title: Toxicity of brominated flame retardants, BDE-47 and BDE-99 stems from impaired mitochondrial bioenergetics.
abstract: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants, and they have been detected in human blood, adipose tissue and breast milk, a consequence of their physicochemical and bioaccumulative properties, as well as their high environmental persistence. Many studies report liver toxicity related to exposure to PBDEs. In the present study, we investigated the toxicity of BDE-47 and BDE-99 at concentrations ranging from 0.1 to 50 µM in isolated rat liver mitochondria. We evaluated how incubation of a mitochondrial suspension with the PBDEs affected the mitochondrial inner membrane, membrane potential, oxygen consumption, calcium release, mitochondrial swelling, and ATP levels to find out whether the tested compound interfered with the bioenergetics of this organelle. Both PBDEs were toxic to mitochondria: BDE-47 and BDE-99 concentrations equal to or higher than 25 and 50 µM, respectively, modified all the parameters used to assess mitochondrial bioenergetics, which culminated in ATP depletion. These effects stemmed from the ability of both PBDEs to cause Membrane Permeability Transition (MPT) in mitochondria, which impaired mitochondrial bioenergetics. In particular, BDE-47, which has fewer bromine atoms in the molecule, can easily overcome biological membranes what would be responsible for the major negative effects exerted by this congener when compared with BDE-99.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo , Ribeirão Preto, São Paulo , Brazil and.
authors.forename: Murilo
authors.initials: M
authors.lastname: Pazin
authors.forename: Lilian Cristina
authors.initials: LC
authors.lastname: Pereira
authors.forename: Daniel Junqueira
authors.initials: DJ
authors.lastname: Dorta
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D000255:Adenosine Triphosphate; C572625:2,2',4,5'-tetrabromodiphenyl ether; D002118:Calcium
keywords: ATP depletion; PBDEs; bioenergetics; mitochondria