title: BDE-154 induces mitochondrial permeability transition and impairs mitochondrial bioenergetics.
abstract: Brominated flame retardants are used in various consumer goods to make these materials difficult to burn. Polybrominated diphenyl ethers (PBDE), which are representative of this class of retardants, consist of two benzene rings linked by an oxygen atom, and contain between 1 and 10 bromine atoms in their chemical structure, with the possibility of up to 209 different congeners. Among these congeners, BDE-154 (hexa-BDE) is persistent in the environment and easy to detect in the biota, but no apparent information regarding the mechanism underlying action and toxicity is available. Mitochondria, as the main energy-producing organelles, play an important role in the maintenance of various cellular functions. Therefore, mitochondria were used in the present study as an experimental model to determine the effects of BDE-154 congener at concentrations ranging from 0.1 μM to 50 μM. Our results demonstrated that BDE-154 interacts with the mitochondrial membrane, preferably by inserting into the hydrophobic core of the mitochondrial membrane, which partially inhibits respiration, dissipates Δψ, and permeabilizes the inner mitochondrial membrane to deplete ATP. These effects are more pronounced at concentrations equal to or higher than 10 μM. Results also showed that BDE-154 did not induce reactive oxygen species (ROS) accumulation within the mitochondria, indicating the absence of oxidative stress. Therefore, BDE-154 impairs mitochondrial bioenergetics and permeabilizes the mitochondrial membrane, potentially leading to cell death but not via mechanisms involving oxidative stress.
authors.affiliation: a Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Departamento de Análises Clínicas , Toxicológicas e Bromatológicas, Universidade de São Paulo , Ribeirão Preto , São Paulo , Brasil.
authors.forename: Lílian Cristina
authors.initials: LC
authors.lastname: Pereira
authors.forename: Luiz Felippe Cabral
authors.initials: LF
authors.lastname: Miranda
authors.forename: Alecsandra Oliveira
authors.initials: AO
authors.lastname: de Souza
authors.forename: Daniel Junqueira
authors.initials: DJ
authors.lastname: Dorta
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D011075:Polybrominated Biphenyls; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C533761:hexabromodiphenyl ether 154