HEPATOTOXICITY OF ATRAZINE AND ITS DEGRADATION PRODUCTS

阿特拉津及其降解产物的肝毒性

• 批准号: 7715350
• 负责人: YIMING LIU
• 金额: $ 13.54万
• 依托单位: JACKSON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715350
• 关键词: 4 hydroxynonenal; Area; Atrazine; Biological Assay; Charge; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Coupled; Environment; Environmental Health; Exhibits; Funding; Grant; Hepatotoxicity; Herbicides; In Vitro; Institution; Knowledge; Lipid Peroxidation; Liquid Chromatography; Liver Microsomes; Methods; NADP; Oxidative Stress; Phase; Play; Procedures; Protocols documentation; Rattus; Research; Research Personnel; Resources; Role; Solid; Source; Structure-Activity Relationship; Testing; Toxicology; United States National Institutes of Health; base; deethylatrazine; nanoparticle; remediation; tandem mass spectrometry; water sampling

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatotoxicity of Atrazine and Its Degradation Products Atrazine is one of the herbicides most heavily used in the world. Our research has been focused on studies of hepatotoxicity of atrazine and its degradation products in aquatic environments. Our hypothesis was that atrazine and its degradation products exert hepatotoxicity via a mechanism of enhancing lipid peroxidation. In the funding period from 6/07 to 5/08, we studied atrazine and its five degradation products (i.e. deethylatrazine, deisopropylatrazine, hydroxyatrazine, deisopropylhydroxyatrazine, and didealkylatrazine) to examine their effects on NADPH induced lipid peroxidation in rat liver microsome. Methods: In vitro incubation tests were performed. After incubation, TBAS assay for aldehydic compounds and HPLC-MS/MS assay for 4-hydroxynonenal were carried out to assess the oxidative stress status. Results: The study revealed that hydroxyatrazine enhanced significantly the lipid peroxidation while the other five compounds tested did not exhibit observable effects. Significant damage was caused by hydroxyatrazine as evaluated against atrazine. Computational modeling study was performed to identify potential structure-activity relationships. It seemed that the particular charge distribution in hydroxyatrazine played an important role in enhancing lipid peroxidation. In addition, we developed an effective nanoparticle-based solid phase extraction procedure to extract/enrich these agrichemicals from water samples for subsequent quantitative assay by liquid chromatography coupled to tandem mass spectrometry. This protocol was the first of its kind to the best of our knowledge. It is believed that the protocol will find wide applications in research areas such as environmental health, remediation, and toxicology.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 阿特拉津及其降解产物的肝毒性 阿特拉津是世界上使用最多的除草剂之一。本课题主要研究阿特拉津及其降解产物在水环境中的肝毒性。我们的假设是，阿特拉津及其降解产物通过增强脂质过氧化作用的机制产生肝毒性。在2007年6月至2008年5月的资助期内，我们研究了阿特拉津及其五种降解产物（即脱乙基阿特拉津、脱异丙基阿特拉津、羟基阿特拉津、脱异丙基羟基阿特拉津和二脱烷基阿特拉津），以检查它们对NADPH诱导的大鼠肝微粒体脂质过氧化的影响。方法：体外培养试验。孵育后，进行TBAS测定法和HPLC-MS/MS测定法，以评估氧化应激状态。结果如下：研究表明，羟基阿特拉津显着增强脂质过氧化作用，而其他五种化合物测试没有表现出可观察到的效果。与莠去津相比，羟基莠去津造成了显著的损害。进行了计算建模研究，以确定潜在的结构-活性关系。羟基阿特拉津的特殊电荷分布在增强脂质过氧化反应中起重要作用。此外，我们开发了一种有效的基于纳米颗粒的固相萃取程序，从水样中提取/富集这些农药，用于随后的液相色谱-串联质谱定量分析。据我们所知，这是第一个此类协议。相信该协议将在环境健康、修复和毒理学等研究领域得到广泛应用。