The aim of the present study was to investigate effects of defined mixtures of polycyclic aromatic hydrocarbons (PAHs) and perfluoroalkyl substances (PFASs), at low, environmentally relevant (1× = L), or high (20× = H) doses, on biological responses in Atlantic cod (Gadus morhua). To this end, farmed juvenile cod were exposed at day 0 and day 7 via intraperitoneal (i.p.) injections, in a two-week in vivo experiment. In total, there were 10 groups of fish (n = 21-22): two control groups, four separate exposure groups of PAH and PFAS mixtures (L, H), and four groups combining PAH and PFAS mixtures (L/L, H/L, L/H, H/H). Body burden analyses confirmed a dose-dependent accumulation of PFASs in cod liver and PAH metabolites in bile. The hepatosomatic index (HSI) was significantly reduced for three of the combined PAH/PFAS exposure groups (L-PAH/H-PFAS, H-PAH/L-PFAS, H-PAH/H-PFAS). Analysis of the hepatic proteome identified that pathways related to lipid degradation were significantly affected by PFAS exposure, including upregulation of enzymes in fatty acid degradation pathways, such as fatty acid β-oxidation. The increased abundances of enzymes in lipid catabolic pathways paralleled with decreasing levels of triacylglycerols (TGs) in the H-PFAS exposure group, suggest that PFAS increase lipid catabolism in Atlantic cod. Markers of oxidative stress, including catalase and glutathione S-transferase activities were also induced by PFAS exposure. Only minor and non-significant differences between exposure groups and control were found for cyp1a and acox1 gene expressions, vitellogenin concentrations in plasma, Cyp1a protein synthesis and DNA fragmentation. In summary, our combined proteomics and lipidomics analyses indicate that PFAS may disrupt lipid homeostasis in Atlantic cod.

本研究的目的是研究在低，与环境相关（1×= L）或高（20×= H）剂量下，多环芳烃（PAH）和全氟烷基物质（PFAS）的确定混合物对大西洋鳕（Gadus morhua）的生物学反应。为此，在两周的体内第0天和第7天通过腹膜内（ip）注射养殖的鳕鱼实验。总共有10组鱼（n = 21-22）：两个对照组，四个单独的PAH和PFAS混合物（L，H）暴露组，以及四个结合PAH和PFAS混合物（L / L，H）的组/ L，L / H，H / H）。身体负担分析证实了鳕鱼肝中PFAS和胆汁中PAH代谢产物的剂量依赖性积累。对于三个PAH / PFAS联合暴露组（L-PAH / H-PFAS，H-PAH / L-PFAS，H-PAH / H-PFAS），肝体指数（HSI）显着降低。对肝蛋白质组的分析表明，与脂质降解相关的途径受PFAS暴露的影响很大，包括脂肪酸降解途径中的酶上调，例如脂肪酸β-氧化。在H-PFAS暴露组中，脂质分解代谢途径中酶的丰度增加与三酰基甘油（TGs）含量的降低平行，表明PFAS在大西洋鳕鱼中增加了脂质分解代谢。PFAS暴露也诱导了氧化应激的标志物，包括过氧化氢酶和谷胱甘肽S-转移酶活性。仅发现暴露组与对照组之间的微小差异和非显着差异cyp1a和acox1基因表达，血浆卵黄蛋白原浓度，Cyp1a蛋白合成和DNA片段化。总之，我们结合蛋白质组学和脂质组学分析表明，PFAS可能会破坏大西洋鳕鱼的脂质稳态。