title: Disruption of oxidative phosphorylation (OXPHOS) by hydroxylated polybrominated diphenyl ethers (OH-PBDEs) present in the marine environment.
abstract: Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of growing concern, as they have been detected in both humans and wildlife and have been shown to be toxic. Recent studies have indicated that OH-PBDEs can be more toxic than PBDEs, partly due to their ability to disrupt oxidative phosphorylation (OXPHOS), an essential process in energy metabolism. In this study, we determined the OXPHOS disruption potential of 18 OH-PBDE congeners reported in marine wildlife using two in vitro bioassays, namely the classic rat mitochondrial respiration assay, and a mitochondrial membrane potential assay using zebrafish PAC2 cells. Single OH-PBDE congeners as well as mixtures were tested to study potential additive or synergistic effects. An environmental mixture composed of seven OH-PBDE congeners mimicking the concentrations reported in Baltic blue mussels were also studied. We report that all OH-PBDEs tested were able to disrupt OXPHOS via either protonophoric uncoupling and/or inhibition of the electron transport chain. Additionally we show that OH-PBDEs tested in combinations as found in the environment have the potential to disrupt OXPHOS. Importantly, mixtures of OH-PBDEs may show very strong synergistic effects, stressing the importance of further research on the in vivo impacts of these compounds in the environment.
authors.affiliation: Institute for Environmental Studies, VU University Amsterdam , De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Legradi
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Dahlberg
authors.forename: Peter
authors.initials: P
authors.lastname: Cenijn
authors.forename: Göran
authors.initials: G
authors.lastname: Marsh
authors.forename: Lillemor
authors.initials: L
authors.lastname: Asplund
authors.forename: Åke
authors.initials: Å
authors.lastname: Bergman
authors.forename: Juliette
authors.initials: J
authors.lastname: Legler
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054750:Ecotoxicology / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D006900:Hydroxylation; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D049880:Mytilus edulis / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology
chemical_list: D055768:Halogenated Diphenyl Ethers; D014874:Water Pollutants, Chemical; D000255:Adenosine Triphosphate