Søfteland Liv, Berntssen Marc H G, Kirwan Jennifer A, Størseth Trond R, Viant Mark R, Torstensen Bente E, Waagbø Rune, Olsvik Pål A
National Institute of Nutrition and Seafood Research, Norway.
School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
Toxicol Rep. 2016 Jan 14;3:211-224. doi: 10.1016/j.toxrep.2016.01.008. eCollection 2016.
Extended use of plant ingredients in Atlantic salmon farming has increased the need for knowledge on the effects of new nutrients and contaminants in plant based feeds on fish health and nutrient-contaminant interactions. Primary Atlantic salmon hepatocytes were exposed to a mixture of PAHs and pesticides alone or in combination with the nutrients ARA, EPA, α-tocopherol, and γ-tocopherol according to a factorial design. Cells were screened for effects using xCELLigence cytotoxicity screening, NMR spectroscopy metabolomics, mass spectrometry lipidomics and RT-qPCR transcriptomics. The cytotoxicity results suggest that adverse effects of the contaminants can be counteracted by the nutrients. The lipidomics suggested effects on cell membrane stability and vitamin D metabolism after contaminant and fatty acid exposure. Co-exposure of the contaminants with EPA or α-tocopherol contributed to an antagonistic effect in exposed cells, with reduced effects on the VTG and FABP4 transcripts. ARA and γ-tocopherol strengthened the contaminant-induced response, ARA by contributing to an additive and synergistic induction of CYP1A, CYP3A and CPT2, and γ-tocopherol by synergistically increasing ACOX1. Individually EPA and α-tocopherol seemed more beneficial than ARA and γ-tocopherol in preventing the adverse effects induced by the contaminant mixture, though a combination of all nutrients showed the greatest ameliorating effect.
在大西洋鲑鱼养殖中对植物成分的广泛使用,增加了对植物性饲料中新型营养物质和污染物对鱼类健康及营养物质 - 污染物相互作用影响的知识需求。根据析因设计,将原代大西洋鲑鱼肝细胞单独或与营养物质花生四烯酸(ARA)、二十碳五烯酸(EPA)、α - 生育酚和γ - 生育酚联合暴露于多环芳烃(PAHs)和农药的混合物中。使用xCELLigence细胞毒性筛选、核磁共振光谱代谢组学、质谱脂质组学和逆转录 - 定量聚合酶链反应转录组学对细胞进行效应筛选。细胞毒性结果表明,营养物质可以抵消污染物的不利影响。脂质组学表明,污染物和脂肪酸暴露后对细胞膜稳定性和维生素D代谢有影响。污染物与EPA或α - 生育酚共同暴露对暴露细胞产生拮抗作用,对卵黄蛋白原(VTG)和脂肪酸结合蛋白4(FABP4)转录本的影响降低。ARA和γ - 生育酚增强了污染物诱导的反应,ARA通过对细胞色素P450 1A(CYP1A)、细胞色素P450 3A(CYP3A)和肉碱棕榈酰转移酶2(CPT2)产生累加和协同诱导作用,γ - 生育酚通过协同增加酰基辅酶A氧化酶1(ACOX1)来增强。单独来看,EPA和α - 生育酚在预防污染物混合物诱导的不利影响方面似乎比ARA和γ - 生育酚更有益,尽管所有营养物质组合显示出最大的改善效果。