Effect of omega-3 fatty acid oxidation products on the cellular and mitochondrial toxicity of BDE 47

• Published in: Toxicology in vitro 2015-06, Vol.29 (4), p.672-680
• Main Authors: Yeh, Andrew, Kruse, Shane E., Marcinek, David J., Gallagher, Evan P.
• Format: Article
• Language: English
• Subjects: BDE 47; Cell Line, Tumor; Electron Transport - drug effects; Fatty Acids, Omega-3 - pharmacology; Flame Retardants - toxicity; Glutathione - metabolism; Halogenated Diphenyl Ethers - toxicity; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Omega-3 polyunsaturated fatty acids; Oxidation-Reduction; Oxidative Stress; PBDE; Reactive Oxygen Species - metabolism; Salmon; Salmonidae
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2015.01.015

•BDE 47 is a toxic PBDE flame retardant and major contaminant in Pacific salmon.•Oxidized omega-3 fatty acids (oxEPA/oxDHA) partially prevented BDE 47 toxicity.•oxEPA/oxDHA partially protected viability and mitochondrial membrane potential.•oxEPA/oxDHA partially protected mitochondrial electron transport system function.•Our results indicate oxEPA/oxDHA protects against shorter exposures to BDE 47. 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 100μM BDE 47. Pretreatment with oxEPA/oxDHA for 12h 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.