A Study on the Action of Antioxidants and Development of Synergists

抗氧化剂的作用研究及增效剂的开发

• 批准号: 62470078
• 负责人: NIKI Etsuo
• 金额: $ 4.42万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62470078/
• 关键词: Antioxidants; Autoxidation; Free Radical; Vitamin E; Lipid peroxidation; ビタミンC; 芳香族アミン

There is now an increasing number of evidence which suggests the involvement of free radical mediated oxidations of lipids, proteins, enzymes, and nucleic acids in a variety of pathological events, cancer and aging. This study was carried out aiming at elucidating the rate and mechanism of the action of various chain-breaking antioxidants and also the synergistic inhibition of oxidation.The water-soluble antioxidants such as ascorbic acid (vitamin C), uric acid, cysteine, and glutathione acted as antioxidant by scavenging aqueous radicals before they attack the membranes.However, they can not scavenge lipophilic radicals within the lipid layer of membranes and low density lipoprotein. Tocopherols (vitamin E) acted as lipophilic antioxidant within the membranes.The rate and mechanism of scavenging of lipid peroxyl radicals were fint studied in homogeneous solution by measuring oxygen uptake, products formation, chemiluminescence, and free radicals with election spin resonance. The oxida … More tion of phospholipid liposomal membranes and its inhibition were studied aiming specifically at elucidating the action of antioxidants in the membranes. It was found that tocopherols suppress the oxidation of phosphatidylcholine liposomal membranes by scavenging both aqueous radicals attacking from outside of the membranes and lipophific radicals within the membranes. It was suggested that laterally tocopherols more fairly rapidly but that it gets less effluent for tocopherols to scavenge radicals as they go deeper into the interior of the membrane. The phytyl side chain had a profound effect in the retainment of tocopherols in the membranes but it makes tocopherols difficult to move between the membranes. On the other hand, 2,2,5,7,8-pentamethyl-6-chromanol could penetrate and transfer between the liposomal membranes freely. Tocophemls also suppressed the oxidative hemolysis induced by free radicals. It was found that tocopherol within the erythrocyte membranes was the most effective in suppressing hemolysis by scavenging chain-carrying radicals and breaking the chain propagation. The interaction between antioxidants and metal ion was also studied. The rate and mechanism of synergistic inhibition of oxidation by tocopherol and reducing agent such as ascorbic acid, cysteine and glutathione have been also studied. Less

现在有越来越多的证据表明，自由基介导的脂类、蛋白质、酶和核酸的氧化参与了各种病理事件，如癌症和衰老。本研究旨在阐明各种断链抗氧化剂的作用速度、作用机理以及协同抑制氧化作用。抗坏血酸(维生素C)、尿酸、半胱氨酸和谷胱甘肽等水溶性抗氧化剂作为抗氧化剂，在攻击膜之前清除水自由基，但不能清除膜脂层和低密度脂蛋白中的亲脂自由基。生育酚(维生素E)作为膜内的亲脂性抗氧化剂，通过电子自旋共振测量氧摄取量、产物形成、化学发光和自由基，研究了均相溶液中脂质过氧化自由基的清除速率和机理。The Oxa…进一步研究了磷脂脂膜及其抑制作用，旨在阐明抗氧化剂在膜中的作用。研究发现，生育酚通过清除膜外的水自由基和膜内的亲脂自由基来抑制磷脂酰胆碱脂质体的氧化。有人认为，横向生育酚相当快，但当生育酚深入膜内部时，清除自由基的流出物较少。植基侧链对生育酚在膜中的保留有深远的影响，但它使生育酚难以在膜之间移动。另一方面，2，2，5，7，8-五甲基-6-色满酚可以自由穿透并在脂质体之间传递。Tocophemls还能抑制自由基诱导的氧化溶血作用。研究发现，红细胞膜中的生育酚通过清除携带链的自由基和破坏链传播而最有效地抑制溶血。研究了抗氧剂与金属离子的相互作用。研究了生育酚与抗坏血酸、半胱氨酸、谷胱甘肽等还原剂协同抑制氧化的速率和机理。较少

项目成果

E.Niki: "Cellular Antioxidant Defense Mechanisms.Vol.II" CRC Press,Boca Raton,Florida, 505 (1988)

E.Niki：“细胞抗氧化防御机制.Vol.II”CRC Press，博卡拉顿，佛罗里达州，505 (1988)

M. Takahashi, J. Tsuchiya, and E. Niki: "Oxidation of lipids. XVI. Inhibition of autoxidation of methyl linoleate by diarylamines" Bull. Chem. Soc. Jpn., 62, 1880-1884 (1989).

M. Takahashi、J. Tsuchiya 和 E. Niki：“脂质的氧化。XVI. 二芳基胺对亚油酸甲酯自动氧化的抑制”Bull。

M.Takahashi: "Oxidation of lipids.XVII.Inhibition of autoxidation of methyl linoleate by diarylamines." Bull.Chem.Soc. Jpn.62. 1880-1884 (1989)

M.Takahashi：“脂质的氧化。XVII.二芳基胺对亚油酸甲酯的自氧化的抑制。”

O.Hayaishi,E.Niki,et al.,eds.: "Medical,Biochemical and Chemical Aspects of Free Radicals" Elsevier,Amsterdam, 1989

O.Hayaishi,E.Niki,et al.,eds.：“自由基的医学、生化和化学方面”Elsevier，阿姆斯特丹，1989

M.Matsuo: "Radical-scavenging reactions of vitamin E and its model compound,2,2,5,7,8-pentamethylch man-6-o1,in a tert-butylperoxyl redical-generating system." J.Am.Chem.Soc.111. 7179-7185 (1989)

M.Matsuo：“维生素 E 及其模型化合物 2,2,5,7,8-pentamethylch man-6-o1 在叔丁基过氧化自由基生成系统中的自由基清除反应。”