title: Marine fatty acids aggravate hepatotoxicity of α-HBCD in juvenile female BALB/c mice.
abstract: Oily fish, a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), may contain persistent organic pollutants (POPs), including α-hexabromocyclododecane (α-HBCD). In experimental studies, marine LC n-3 PUFAs ameliorate fatty liver development while HBCD exposure was found to cause liver fatty acid (FA) changes. The present study investigated interactions of FAs and α-HBCD in juvenile female BALB/c mice using a factorial design. Mice (n = 48) were exposed for 28 days to a low (100 μg*kg body weight (BW)-1*day-1) or high dose (100 mg*kg BW-1*day-1) of α-HBCD in diets with or without LC n-3 PUFAs. High dose α-HBCD affected whole body lipid metabolism leading to changes in body weight and composition, and pathological changes in hepatic histology, which surprisingly were aggravated by dietary LC n-3 PUFAs. Hepatic FA profiling and gene expression analysis indicated that the dietary modulation of the hepatotoxic response to the high dose of α-HBCD was associated with differential effects on FA β-oxidation. Our results suggest that in a juvenile mouse model, marine FAs accentuate hepatotoxic effects of high dose α-HBCD. This highlights that the background diet is a critical variable in the risk assessment of POPs and warrants further investigation of dietary mediated toxicity of food contaminants.
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark. Electronic address: annette.bernhard@nifes.no.
authors.forename: Annette
authors.initials: A
authors.lastname: Bernhard
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: marc.berntssen@nifes.no.
authors.forename: Marc H G
authors.initials: MH
authors.lastname: Berntssen
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: anne-katrine.lundebye@nifes.no.
authors.forename: Anne-Katrine
authors.initials: AK
authors.lastname: Lundebye
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: Anita.Royneberg.Alvheim@hib.no.
authors.forename: Anita
authors.initials: A
authors.lastname: Røyneberg Alvheim
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: lenesecher.myrmel@nifes.no.
authors.forename: Lene
authors.initials: L
authors.lastname: Secher Myrmel
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: even.fjaere@nifes.no.
authors.forename: Even
authors.initials: E
authors.lastname: Fjære
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: bente.torstensen@marineharvest.no.
authors.forename: Bente E
authors.initials: BE
authors.lastname: Torstensen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark. Electronic address: kk@bio.ku.dk.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark. Electronic address: lise.madsen@nifes.no.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: trond.brattelid@hib.no.
authors.forename: Trond
authors.initials: T
authors.lastname: Brattelid
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: josef.rasinger@nifes.no.
authors.forename: Josef D
authors.initials: JD
authors.lastname: Rasinger
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000633:toxicity*; D005260:Female; D005506:Food Contamination / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017747:Seafood
chemical_list: D005227:Fatty Acids; D006842:Hydrocarbons, Brominated; D012333:RNA, Messenger; C089796:hexabromocyclododecane
keywords: Hexabromocyclododecane; Juvenile toxicity; Marine fatty acids; Nutritional modulation