INHIBITION OF PARAQUAT OXYGEN-MEDIATED TOXICITY

抑制百草枯氧介导的毒性

• 批准号: 3081185
• 负责人: MICHAEL J KELNER
• 金额: $ 6.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081185
• 关键词: antioxidants; biotransformation; detoxification; environmental toxicology; histopathology; paraquat; pesticide biological effect; superoxides; tissue /cell culture; toxin metabolism

It is proposed that the effects of methylene blue and thionin on paraquat toxicity be investigated using rats as the experimental model. Paraquat produces its toxic effects by oxygen-radical production, NADPH depletion, and mixed disulfide production. Methylene blue and thionin are known to stimulate NADPH production and preliminary experiments show they will replace oxygen as electron carriers and also react with oxygen radicals. By replacing oxygen as the electron carrier, methylene blue and thionin should prevent the formation of oxygen or paraquat radicals. Previous attempts to reduce paraquat toxicity used agents that worked by removing the radicals after their formation. Information derived from this project would also be used to investigate other environmental toxins (lead, aromatic-nitrate solvents) that may produce oxygen radicals at a slower rate. The principal investigator is interested in a career in environmental toxicology with research emphasis on biochemical changes in anti-oxidant enzyme systems from environmental chemicals. The above project will enable the investigator to study a well defined oxygen-radical producing system and interaction with anti-oxidant enzyme systems. By introducing a change in the system (methylene blue or thionin) an original contribution to scientific knowledge may also be made. The award would enable the investigator to devote full time to environmental toxicology (80% research, 20% clinical or teaching) by removing all other duties or responsibilities. The University of California, San Diego has excellent research and clinical facilities for studying environmental toxicology. There is a clinical occupational health group at the University of California, San Diego-Medical Center and an environmental toxicology program at the San Diego Zoo. In addition, the University's close proximity to Mexico provides unique exposure to environmental problems not found in the United States. The principal investigator will be able to participate in both of the above programs. It is anticipated that the principal investigator, following completion of the program, will join the Department of Pathology at the University of California, San Diego as an Assistant Professor with research, teaching, and clinical responsibilities in environmental toxicology.

提出亚甲基蓝和硫堇对百草枯的影响 以大鼠为实验模型研究其毒性。 百草枯 通过氧自由基的产生、NADPH的消耗， 和混合二硫化物的生产。 已知亚甲蓝和硫堇 刺激NADPH产生，初步实验表明， 取代氧作为电子载体，并且还与氧自由基反应。 通过取代氧作为电子载体，亚甲蓝和硫堇 应防止氧或百草枯自由基的形成。 先前 为了减少百草枯的毒性， 形成后的激进分子。 从本项目中获得的信息 也可用于研究其他环境毒素（铅， 芳香族硝酸盐溶剂），其可以以较慢的速率产生氧自由基。 率 首席研究员对环境领域的职业感兴趣 毒理学，重点研究抗氧化剂的生化变化 酶系统的环境化学品。 上述项目将使 研究人员研究了一个定义明确的氧自由基产生系统 以及与抗氧化酶系统的相互作用。 通过引入改变 在系统中（亚甲蓝或硫堇）， 科学知识也是可以创造的。 该裁决将使 研究人员将全部时间用于环境毒理学（80%的研究， 20%临床或教学），取消所有其他职责或责任。 加州大学圣地亚哥分校拥有优秀的研究和临床 研究环境毒理学的设施。 涉及一项临床 位于旧金山的加州大学的职业健康小组 圣地亚哥医疗中心和圣地亚哥环境毒理学项目 迭戈动物园。 此外，该大学靠近墨西哥， 提供了独特的暴露在环境问题没有发现在美国 States. 主要研究者将能够参加以下两项研究： 上述方案。 预计首席研究员， 完成该计划后，将加入病理学系 在加州大学圣地亚哥分校担任助理教授， 研究，教学和临床责任，在环境 毒理学