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免疫反应对德尔塔氯氰菊酯在早期生命阶段斑马鱼心脏毒性和肝毒性的贡献()。

Contribution of Immune Responses to the Cardiotoxicity and Hepatotoxicity of Deltamethrin in Early Life Stage Zebrafish ().

机构信息

Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, P. R. China.

Department of Environmental Sciences,University of California, Riverside, California 92521, United States.

出版信息

Environ Sci Technol. 2024 Jun 4;58(22):9515-9524. doi: 10.1021/acs.est.3c10682. Epub 2024 Apr 30.

Abstract

Deltamethrin (DM) is a widely used insecticide that has demonstrated developmental toxicity in the early life stages of fish. To better characterize the underlying mechanisms, embryos from Tg(cmlc2:RFP), Tg(apo14:GFP), and Tg(mpx:GFP) transgenic strains of zebrafish were exposed to nominal DM concentrations of 0.1, 1, 10, 25, and 50 μg/L until 120 h post-fertilization (hpf). Heart size increased 56.7%, and liver size was reduced by 17.1% in zebrafish exposed to 22.7 and 24.2 μg/L DM, respectively. RNA sequencing and bioinformatic analyses predicted that key biological processes affected by DM exposure were related to inflammatory responses. Expression of IL-1 protein was increased by 69.0% in the 24.4 μg/L DM treatment, and aggregation of neutrophils in cardiac and hepatic histologic sections was also observed. Coexposure to resatorvid, an anti-inflammatory agent, mitigated inflammatory responses and cardiac toxicity induced by DM and also restored liver biomass. Our data indicated a complex proinflammatory mechanism underlying DM-induced cardiotoxicity and hepatotoxicity which may be important for key events of adverse outcomes and associated risks of DM to early life stages of fish.

摘要

溴氰菊酯(DM)是一种广泛使用的杀虫剂,已在鱼类的早期生命阶段证明具有发育毒性。为了更好地描述潜在的机制,用名义 DM 浓度为 0.1、1、10、25 和 50μg/L 处理 Tg(cmlc2:RFP)、Tg(apo14:GFP)和 Tg(mpx:GFP)三种斑马鱼转基因系的胚胎,直到受精后 120 小时(hpf)。暴露于 22.7 和 24.2μg/L DM 的斑马鱼心脏大小分别增加了 56.7%,肝脏大小减少了 17.1%。RNA 测序和生物信息学分析预测,受 DM 暴露影响的关键生物过程与炎症反应有关。在 24.4μg/L DM 处理中,IL-1 蛋白的表达增加了 69.0%,并且在心脏和肝脏组织学切片中也观察到中性粒细胞的聚集。与抗炎症剂瑞他莫司共暴露减轻了 DM 引起的炎症反应和心脏毒性,并恢复了肝生物量。我们的数据表明,DM 诱导的心脏毒性和肝毒性的潜在机制是复杂的促炎机制,这对于 DM 对鱼类早期生命阶段的不良后果和相关风险的关键事件可能很重要。

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