title: Effect of omega-3 fatty acid oxidation products on the cellular and mitochondrial toxicity of BDE 47.
abstract: High levels of the flame retardant 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) have been detected in Pacific salmon sampled near urban areas, raising concern over the safety of salmon consumption. However, salmon fillets also contain the antioxidants eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), whose oxidation products induce cellular antioxidant responses. Because oxidative stress is a mechanism of BDE 47 toxicity, we hypothesized that oxidized EPA and DHA can ameliorate the cellular and mitochondrial toxicity of BDE 47. HepG2 cells were treated with a mixture of oxidized EPA and DHA (oxEPA/oxDHA) at a ratio relevant to salmon consumption (1.5/1 oxEPA/oxDHA) followed by exposure to 100 μM BDE 47. Pretreatment with oxEPA/oxDHA for 12 h prior to BDE 47 exposure prevented BDE 47-mediated depletion of glutathione, and increased expression of antioxidant response genes. oxEPA/oxDHA also reduced the level of reactive oxygen species production by BDE 47. The oxEPA/oxDHA antioxidant responses were associated with partial protection against BDE 47-induced loss of viability and also mitochondrial membrane potential. Mitochondrial electron transport system functional analysis revealed extensive inhibition of State 3 respiration and maximum respiratory capacity by BDE 47 were partially reversed by oxEPA/oxDHA. Our findings indicate that the antioxidant effects of oxEPA/oxDHA protect against short exposures to BDE 47, including a protective role of these compounds on maintaining cellular and mitochondrial function.
authors: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105-6099, United States.
authors: Andrew
authors: A
authors: Yeh
authors: Department of Radiology, University of Washington Medical School, Seattle, WA 98195, United States.
authors: Shane E
authors: SE
authors: Kruse
authors: Department of Radiology, University of Washington Medical School, Seattle, WA 98195, United States.
authors: David J
authors: DJ
authors: Marcinek
authors: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105-6099, United States. Electronic address: evang3@u.washington.edu.
authors: Evan P
authors: EP
authors: Gallagher
mesh_terms: D045744:Cell Line, Tumor; D004579:Electron Transport / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005411:Flame Retardants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D017382:Reactive Oxygen Species; C511295:2,2',4,4'-tetrabromodiphenyl ether; D005978:Glutathione
keywords: BDE 47; Mitochondria; Omega-3 polyunsaturated fatty acids; Oxidative stress; PBDE; Salmon