Effect of marine omega 3 fatty acids on methylmercury-induced toxicity in fish and mammalian cells in vitro.
Methylmercury (MeHg) is a ubiquitous environmental contaminant which bioaccumulates in marine biota. Fish constitute an important part of a balanced human diet contributing with health beneficial nutrients but may also contain contaminants such as MeHg. Interactions between the marine n-3 fatty acids eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) with MeHg-induced toxicity were investigated. Different toxic and metabolic responses were studied in Atlantic salmon kidney (ASK) cell line and the mammalian kidney-derived HEK293 cell line. Both cell lines were preincubated with DHA or EPA prior to MeHg-exposure, and cell toxicity was assessed differently in the cell lines by MeHg-uptake in cells (ASK and HEK293), proliferation (HEK293 and ASK), apoptosis (ASK), oxidation of the red-ox probe roGFP (HEK293), and regulation of selected toxicological and metabolic transcriptional markers (ASK). DHA was observed to decrease the uptake of MeHg in HEK293, but not in ASK cells. DHA also increased, while EPA decreased, MeHg-induced apoptosis in ASK. MeHg exposure induced changes in selected metabolic and known MeHg biomarkers in ASK cells. Both DHA and MeHg, but not EPA, oxidized roGFP in HEK293 cells. In conclusion, marine n-3 fatty acids may ameliorate MeHg toxicity, either by decreasing apoptosis (EPA) or by reducing MeHg uptake (DHA). However, DHA can also augment MeHg toxicity by increasing oxidative stress and apoptosis when combined with MeHg.
National Institute of Nutrition and Research-NIFES, P.O. Box 2029 Nordnes, 5817 Bergen, Norway. ono@nifes.no
O J
OJ
Nøstbakken
I L
IL
Bredal
P A
PA
Olsvik
T S
TS
Huang
B E
BE
Torstensen
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide; D008767:Methylmercury Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012474:Salmon
D015525:Fatty Acids, Omega-3; D008767:Methylmercury Compounds; D011506:Proteins; D006861:Hydrogen Peroxide