Human hydroxylated metabolites of BDE-47 and BDE-99 are glucuronidated and sulfated in vitro
| Autor: | Adrian Covaci, Göran Marsh, Claudio Erratico, Andreas Rydén, Xiaobo Zheng, Walid Maho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cytoplasm
Glucuronidation Ether 010501 environmental sciences Hydroxylation Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Glucuronides Sulfation Polybrominated diphenyl ethers Tandem Mass Spectrometry In vivo Halogenated Diphenyl Ethers Humans Organic chemistry 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Chromatography Molecular Structure Sulfates Chemistry Pharmacology. Therapy General Medicine Metabolism In vitro 3. Good health Kinetics 13. Climate action Microsomes Liver Microsome Biomarkers Chromatography Liquid |
| Zdroj: | Toxicology letters |
| ISSN: | 0378-4274 |
| Popis: | Polybrominated diphenyl ethers (PBDEs) were used worldwide as additive flame retardants and are classified as persistent, bioaccumulable and toxic environmental pollutants. In humans, the hydroxylated metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) formed in vitro have also been detected in vivo. To further characterize the metabolism of BDE-47 and BDE-99 and to identify candidate markers for monitoring the human exposure to PBDEs using non-invasive approaches, glucuronidation and sulfation of hydroxylated metabolites of BDE-47 and BDE-99 were investigated using human liver microsomes and cytoplasm, respectively. The formed Phase II metabolites were analyzed by liquid chromatography-tandem mass spectrometry using a novel approach to develop analytical methods in absence of authentic standards. All available standards for hydroxylated metabolites of BDE-47 and BDE-99 were glucuronidated and sulfated, showing that glucuronidation and sulfation are part of the metabolism pathway of BDE-47 and BDE-99 in vitro. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-47 were (a) 2,4-DBP-Gluc and 5-Gluc-BDE-47, and (b) 2'-Sulf-BDE-28, 4-Sulf-BDE-42 and 3-Sulf-BDE-47, respectively. The major glucuronidated and sulfated analogs of hydroxylated metabolites of BDE-99 were (a) 2,4,5-TBP-Gluc and 6'-Gluc-BDE-99, and (b) 3'-Sulf-BDE-99 and 5'-Sulf-BDE-99, respectively. Apparent K-m values associated with the formation of sulfated metabolites of BDE-47 and BDE-99 were ten times lower than those of the corresponding glucuronidated metabolites, suggesting that sulfated rather than glucuronidated metabolites of OH-PBDEs might be used as markers of human exposure to PBDEs using a non-invasive approach based on urine sample collection. (C) 2015 Elsevier Ireland Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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