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Metal/Metal Oxide Nanomaterials and Oxidative Stress- Are there Harmful Health Effects in Fish for Environmental Exposures?

金属/金属氧化物纳米材料和氧化应激 - 鱼类暴露于环境中是否会对健康产生有害影响？

基本信息

批准号：
NE/L007371/1
负责人：
Charles Tyler
金额：
$ 52.16万
依托单位：
UNIVERSITY OF EXETER
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FL007371%2F1
关键词：
Metal Oxide Nanomaterials Oxidative Stress

项目摘要

The nanotechnology industry is worth $ billions to the global economy. Unique properties (e.g. surface reactivity) exhibited at the nanoscale (particles with at least one dimension less than 100nm) and exploited for use in these industries, however, can result in toxic properties and there is increasing experimental evidence for this. From a mechanistic perspective the ability to generate reactive oxygen species (ROS) and induce oxidative stress is increasingly being recognized as a paradigm to explain some of the toxic effects related to the particle for metal/metal oxide nanomaterials [NMs]. In this project we will undertake exposures of fish models to some of the most widely used and commercially important NMs, silver (Ag) and cerium oxide (CeO2), and investigate environmentally realistic scenarios to identify potentially harmful health effects via oxidative stress. This work will be enhanced greatly by the ability to detect, quantify and characterise NMs in complex environmental media and organisms at ambient levels, through the use of NMs that are labelled with highly enriched stable isotopes, advanced imaging methods (e.g. Coherent Antistoke Raman Scattering) and the development of a novel biosensor zebrafish model.A biosensor zebrafish will be developed with a convenient response system for detecting oxidative stress. In the zebrafish model, ROS triggers an electrophile responsive element (EpRE) reporter - normally found in the 'starter' (promoter) sequences of genes involved in protecting the cell from oxidative damage - and this will induce a green fluorescent protein (GFP) that can be detected via imaging. The genetic approach to develop this new biosensor fish has been applied successfully at Exeter for other pollutants. The model will enable identification of the target tissues for oxidative responses in real time. Transcriptomics - measuring the responses of many thousands of genes - will be used to identify the effect mechanisms (molecular pathways) in the responsive (green glowing) tissues for selected NM exposures. Findings from the studies with transgenic zebrafish will inform a NM exposure in a natural water with a fish species native to UK rivers (carp) to assess for chronic health in a partnership with South West Water. Detailed characterisation of the particles in the water will be undertaken to inform on particle fate and behaviour and help inform on their availability for uptake into fish. This project will build upon the significant track records and publications of the interdisciplinary team, bringing together extensive infrastructure and technological capability, and industry partnerships, to advance understanding on the potential for commercially important NMs to induce harm under realistic environmental conditions. The work will support NM risk assessment for both protection of the freshwater aquatic environment and sustainable development of the nanotech industry. All data generated will be published in the peer reviewed literature, in leading journals, and disseminated via public fora and liaison groups to stakeholders (e.g. public, regulators, industry), with which the partners have extensive existing links. The project proposed is directly relevant to NERC's science themes for Biodiversity, Sustainable use of natural resources and Environment, Pollution and Human health, and also to the EC European Water framework Directive - to develop our understanding of the environmental risks and hazards of pollution and wastes. The project furthermore supports the objectives of NERC's mission to promote innovative, interdisciplinary high quality research that relates to the understanding and exploitation of biological systems.

纳米技术产业对全球经济来说价值数十亿美元。然而，在纳米级（至少一维小于 100nm 的颗粒）上表现出的独特性质（例如表面反应性）并在这些行业中使用，可能会导致有毒性质，并且越来越多的实验证据表明这一点。从机械角度来看，产生活性氧（ROS）和诱导氧化应激的能力越来越被认为是解释与金属/金属氧化物纳米材料[NMs]颗粒相关的一些毒性效应的范例。在这个项目中，我们将把鱼类模型暴露于一些最广泛使用和商业上重要的 NM、银 (Ag) 和氧化铈 (CeO2)，并研究环境现实场景，以识别氧化应激对健康的潜在有害影响。通过使用用高度富集的稳定同位素标记的 NM、先进的成像方法（例如相干反斯托克拉曼散射）以及开发新型生物传感器斑马鱼模型，检测、量化和表征环境水平的复杂环境介质和生物体中的 NM 的能力将大大增强这项工作。检测氧化应激。在斑马鱼模型中，ROS 触发亲电反应元件 (EpRE) 报告基因（通常存在于参与保护细胞免受氧化损伤的基因的“启动子”（启动子）序列中），这将诱导产生可通过成像检测到的绿色荧光蛋白 (GFP)。开发这种新型生物传感器鱼的遗传方法已在埃克塞特成功应用于其他污染物的检测。该模型将能够实时识别氧化反应的靶组织。转录组学——测量数千个基因的反应——将用于识别选定 NM 暴露的反应（绿光）组织中的效应机制（分子途径）。转基因斑马鱼的研究结果将为英国河流原生鱼类（鲤鱼）在天然水中的 NM 暴露提供信息，以评估与 South West Water 合作的慢性健康状况。将对水中颗粒进行详细表征，以了解颗粒的命运和行为，并帮助了解它们被鱼类吸收的可用性。该项目将以跨学科团队的重要记录和出版物为基础，汇集广泛的基础设施和技术能力以及行业合作伙伴关系，以加深对具有商业重要性的纳米材料在现实环境条件下造成危害的潜力的了解。这项工作将支持纳米技术风险评估，以保护淡水水生环境和纳米技术产业的可持续发展。生成的所有数据将在同行评审文献、领先期刊上发表，并通过公共论坛和联络小组向利益相关者（例如公众、监管机构、行业）传播，合作伙伴与利益相关者拥有广泛的现有联系。拟议的项目与 NERC 的生物多样性、自然资源和环境的可持续利用、污染和人类健康的科学主题直接相关，也与 EC 欧洲水框架指令直接相关 - 加深我们对污染和废物的环境风险和危害的了解。该项目还支持 NERC 的使命目标，即促进与理解和利用生物系统相关的创新、跨学科高质量研究。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals.

最大程度地减少对遗产药物的鱼类的实验测试。

DOI：
10.1021/acs.est.2c07222
发表时间：
2023-01-31
期刊：
ENVIRONMENTAL SCIENCE & TECHNOLOGY
影响因子：
11.4
作者：
Coors, Anja;Brown, A. Ross;Maynard, Samuel K.;Perkins, Alison Nimrod;Owen, Stewart;Tyler, Charles R.
通讯作者：
Tyler, Charles R.

The influence of size and surface chemistry on bioavailability, tissue targets, and toxicity of gold nanoparticles in zebrafish (Danio Rerio) embryos: Implications for a potential environmental impact.

尺寸和表面化学对斑马鱼（Danio Rerio）胚胎中金纳米粒子的生物利用度、组织靶标和毒性的影响：潜在环境影响的影响。