Manganese, Iron, Cadmium & Lead Transport from the Environment to Critical Organs

锰、铁、镉

• 批准号: 6968759
• 负责人: Joseph D Brain
• 金额: $ 9.5万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6968759
• 关键词: cadmium; central nervous system; environmental exposure; heavy metals; iron; laboratory rat; lead; manganese; mass spectrometry; mother /embryo /fetus nutrition; neurotoxicology; nutrition related tag; pharmacokinetics; polymerase chain reaction

Project #3 explores the transport of iron, manganese, cadmium and lead from environments experienced by children to the blood and critical organs like the brain, heart, liver, and kidney. We seek to better understand metal exposures of children and their mothers in settings like Tar Creek by (1) utilizing exposures during and after pregnancy, (2) using metal ions as well as complex environmental samples from Tar Creek, and (3) comparing different routes of entry from the environment into the body. Project 3 will also explore the role of toxic metals and iron status as they interact to influence metal absorption. In animal models, we will simultaneously study both the molecular mechanisms of metal transport as well as the corresponding pharmacokinetics of metals from the nose, lung and gut to the blood, central nervous system, and other organs. These data will be correlated with outcomes in both animal (Project 4) and human studies (Project 1). When data from Project 3 are combined with exposure assessment in Project 2, we will be able to better identify which routes of exposure result in the most significant body burdens of toxic metals. From this knowledge, we should be able to craft optimal strategies in Tar Creek to reduce the dose of toxic metals to mothers and children and thus better respond to the environmental concerns of the citizens in Tar Creek, Oklahoma.

项目3探讨了铁、锰、镉和铅从儿童所经历的环境到血液和关键器官(如大脑、心脏、肝脏和肾脏)的运输。我们试图通过(1)利用怀孕期间和怀孕后的暴露，(2)使用金属离子以及来自焦油溪的复杂环境样本，以及(3)比较不同的途径，来更好地了解儿童及其母亲在焦油溪等环境中的金属暴露。 从环境进入身体。项目3还将探讨有毒金属和铁的状态在它们相互作用影响金属吸收时的作用。在动物模型中，我们将同时研究金属从鼻、肺和肠道到血液、中枢神经系统和其他器官的转运的分子机制以及相应的药代动力学。这些数据将与两种动物的结果相关联 (项目4)和人体研究(项目1)。当项目3中的数据与项目2中的暴露评估相结合时，我们将能够更好地识别哪些暴露途径会导致最显著的有毒金属身体负担。根据这些知识，我们应该能够在焦油溪制定最佳战略，以减少有毒金属对母亲和儿童的剂量，从而更好地回应俄克拉荷马州焦油溪市民对环境的关切。