THERAPEUTIC ROLE OF NATURAL ANTIOXIDANTS IN LEAD POISONI

描述：(改编自《调查者摘要》) 300万儿童受铅中毒影响，努力治疗 为了消除环境中的铅，这些儿童已经 不够充分。目前，唯一被批准的临床干预方法是 与乙二胺四乙酸钙二钠(CaNaEDTA)络合， D-青霉胺和英国反路易斯特。尤其是CaNaEDTA，是 被广泛使用，尽管它的成本很高(每个孩子30,000美元)和严重的副作用 效果。在CaNaEDTA治疗期间观察到的最不良影响 是尿锌和铁的排泄增加，以及 铅从无害的骨骼部位到关键软组织的重新分布 比如大脑。出于这些原因，大多数医生不愿治疗 铅水平低于45ug/dL的儿童。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 在试管中。我们之前的研究表明，使用 N-乙酰半胱氨酸(NAC)似乎可以改善氧化应激参数，而且它 在铅暴露的动物中也显示出一些螯合作用。这些数据 提示抗氧化剂可能作为治疗剂发挥重要作用 死于铅中毒。我们推测一种有效的长期治疗方法 铅中毒必须同时含有螯合剂和抗氧化剂。 行政管理。拟议的工作将探索使用天然的 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)在铅中毒治疗中的应用至少三个 拟议的研究将带来重要的好处：1. 铅毒性中的氧化应激将被阐明；2. 各种抗氧化剂在亚临床铅中毒(血铅< 45ug/dL)将被检查；3.抗氧化剂与 新的口服螯合剂琥珀酸将用于临床铅中毒 (血铅大于45ug/dL)。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 人群中的一部分(血铅水平中等的儿童) 目前没有得到治疗。

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.