A Study on the Action of Antioxidants and Development of Synergists

现在有越来越多的证据表明自由基介导的脂质、蛋白质、酶和核酸的氧化参与了各种病理事件、癌症和衰老。本研究旨在阐明各种断链抗氧化剂的作用速率和机理以及协同抑制氧化作用。水溶性抗氧化剂，如抗坏血酸（维生素C）、尿酸、半胱氨酸和谷胱甘肽，在水自由基攻击细胞膜之前清除它们，起到抗氧化剂的作用。然而，它们不能清除膜脂层内的亲脂自由基和低密度脂蛋白。生育酚（维生素E）在细胞膜内起亲脂抗氧化剂的作用。采用选择性自旋共振法测定了脂质过氧化自由基的吸氧、产物生成、化学发光和自由基的清除速率和清除机理。本文研究了磷脂脂质体膜的氧化作用及其抑制作用，旨在阐明抗氧化剂在磷脂脂质体膜中的作用。研究发现，生育酚通过清除膜外的水自由基和膜内的脂溶性自由基来抑制磷脂酰胆碱脂质体膜的氧化。有人认为，横向生育酚更快，但当它们深入到膜内部时，生育酚清除自由基的流出物更少。植基侧链对生育酚在细胞膜中的保留有深远的影响，但它使生育酚难以在细胞膜之间移动。另一方面，2,2,5,7,8-五甲基-6-铬醇可以在脂质体膜间自由穿透和转移。生育酚还能抑制自由基诱导的氧化溶血。发现红细胞膜内的生育酚通过清除携带链的自由基和破坏链的繁殖来抑制溶血最有效。研究了抗氧化剂与金属离子的相互作用。研究了生育酚与抗坏血酸、半胱氨酸和谷胱甘肽等还原剂协同抑制氧化的速率和机理。少

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