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螺虫乙酯诱导成年斑马鱼(Danio rerio)肝损伤及脂质代谢紊乱

Liver damage and lipid metabolic dysregulation in adult zebrafish (Danio rerio) induced by spirotetramat.

机构信息

Key Laboratory for Biology of Crop Pathogens and Insect Pests and Their Ecological Regulation of Zhejiang Province, College of Advanced Agricultural Sciences, Zhejiang A & F University, Hangzhou 311300, China; Key Laboratory of Microbial Control Technology for Industrial Pollution in Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, China.

Key Laboratory for Biology of Crop Pathogens and Insect Pests and Their Ecological Regulation of Zhejiang Province, College of Advanced Agricultural Sciences, Zhejiang A & F University, Hangzhou 311300, China.

出版信息

Sci Total Environ. 2024 Nov 15;951:175525. doi: 10.1016/j.scitotenv.2024.175525. Epub 2024 Aug 13.

DOI:10.1016/j.scitotenv.2024.175525
PMID:39147054
Abstract

Spirotetramat, an insecticide derived from cycloketone and extensively utilized in agricultural production, has been reported to be toxic to an array of aquatic organisms. Previous studies have indicated that spirotetramat can cause toxicity such as impaired ovarian development and apoptosis in zebrafish, but its toxicological effects on lipid metabolism and liver health in zebrafish remain unclear. In this study, we explored the effects of spirotetramat exposure on zebrafish (Danio rerio) by examining key markers of lipid metabolism, alterations in gene expression related to this process, and histological characteristics of the liver. Spirotetramat significantly reduced the condition factor, triglycerides and low-density lipoprotein cholesterol levels at 2 mg/L. The expression of genes related to fatty acid synthesis (acacb), β-oxidation (acox1, pparda) and pro-inflammatory cytokines (tnf-α, il-1β) was downregulated. However, the expression of genes related to lipid transport and uptake (cd36, ppara) and output (apob) was upregulated. The activity of alanine aminotransferase was significantly inhibited. Histopathology results showed that spirotetramat exposure led to liver cell vacuolation and necrosis. In addition, molecular docking results of spirotetramat and lipid transport related protein (ACC, ApoB) in both zebrafish and human showed the binding energy of human proteins is lower than that for zebrafish, and that the number of hydrogen bonds formed was higher. It is speculated that spirotetramat may also pose a significant potential hazard to humans, potentially affecting human lipid metabolism and health. This study expunge shed light on the ecological toxicity of spirotetramat by showing how it disrupts lipid metabolism and causes tissue damage specifically in zebrafish liver, contributing to a deeper understanding of its harmful effects in aquatic environment.

摘要

螺虫乙酯是一种由环己酮衍生而来的杀虫剂,广泛应用于农业生产中,据报道对多种水生生物具有毒性。先前的研究表明,螺虫乙酯可导致斑马鱼卵巢发育受损和细胞凋亡等毒性,但它对斑马鱼脂质代谢和肝脏健康的毒理学影响尚不清楚。在这项研究中,我们通过检查脂质代谢的关键标志物、与该过程相关的基因表达的变化以及肝脏的组织学特征,探讨了螺虫乙酯暴露对斑马鱼(Danio rerio)的影响。螺虫乙酯在 2mg/L 时显著降低了条件系数、甘油三酯和低密度脂蛋白胆固醇水平。脂肪酸合成(acacb)、β-氧化(acox1、pparda)和促炎细胞因子(tnf-α、il-1β)相关基因的表达下调。然而,与脂质转运和摄取(cd36、ppara)和输出(apob)相关的基因表达上调。丙氨酸氨基转移酶的活性显著受到抑制。组织病理学结果表明,螺虫乙酯暴露导致肝细胞空泡化和坏死。此外,螺虫乙酯与脂质转运相关蛋白(ACC、ApoB)在斑马鱼和人类中的分子对接结果表明,人类蛋白的结合能低于斑马鱼,形成的氢键数量更高。推测螺虫乙酯可能对人类也构成重大潜在危害,可能影响人类脂质代谢和健康。本研究通过展示螺虫乙酯如何特异性破坏斑马鱼肝脏的脂质代谢并导致组织损伤,揭示了其对生态的毒性,有助于深入了解其在水生环境中的有害影响。

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