HEPATOTOXICITY OF ATRAZINE AND ITS DEGRADATION PRODUCTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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广泛的除草剂之一。我们的研究主要集中在阿特拉津及其降解产物在水环境中的肝毒性研究。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而产生肝毒性。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(去乙基阿特拉津、去异丙基阿特拉津、羟基阿特拉津、去异丙基羟基阿特拉津和去烷基阿特拉津)对NADPH诱导的大鼠肝微粒体脂质过氧化的影响。方法：采用体外孵育试验。孵育结束后，用四甲基偶氮唑蓝比色法(TBAS)和高效液相-质谱仪/质谱仪(HPLC-MS/MS)检测细胞中的醛类化合物和4-羟基壬烯醛，以评估细胞的氧化应激状态。结果：羟基阿特拉津可显著增强脂质过氧化作用，而其他5种化合物均无明显作用。与阿特拉津相比，羟基阿特拉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。说明羟基阿特拉津特殊的电荷分布在增强脂质过氧化中起着重要作用。此外，我们开发了一种有效的基于纳米颗粒的固相萃取方法来从水样中提取/浓缩这些农用化学品，并用于随后的液相色谱-串联质谱联用定量分析。据我们所知，这是此类协议中的第一个。相信该议定书将在环境健康、修复和毒理学等研究领域得到广泛应用。

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.