PMID- 27717803 OWN - NLM STAT- MEDLINE DCOM- 20170309 LR - 20170309 IS - 1873-6351 (Electronic) IS - 0278-6915 (Linking) VI - 97 DP - 2016 Nov TI - Marine fatty acids aggravate hepatotoxicity of alpha-HBCD in juvenile female BALB/c mice. PG - 411-423 LID - S0278-6915(16)30352-0 [pii] LID - 10.1016/j.fct.2016.10.002 [doi] AB - Oily fish, a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), may contain persistent organic pollutants (POPs), including alpha-hexabromocyclododecane (alpha-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 alpha-HBCD in juvenile female BALB/c mice using a factorial design. Mice (n = 48) were exposed for 28 days to a low (100 mug*kg body weight (BW)(-1)*day(-1)) or high dose (100 mg*kg BW(-1)*day(-1)) of alpha-HBCD in diets with or without LC n-3 PUFAs. High dose alpha-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 alpha-HBCD was associated with differential effects on FA beta-oxidation. Our results suggest that in a juvenile mouse model, marine FAs accentuate hepatotoxic effects of high dose alpha-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. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Bernhard, Annette AU - Bernhard A AD - 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. FAU - Berntssen, Marc H G AU - Berntssen MH AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: marc.berntssen@nifes.no. FAU - Lundebye, Anne-Katrine AU - Lundebye AK AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: anne-katrine.lundebye@nifes.no. FAU - Royneberg Alvheim, Anita AU - Royneberg Alvheim A AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: Anita.Royneberg.Alvheim@hib.no. FAU - Secher Myrmel, Lene AU - Secher Myrmel L AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: lenesecher.myrmel@nifes.no. FAU - Fjaere, Even AU - Fjaere E AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: even.fjaere@nifes.no. FAU - Torstensen, Bente E AU - Torstensen BE AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: bente.torstensen@marineharvest.no. FAU - Kristiansen, Karsten AU - Kristiansen K AD - Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark. Electronic address: kk@bio.ku.dk. FAU - Madsen, Lise AU - Madsen L AD - 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. FAU - Brattelid, Trond AU - Brattelid T AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: trond.brattelid@hib.no. FAU - Rasinger, Josef D AU - Rasinger JD AD - National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: josef.rasinger@nifes.no. LA - eng PT - Journal Article DEP - 20161004 PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 0 (Fatty Acids) RN - 0 (Hydrocarbons, Brominated) RN - 0 (RNA, Messenger) RN - 5I9835JO3M (hexabromocyclododecane) SB - IM MH - Animals MH - Diet/*adverse effects MH - Dose-Response Relationship, Drug MH - Fatty Acids/*toxicity MH - Female MH - Food Contamination/analysis MH - Gene Expression Regulation/drug effects MH - Hydrocarbons, Brominated/*toxicity MH - Liver/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Seafood OTO - NOTNLM OT - Hexabromocyclododecane OT - Juvenile toxicity OT - Marine fatty acids OT - Nutritional modulation EDAT- 2016/10/30 06:00 MHDA- 2017/03/10 06:00 CRDT- 2016/10/09 06:00 PHST- 2016/05/27 00:00 [received] PHST- 2016/09/29 00:00 [revised] PHST- 2016/10/02 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2017/03/10 06:00 [medline] PHST- 2016/10/09 06:00 [entrez] AID - S0278-6915(16)30352-0 [pii] AID - 10.1016/j.fct.2016.10.002 [doi] PST - ppublish SO - Food Chem Toxicol. 2016 Nov;97:411-423. doi: 10.1016/j.fct.2016.10.002. Epub 2016 Oct 4.