title: Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.
abstract: Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 μM to 50 μM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lílian Cristina
authors.initials: LC
authors.lastname: Pereira
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 / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005411:Flame Retardants; D011075:Polybrominated Biphenyls; C517827:pentabrominated diphenyl ether 100; D000255:Adenosine Triphosphate; D002118:Calcium