THERAPEUTIC ROLE OF NATURAL ANTIOXIDANTS IN LEAD POISONI

天然抗氧化剂对铅中毒的治疗作用

• 批准号: 2666546
• 负责人: NURAN ERCAL
• 金额: $ 10.88万
• 依托单位: MISSOURI UNIVERSITY OF SCIENCE & TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2666546
• 关键词: acetylcysteine; antioxidants; ascorbate; chelating agents; chelation therapy; diet therapy; dietary supplements; drug screening /evaluation; environmental toxicology; laboratory rat; lead poisoning; nonhuman therapy evaluation; nutrition related tag; oxidative stress; pharmacokinetics; short chain fatty acid; taurine; tocopherols

DESCRIPTION: (Adapted from the Investigator's Abstract) Despite the fact that 3 million children are affected by lead poisoning, efforts to treat these children and to eliminate lead from the environment have been inadequate. At present, the only approved clinical intervention method is chelation with calcium disodium ethylenediaminetetraacetic acid (CaNaEDTA), D-penicillamine, and British Anti-Lewisite. CaNaEDTA in particular, is widely used despite its high cost ($30,000 per child) and severe side effects. The most undesirable effects observed during CaNaEDTA treatment were the increased urinary excretion of zinc and iron, and the redistribution of lead from its innocuous bone site to crucial soft tissues such as the brain. For these reasons, most physicians prefer not to treat children with lead levels of less than 45 ug/dL. In addition to other toxicities, lead has been shown to induce oxidative stress both in vivo and in vitro. Our previous studies demonstrated that treatment with N-acetylcysteine (NAC) seemed to improve oxidative stress parameters and it also showed some chelating action in lead-exposed animals. These data suggest that antioxidants may play an important role as therapeutic agents in lead poisoning. We speculate that an effective long-term therapy for lead poisoning must encompass both a chelating agent and antioxidant administration. The proposed work will explore the use of the natural antioxidants alpha-lipoic acid, taurine, alpha-tocopherol (vitamin E), and ascorbic acid (vitamin C) in treatment of lead poisoning. At least three important benefits will be derived from the proposed study: 1. The role of oxidative stress in lead toxicity will be clarified; 2. The benefits of various antioxidants in subclinical lead intoxication (blood lead less than 45 ug/dL) will be examined; 3. The adjunctive use of antioxidants with a new oral chelator succimer will be explored in clinical lead intoxication (blood lead greater than 45 ug/dL). Eventually we hope to provide evidence that the use of antioxidants will offer safe and effective treatment for a segment of the human population (children with moderate blood-lead levels) presently left untreated.

描述：（根据调查员的摘要改编），尽管事实 300万儿童受到铅中毒的影响，努力治疗 这些孩子并消除了环境的领导 不足。 目前，唯一认可的临床干预方法是 螯合钙二钠乙二胺乙酸（CANAEDTA）， d-苯胺胺和英国抗Lewisite。 特别是Canaedta，是 尽管成本很高（每个孩子$ 30,000）和严重的一面，但使用了广泛使用 效果。 在Canaedta处理期间观察到的最不受欢迎的效果 是锌和铁的尿排泄增加吗？ 将铅从其无害的骨位点重新分布到关键的软组织 例如大脑。 由于这些原因，大多数医生都不喜欢治疗 铅含量小于45 ug/dl的儿童。 除其他 毒性，已显示铅在体内诱导氧化应激 体外。 我们以前的研究表明，与 N-乙酰半胱氨酸（NAC）似乎改善了氧化应激参数，IT 还显示了铅暴露动物的螯合作用。 这些数据 表明抗氧化剂可以作为治疗剂发挥重要作用 在铅中毒中。 我们推测有效的长期治疗 铅中毒必须涵盖螯合剂和抗氧化剂 行政。 拟议的工作将探索自然的使用 抗氧化剂α-硫酸，牛磺酸，α-生育酚（维生素E）和 抗坏血酸（维生素C）治疗铅中毒。 至少三个 重要的好处将来自拟议的研究：1。 铅毒性中的氧化应激将被阐明； 2。 亚临床铅中毒中的各种抗氧化剂（血液铅少于 将检查45 ug/dl）； 3。抗氧化剂的辅助用途 新的口服螯合剂婚姻将在临床铅中毒中探索 （血液铅大于45 ug/dl）。 最终我们希望提供证据 使用抗氧化剂将为A提供安全有效的治疗 人口的细分市场（中等血统水平的儿童） 目前未经处理。