TRANSITION-METAL MEDIATED FREE RADICAL FORMATION IN VITRO AND IN VIVO

过渡金属介导的体外和体内自由基形成

• 批准号: 3777537
• 负责人: R P MASON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3777537
• 关键词: carcinogenesis; chromium; electron spin resonance spectroscopy; free radical oxygen; free radicals; hydroxyl radical; iron; laboratory rat; metal poisoning; occupational hazard; superoxides

Increasing evidence indicates that probably most acute and chronic metal poisoning involve free radical reactions in tissue injury. Since the concentration of radicals occurring in body tissues is generally near the sensitivity limit of ESR spectroscopy, the spin trapping technique is used. The manipulation of an animal model also provides evidence that the toxicity is indeed free radical mediated. By successfully applying this approach, ESR evidence has been obtained for free radical formation generated by iron may occur in vivo not only after acute but also after chronic iron intake. Chromium (VI) compounds pose a serious occupational health hazard in terms of both their potential respiratory tract carcinogenicity and their toxic effect on other organs. By applying ESR and a spin trapping technique, the existence of a radical adduct has also been shown in bile of rats after acute Cr(VI) poisoning. Additional measurements are carried out to provide more data about the exact mechanism by which the detected free radicals from Cr(VI) intoxication are formed. We were not able to show free radical formation in bile or in different tissues (brain, liver, kidneys) after poisoning of rats with lead or with aminolevulinic acid. We also found lack of toxic synergistic effects of Pb and Fe or Al and Fe after these acute metal-metal poisonings.

越来越多的证据表明，可能大多数急性和慢性金属 中毒涉及组织损伤中的自由基反应。 自从 身体组织中发生的自由基浓度通常接近 为了达到ESR光谱的灵敏度极限，采用了自旋捕获技术。 动物模型的操作也提供了证据表明 毒性确实是自由基介导的。 通过成功应用此 方法，已获得自由基形成的 ESR 证据 铁产生的体内不仅可能发生在急性发作后，而且发生在急性发作后。 长期铁摄入量。 六价铬化合物对职业健康造成严重危害 就其潜在的呼吸道致癌性及其 对其他器官的毒性作用。 通过应用 ESR 和自旋捕获 技术，胆汁中也显示了自由基加合物的存在 急性 Cr(VI) 中毒后的大鼠。 进行额外的测量 提供有关确切机制的更多数据 检测到因 Cr(VI) 中毒而形成的自由基。 我们不是 能够显示胆汁或不同组织（脑、 铅或氨基乙酰丙酸中毒大鼠后（肝、肾） 酸。 我们还发现 Pb 和 Fe 或 Al 缺乏毒性协同作用 和这些急性金属中毒后的铁。