THERAPEUTIC ROLE OF ANTIOXIDANTS IN LEAD POISONING

抗氧化剂在铅中毒中的治疗作用

• 批准号: 6224882
• 负责人: NURAN ERCAL
• 金额: $ 11.1万
• 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 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6224882
• 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

Despite the fact that 3 million children are affected by lead poisoning each year in the United States, efforts to treat these children and to eliminate lead from the environment have been inadequate. Although chelating agents are currently available for the treatment of lead poisoning, they have been shown to have severe side effects. Lead poisoning is stated as a multifaceted problem since disruption of a variety of biochemical processes is responsible for toxicity rather than a single mechanism. Even though oxidative stress appears to play a major role, the molecular mechanisms of lead toxicity are not completely known. Our previous studies demonstrated that treatment with thiols (N-acetylcystein, alpha-lipoic acid and captopril) significantly reversed lead-induced alterations in oxidative stress parameters, in both in vivo and in vitro models. However, none of these antioxidants showed any significant chelating action for lead. In order to improve the chelating abilities of thiol antioxidants in the treatment of lead poisoning, we propose to use their unnatural enantiomers because their natural, biologically-active enantiomers are quickly metabolized, whereas their unnatural ones are not. This is due to the fact that enzymes in living systems are usually stereoselective. Therefore, this continuation of our NIH (1R15ES 09497-01) proposal will explore chelating actions of the unnatural thiol enantiomers, particularly D-NAC and D-Cysteine in lead poisoning. This research will produce more effective and safe therapeutic agents for chelation by exploiting biological dependence on stereochemistry. In addition, the proposal may offer insights into our understanding of the mechanisms of enantiomeric selectivity of thiols in general.

尽管美国每年有300万儿童受到铅中毒的影响，但治疗这些儿童和从环境中消除铅的努力还不够。虽然螯合剂目前可用于治疗铅中毒，但它们已被证明具有严重的副作用。

项目成果

N-acetyl-L-cysteine protects against delta-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation.

N-乙酰基-L-半胱氨酸可防止 δ-氨基乙酰丙酸诱导的 8-羟基脱氧鸟苷形成。

• DOI: 10.1016/s0378-4274(99)00014-4
• 发表时间: 1999
• 期刊: Toxicology letters
• 影响因子: 3.5
• 作者: Yusof,M;Yildiz,D;Ercal,N
• 通讯作者: Ercal,N