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Toxicometabolomics of lindane in adult zebrafish (Danio rerio) using GC-MS/MS and LC-Orbitrap-MS/MS
Applied Biological Chemistry ( IF 3.2 ) Pub Date : 2021-07-16 , DOI: 10.1186/s13765-021-00623-4
Xiu Yuan 1 , Junghak Lee 1 , Eunyoung Park 1 , Jeong-Han Kim 1 , Hwa-Kyung Lee 2
Affiliation  

Lindane is a broad-spectrum persistent organochlorine pesticide that has been used to control pests for many years. In this study, its toxic mechanisms in adult zebrafish were investigated using targeted metabolomics with GC-MS/MS and non-targeted metabolomics with LC-Orbitrap-MS/MS. Zebrafish was exposed to lindane in water for 48 h in three groups: control, low exposure (1/10 LC50) and high exposure (LC50). In the zebrafish exposed to low concentration of lindane, 2.24–3.98 mg/kg of lindane were determined, while 35.67–56.46 mg/kg were observed in the zebrafish exposed to high concentration. A total of 118 metabolites were identified from 394 metabolites on GC-MS/MS and 45 metabolites were selected as biomarkers. A total of 62 metabolites were identified on LC-Orbitrap-MS/MS and 7 metabolites were selected as biomarkers. Three groups were well separated on partial least squares-discriminant analysis (PLS-DA), and a total of 52 metabolites in both the targeted and non-targeted metabolites were selected as biomarkers through VIP and ANOVA tests to construct a heatmap. Five metabolic pathways such as the pentose phosphate pathway (PPP), histidine metabolism, phenylalanine metabolism, alanine/aspartate/glutamate metabolism, and phenylalanine/tyrosine/tryptophan biosynthesis, were observed to show toxicologically significant alterations. Oxidative stress was also confirmed through MDA and ROS assays. Such perturbations of the metabolic pathways of zebrafish caused by the exposure to lindane resulted in significant toxicological effects.

中文翻译:

使用 GC-MS/MS 和 LC-Orbitrap-MS/MS 分析成年斑马鱼 ( Danio rerio )中林丹的毒物代谢组学

林丹是一种广谱持久性有机氯农药,多年来一直用于防治害虫。在这项研究中,使用带有 GC-MS/MS 的靶向代谢组学和带有 LC-Orbitrap-MS/MS 的非靶向代谢组学研究了其在成年斑马鱼中的毒性机制。斑马鱼在三组中暴露于水中的林丹 48 小时:对照组、低暴露 (1/10 LC50) 和高暴露 (LC50)。在暴露于低浓度林丹的斑马鱼中,测定了 2.24–3.98 mg/kg 的林丹,而在暴露于高浓度林丹的斑马鱼中观察到了 35.67–56.46 mg/kg。GC-MS/MS 从 394 种代谢物中鉴定出总共 118 种代谢物,并选择 45 种代谢物作为生物标志物。在 LC-Orbitrap-MS/MS 上共鉴定了 62 种代谢物,并选择了 7 种代谢物作为生物标志物。在偏最小二乘判别分析(PLS-DA)上将三组很好地分开,通过VIP和ANOVA测试从靶向和非靶向代谢物中总共选择52种代谢物作为生物标志物以构建热图。观察到五种代谢途径,如磷酸戊糖途径 (PPP)、组氨酸代谢、苯丙氨酸代谢、丙氨酸/天冬氨酸/谷氨酸代谢和苯丙氨酸/酪氨酸/色氨酸生物合成,显示出毒理学上的显着变化。氧化应激也通过 MDA 和 ROS 测定得到证实。由暴露于林丹引起的斑马鱼代谢途径的这种扰动导致了显着的毒理学效应。并通过VIP和ANOVA测试选择靶向和非靶向代谢物中的52种代谢物作为生物标志物构建热图。观察到五种代谢途径,如磷酸戊糖途径 (PPP)、组氨酸代谢、苯丙氨酸代谢、丙氨酸/天冬氨酸/谷氨酸代谢和苯丙氨酸/酪氨酸/色氨酸生物合成,显示出毒理学上的显着变化。氧化应激也通过 MDA 和 ROS 测定得到证实。由暴露于林丹引起的斑马鱼代谢途径的这种扰动导致了显着的毒理学效应。并通过VIP和ANOVA测试选择靶向和非靶向代谢物中的52种代谢物作为生物标志物构建热图。观察到五种代谢途径,如磷酸戊糖途径 (PPP)、组氨酸代谢、苯丙氨酸代谢、丙氨酸/天冬氨酸/谷氨酸代谢和苯丙氨酸/酪氨酸/色氨酸生物合成,显示出毒理学上的显着变化。氧化应激也通过 MDA 和 ROS 测定得到证实。由暴露于林丹引起的斑马鱼代谢途径的这种扰动导致了显着的毒理学效应。观察到丙氨酸/天冬氨酸/谷氨酸代谢和苯丙氨酸/酪氨酸/色氨酸生物合成显示出毒理学上的显着变化。氧化应激也通过 MDA 和 ROS 测定得到证实。由暴露于林丹引起的斑马鱼代谢途径的这种扰动导致了显着的毒理学效应。观察到丙氨酸/天冬氨酸/谷氨酸代谢和苯丙氨酸/酪氨酸/色氨酸生物合成显示出毒理学上的显着变化。氧化应激也通过 MDA 和 ROS 测定得到证实。由暴露于林丹引起的斑马鱼代谢途径的这种扰动导致了显着的毒理学效应。
更新日期:2021-07-16
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