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：（改编自研究者摘要）尽管事实上 有300万儿童受到铅中毒的影响， 这些儿童和消除环境中的铅， 不足 目前，唯一批准的临床干预方法是 与乙二胺四乙酸二钠钙（CaNaEDTA）螯合， D-青霉胺和英国抗路易氏剂 特别是CaNaEDTA， 尽管成本高（每个孩子30，000美元）且严重，但仍被广泛使用 方面的影响. 在CaNaEDTA治疗期间观察到的最不希望的作用 尿锌和铁排泄增加， 铅从无害骨部位向重要软组织的再分布 比如大脑。 由于这些原因，大多数医生不愿意治疗 儿童铅含量低于45微克/分升。 除了其他 毒性，铅已被证明在体内和体内都能诱导氧化应激， 体外 我们以前的研究表明， N-乙酰半胱氨酸（NAC）似乎可以改善氧化应激参数， 在铅暴露的动物中也显示出一定的螯合作用。 这些数据 提示抗氧化剂可能作为治疗剂发挥重要作用 铅中毒 我们推测，一种有效的长期治疗， 铅中毒必须包括螯合剂和抗氧化剂 局 拟议中的工作将探讨利用自然 抗氧化剂α-硫辛酸、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 建议的研究将带来以下重要益处： 的作用 铅毒性中的氧化应激将被阐明; 2. 的好处 亚临床铅中毒（血铅低于 45 ug/dL）进行检查; 3. 抗氧化剂的连续使用 一种新的口服螯合剂琥珀酰亚胺将在临床铅中毒中探索 （血铅大于45微克/分升）。 最终我们希望能提供证据 抗氧化剂的使用将提供安全有效的治疗， 部分人群（血铅水平中等的儿童） 目前未得到治疗。