title: Low concentrations of the brominated flame retardants BDE-47 and BDE-99 induce synergistic oxidative stress-mediated neurotoxicity in human neuroblastoma cells.
abstract: Polybrominated diphenyl ether (PBDE) flame retardants have become widespread environmental contaminants. The highest body burden has been found in toddlers and infants, due to their exposure through breast milk and house dust, and the current concern for potential adverse health effects of PBDEs relates to their developmental neurotoxicity. The mechanisms underlying the neurotoxicity of PBDEs are largely not understood, though there is evidence that PBDEs may elicit oxidative stress. In this study, two different mathematical models were used to evaluate the interaction between BDE-47 and BDE-99 on viability of neuronal cells. The combined exposure to these compounds induced synergistic effects at concentrations of BDE-47 below its threshold doses, and in a wide range of BDE-99 concentrations below its IC(50). In contrast, at concentrations of BDE-47 near its IC(50) value, and in a wide range of BDE-99 concentrations, antagonistic effects were observed. The interactions observed on cell viability were confirmed by an assessment of induction of oxidative stress. The finding that co-exposure to BDE-47 and BDE-99 could induce synergistic neurotoxic effects, in particular at low doses of BDE-47, is of much toxicological interest, as humans are exposed to mixtures of PBDEs, most notably tetra- and penta-BDE congeners.
authors.affiliation: Dept. of Human Anatomy, Pharmacology, and Forensic Science, University of Parma, Parma, Italy. sara.tagliaferri@nemo.unipr.it
authors.forename: Sara
authors.initials: S
authors.lastname: Tagliaferri
authors.forename: Andrea
authors.initials: A
authors.lastname: Caglieri
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.forename: Diana
authors.initials: D
authors.lastname: Poli
authors.forename: Claudia
authors.initials: C
authors.lastname: Pellacani
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giordano
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
authors.forename: Lucio G
authors.initials: LG
authors.lastname: Costa
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D015233:Models, Statistical; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014343:Trypan Blue
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances; C511295:2,2',4,4'-tetrabromodiphenyl ether; C022616:thiazolyl blue; D014343:Trypan Blue