US EPA

2819226 

Journal Article 

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

Yeh, A; Kruse, SE; Marcinek, DJ; Gallagher, EP 

2015 

1 

Toxicology In Vitro
ISSN: 0887-2333
EISSN: 1879-3177 

29 

4 

672-680 

English 

25659769 

10.1016/j.tiv.2015.01.015 

WOS:000353754400004 

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. 

Omega-3 polyunsaturated fatty acids; PBDE; BDE 47; Mitochondria; Salmon; Oxidative stress