Olsvik Pål A, Søfteland Liv
Nord University, Faculty of Biosciences and Aquaculture, Bodø, Norway.
Institute of Marine Research (IMR), Bergen, Norway.
Toxicol Rep. 2020 Apr 6;7:547-558. doi: 10.1016/j.toxrep.2020.03.008. eCollection 2020.
Pesticide formulations typically contain adjuvants added to enhance the performance of the active ingredient. Adjuvants may modify the bioavailability and toxicity of pesticides. In this study, the aim was to examine to which degree nonylphenol (NP) may interfere with the toxicity of two organophosphorus pesticides found in aquafeeds, chlorpyrifos-methyl (CPM) and pirimiphos-methyl (PPM). Atlantic salmon liver cells were exposed to these compounds singly or in combinations for 48 h using 3D cell cultures. Cytotoxicity, gene expression (RT-qPCR), and lipidomics endpoints were used to assess toxicity. The dose-response assessment showed that NP was the most toxic compound at equimolar concentrations (100 μM). Shotgun lipidomics pointed to a general pattern of elevated levels of saturated 18:0 fatty acids and declined levels of 18:1 monounsaturated fatty acids by the combined treatment. All three compounds had a distinct effect on membrane phospholipids, in particular on phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Lipid species patterns predicted inhibited stearoyl CoA desaturase (SCD) activity and increased Δ6 desaturase (D6D) activity in co-treated cells. While all three compounds alone mitigated increased triacylglycerol (TAG) accumulation, combined treatment resulted in lower total TAG in the cells. Multivariate analysis with PLS regression showed significant combined effects for nine genes (, , , , , , , and ) and four lipid species (FFA 22:5, LPC 18:0, TAG52:1-FA16:0, and TAG52:1-FA18:0). In summary, this study demonstrates that the adjuvant can be the main contributor to the toxicity of a mixture of two organophosphorus pesticides with relatively low toxicity in fish cells.
农药制剂通常含有添加的助剂，以增强活性成分的性能。助剂可能会改变农药的生物利用度和毒性。在本研究中，目的是考察壬基酚（NP）在何种程度上可能干扰水产饲料中发现的两种有机磷农药，即甲基毒死蜱（CPM）和甲基嘧啶磷（PPM）的毒性。使用3D细胞培养将大西洋鲑鱼肝细胞单独或组合暴露于这些化合物48小时。细胞毒性、基因表达（RT-qPCR）和脂质组学终点用于评估毒性。剂量反应评估表明，在等摩尔浓度（100μM）下，NP是毒性最大的化合物。鸟枪法脂质组学指出，联合处理导致饱和18:0脂肪酸水平普遍升高，18:1单不饱和脂肪酸水平下降。所有三种化合物对膜磷脂都有显著影响，特别是对磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）。脂质种类模式预测，联合处理的细胞中硬脂酰辅酶A去饱和酶（SCD）活性受到抑制，Δ6去饱和酶（D6D）活性增加。虽然所有三种化合物单独使用都能减轻三酰甘油（TAG）积累的增加，但联合处理导致细胞中总TAG含量降低。使用PLS回归的多变量分析显示，九个基因（、、、、、、、和）和四种脂质种类（FFA 22:5、LPC 18:0、TAG52:1-FA16:0和TAG52:1-FA18:0）存在显著的联合效应。总之，本研究表明，助剂可能是鱼类细胞中两种毒性相对较低的有机磷农药混合物毒性的主要贡献者。
