Metabolite alterations in zebrafish embryos exposed to hydroxylated polybrominated diphenyl ethers

Johan Gustafsson*, Jessica Legradi, Marja H. Lamoree, Lillemor Asplund, Pim E.G. Leonards

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are formed by metabolism from the flame retardants polybrominated diphenyl ethers (PBDEs). In the aquatic environment, they are also produced naturally. OH-PBDEs are known for their potential to disrupt energy metabolism, the endocrine system, and the nervous system. This is the first study focusing on the effects of OH-PBDEs at the metabolite level in vivo. The aim of the current study was to investigate the metabolic effects of exposure to OH-PBDEs using metabolomics, and to identify potential biomarker(s) for energy disruption of OH-PBDEs. Zebrafish (Danio rerio) embryos were exposed to two different concentrations of 6-OH-BDE47 and 6-OH-BDE85 and a mixture of these two compounds. In total, 342 metabolites were annotated and 79 metabolites were affected in at least one exposure. Several affected metabolites, e.g. succinic acid, glutamic acid, glutamine, tyrosine, tryptophan, adenine, and several fatty acids, could be connected to known toxic mechanisms of OH-PBDEs. Several phospholipids were strongly up-regulated with up to a six-fold increase after exposure to 6-OH-BDE47, a scarcely described effect of OH-PBDEs. Based on the observed metabolic effects, a possible connection between disruption of the energy metabolism, neurotoxicity and potential immunotoxicity of OH-PBDEs was suggested. Single compound exposures to 6-OH-BDE47 and 6-OH-BDE85 showed little overlap in the affected metabolites. This shows that compounds of similar chemical structure can induce different metabolic effects, possibly relating to their different toxic mechanisms. There were inter-concentration differences in the metabolic profiles, indicating that the metabolic effects were concentration dependent. After exposure to the mixture of 6-OH-BDE47 and 6-OH-BDE85, a new metabolic profile distinct from the profiles obtained from the single compounds was observed. Succinic acid was up-regulated at the highest, but still environmentally relevant, concentration of 6-OH-BDE47, 6-OH-BDE85, and the mixture. Therefore, succinic acid is suggested as a potential biomarker for energy disruption of OH-PBDEs.

Original languageEnglish
Article number159269
JournalScience of the Total Environment
Volume857
DOIs
Publication statusPublished - 20 Jan 2023

Bibliographical note

Funding Information:
The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas) (Contract Dnr: 942-2015-944 ) is acknowledged for financing the project. Jacco Koekkoek, Martin van Velzen, Peter Cenijn, and Marijke Wagner are acknowledged for assistance with chemical analysis.

Publisher Copyright:
© 2022 The Authors

Funding

The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas) (Contract Dnr: 942-2015-944 ) is acknowledged for financing the project. Jacco Koekkoek, Martin van Velzen, Peter Cenijn, and Marijke Wagner are acknowledged for assistance with chemical analysis.

Keywords

  • 6-OH-BDE47
  • Flame retardant
  • Metabolomics
  • Mixture
  • OH-PBDE
  • Zebrafish

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