Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of great concern due to their potential risk to animal and human health. The biotransformation potential of OH-PBDEs in organisms is important for the understanding of their health risk. In the present study, the biotransformation of 3'-OH-2,4-di-BDE (3'-OH-BDE-7), 4'-OH-2,2',4-tri-BDE (4'-OH-BDE-17) and 3-OH-2,2',4,4'-tetra-BDE (3-OH-BDE-47) by pig liver microsomes was studied. Compared with their precursor PBDEs, the three OH-PBDEs were more readily biotransformed by pig liver microsomes, and the biotransformation rate followed the order: 3'-OH-BDE-7 > 4'-OH-BDE-17 > 3-OH-BDE-47. These results revealed that the biotransformation rate of OH-PBDEs was decreased with an increase in the number of bromine substituents. Cleavage of the diphenyl ether bond was the dominant pathway for biotransformation of the three OH-PBDEs by pig liver microsomes, while debromination and hydroxylation were found to be of less importance. CYP3A4 was suggested to be the specific enzyme responsible for the biotransformation of OH-PBDEs via associated inhibition assay. These findings may enrich our understanding of health risk associated with OH-PBDEs in mammals and human beings.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection of the People's Republic of China, Nanjing 210042, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China.
authors.forename: Zhongkun
authors.initials: Z
authors.lastname: Du
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China. Electronic address: ecsxg@nju.edu.cn.
authors.forename: Shixiang
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D055768:Halogenated Diphenyl Ethers / Q000032:analysis* / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D057230:Limit of Detection; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D013552:Swine
chemical_list: D055768:Halogenated Diphenyl Ethers; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System
keywords: Biotransformation; Enzyme; Hydroxylated polybrominated diphenyl ethers; Pig liver microsomes