Marine fatty acids aggravate hepatotoxicity of α-HBCD in juvenile female BALB/c mice

Annette Bernhard; Marc H G Berntssen; Anne-Katrine Lundebye; Anita Røyneberg Alvheim; Lene Secher Myrmel; Even Fjære; Bente E Torstensen; Karsten Kristiansen; Lise Madsen; Trond Brattelid; Josef D Rasinger

doi:10.1016/j.fct.2016.10.002

Marine fatty acids aggravate hepatotoxicity of α-HBCD in juvenile female BALB/c mice

Food Chem Toxicol. 2016 Nov:97:411-423. doi: 10.1016/j.fct.2016.10.002. Epub 2016 Oct 4.

Affiliations

¹ 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.
² National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: marc.berntssen@nifes.no.
³ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: anne-katrine.lundebye@nifes.no.
⁴ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: Anita.Royneberg.Alvheim@hib.no.
⁵ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: lenesecher.myrmel@nifes.no.
⁶ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: even.fjaere@nifes.no.
⁷ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: bente.torstensen@marineharvest.no.
⁸ Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark. Electronic address: kk@bio.ku.dk.
⁹ 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.
¹⁰ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: trond.brattelid@hib.no.
¹¹ National Institute of Nutrition and Seafood Research (NIFES), P.O.BOX 2029 Nordnes, N-5817 Bergen, Norway. Electronic address: josef.rasinger@nifes.no.

PMID: 27717803
DOI: 10.1016/j.fct.2016.10.002

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.

Keywords: Hexabromocyclododecane; Juvenile toxicity; Marine fatty acids; Nutritional modulation.

MeSH terms

Animals
Diet / adverse effects*
Dose-Response Relationship, Drug
Fatty Acids / toxicity*
Female
Food Contamination / analysis
Gene Expression Regulation / drug effects
Hydrocarbons, Brominated / toxicity*
Liver / drug effects*
Liver / metabolism
Mice
Mice, Inbred BALB C
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Seafood

Substances

Fatty Acids
Hydrocarbons, Brominated
RNA, Messenger
hexabromocyclododecane