Endosulfan sulfate is a major oxidative metabolite of the chlorinated insecticide endosulfan. In this study, a targeted metabolomics approach was used to investigate the toxic mechanisms of endosulfan sulfate in adult zebrafish using the multiple reaction monitoring mode of a GC-MS/MS. The LC50 of endosulfan sulfate in adult zebrafish was determined and then zebrafish were exposed to endosulfan sulfate at one-tenth the LC50 (0.1LC50) or the LC50 for 24 and 48 h. After exposure, the fish were extracted, derivatized and analyzed by GC-MS/MS for 379 metabolites to identify 170 metabolites. Three experimental groups (control, 0.1LC50 and LC50) were clearly separated in PLS-DA score plots. Based on the VIP, ANOVA, and fold change results, 40 metabolites were selected as biomarkers. Metabolic pathways associated with those metabolites were identified using MetaboAnalyst 4.0 as follows: aminoacyl-tRNA biosynthesis, valine/leucine/isoleucine biosynthesis, citrate cycle, glycerolipid metabolism, and arginine/proline metabolism. Gene expression studies confirmed the activation of citrate cycle and glycerolipids metabolism. MDA levels of the exposed group significantly increased in oxidative toxicity assay tests. Such significant perturbations of important metabolites within key biochemical pathways must result in biologically hazardous effects in zebrafish.

中文翻译：

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使用GC-MS / MS在多反应监测模式下对成年斑马鱼（Danio rerio）中的硫酸硫丹进行靶向毒理学研究。

硫酸硫丹是氯化杀虫硫丹的主要氧化代谢产物。在这项研究中，有针对性的代谢组学方法被用来使用GC-MS / MS的多反应监测模式研究成年斑马鱼中硫酸硫丹的毒性机制。确定成年斑马鱼中硫酸硫丹的LC50，然后将斑马鱼以十分之一的LC50（0.1LC50）或LC50暴露于硫酸硫丹24小时和48小时。暴露后，将鱼提取，衍生并通过GC-MS / MS分析379种代谢物，从而鉴定出170种代谢物。在PLS-DA评分图中将三个实验组（对照组，0.1LC50和LC50）明确分开。根据VIP，ANOVA和倍数变化结果，选择了40种代谢物作为生物标志物。使用MetaboAnalyst 4.0识别与这些代谢物相关的代谢途径如下：氨酰基-tRNA生物合成，缬氨酸/亮氨酸/异亮氨酸生物合成，柠檬酸盐循环，甘油脂代谢和精氨酸/脯氨酸代谢。基因表达研究证实了柠檬酸循环和甘油脂代谢的激活。在氧化毒性试验中，暴露组的MDA水平显着增加。关键生化途径中重要代谢物的如此显着扰动必须导致斑马鱼的生物危害作用。在氧化毒性试验中，暴露组的MDA水平显着增加。关键生化途径中重要代谢物的如此显着扰动必须导致斑马鱼的生物危害作用。在氧化毒性试验中，暴露组的MDA水平显着增加。关键生化途径中重要代谢物的这种显着扰动必须导致斑马鱼的生物危害作用。