Comparative Oxidative Metabolism of BDE-47 and BDE-99 by Rat Hepatic Microsomes
| العنوان: | Comparative Oxidative Metabolism of BDE-47 and BDE-99 by Rat Hepatic Microsomes |
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| المؤلفون: | Stelvio M. Bandiera, Claudio Erratico, Sarah Catherine Moffatt |
| المصدر: | Toxicological Sciences. 123:37-47 |
| بيانات النشر: | Oxford University Press (OUP), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Metabolite, Polybrominated Biphenyls, Ether, Toxicology, chemistry.chemical_compound, Polybrominated diphenyl ethers, Cytochrome P-450 Enzyme System, Halogenated Diphenyl Ethers, Animals, Rats, Long-Evans, Biotransformation, Flame Retardants, chemistry.chemical_classification, biology, Cytochrome P450, Metabolism, Rats, Metabolic pathway, Enzyme, chemistry, Biochemistry, Enzyme Induction, Microsomes, Liver, Microsome, biology.protein, Environmental Pollutants, Metabolic Detoxication, Phase I |
| الوصف: | Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that have become ubiquitous environmental pollutants. 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) are among the most prevalent PBDEs detected in humans, wildlife, and abiotic environmental matrices. The purpose of this study was to investigate the oxidative metabolism of BDE-47 and BDE-99 in rat hepatic microsomes by comparing metabolite formation rates, kinetic parameters associated with metabolite formation, and the effects of prototypical cytochrome P450 (CYP) inducers. The CYP enzymes involved were also identified. Incubation of BDE-47 with hepatic microsomes from phenobarbital-treated rats generated a total of five hydroxylated (OH-BDE) metabolites, among which 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether (4'-OH-BDE-49) and 3-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (3-OH-BDE-47) were the major metabolites, as identified using authentic standards and quantified by liquid chromatography/mass spectrometry. Incubations of BDE-99 with hepatic microsomes from dexamethasone-treated rats produced a total of seven hydroxylated metabolites, among which 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether (4-OH-BDE-90) and 6'-hydroxy-2,2',4,4',5-pentabromodiphenyl ether (6'-OH-BDE-99) were the major metabolites. Although the overall rate of oxidative metabolism of BDE-99 by hepatic microsomes was greater than that of BDE-47, para-hydroxylation involving a National Institutes of Health shift mechanism represented a major metabolic pathway for both PBDE congeners. Among the rat recombinant CYP enzymes tested, CYP2A2 and CYP3A1 were the most active in BDE-47 and BDE-99 metabolism, respectively. However, CYP1A1 exhibited the highest activity for 4'-OH-BDE-49 and 6'-OH-BDE-99 formation, and CYP3A1 exhibited the highest activity for 3-OH-BDE-47 and 4-OH-BDE-90 formation. Collectively, the results demonstrate that oxidative metabolism of BDE-47 and BDE-99 is mediated by distinct but overlapping sets of CYP enzymes and represents a key process that determines the bioaccumulation of BDE-47 and BDE-99 in mammals. |
| تدمد: | 1096-0929 1096-6080 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ae21c34e2e5da73a3ef1657cfdf03dc https://doi.org/10.1093/toxsci/kfr155 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9ae21c34e2e5da73a3ef1657cfdf03dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10960929 10966080 |
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