AN UPDATE ON ANTIOXIDANT THEORY: SPIN TRAPPING OF TRICHLOROMETHYL RADICALS IN VIVO
AN UPDATE ON ANTIOXIDANT THEORY: SPIN TRAPPING OF TRICHLOROMETHYL RADICALS IN VIVO
复制标题
抗氧化剂理论的更新：体内三氯甲基自由基的自旋捕获
DOI：
10.1111/j.1749-6632.1982.tb31229.x
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发表时间：
1982
影响因子：
5.2
通讯作者：
E. Lai
中科院分区：
文献类型：
--
作者：
P. McCay;M. King;J. Poyer;E. Lai
α-生育酚在生物系统中在分子水平上的精确功能尚未得到解决。虽然它的自由基清除和单线态氧猝灭特性是毋庸置疑的，但这些特性在多大程度上决定了它在动物中的需求。特别是在年轻的、快速生长的动物中，尚不清楚。许多结构上不相关的抗氧化剂似乎可以替代这种脂溶性维生素，但仍然有可能这些抗氧化剂只是保护非常微量的维生素E，以便有效量的维生素可以到达必需部位。维生素E活性的生物学表现可能涉及一种以上的功能。生育酚已被证明对各种临床问题有有益的作用，包括支气管肺发育不良，晶状体后纤维增生。与铁补充有关的溶血性贫血，以及某些肝中毒。根据动物模型的研究，维生素可能在前列腺素代谢中起重要作用。肾上腺皮质类固醇合成，红细胞生成，吞噬细胞功能，T细胞功能，自身免疫性疾病。和抑制肿瘤的促进。此外，这种维生素可用于预防与蒽环类抗生素阿霉素化疗相关的至少部分心脏损伤。在维生素E功能的研究中遇到的一些问题似乎既有概念方面的基础，也有所采用的实验条件的基础。后者的一个实例是与阿霉素同时肌内或腹膜内施用单剂量的α-生育酚乙酸酯，以测试维生素在改善由阿霉素引起的心脏病和死亡率方面的有效性。在这些条件下观察到非常少的有益效果，而在阿霉素治疗前24小时给予生育酚本身而不是酯提供了相当大的保护，以防止阿霉素死亡。18维生素的酯化形式在肌肉或腹膜中可能没有显著量的水解，并且，此外，当与阿霉素同时给予时，在损伤发生之前，它可能还没有结合到关键部位，而当游离维生素早于阿霉素给药时。观察到显著的保护作用。
The precise function or functions of a-tocopherol at the molecular level in biological systems have yet to be resolved. Although its free radical-scavenging and singlet oxygen-quenching properties are unquestioned, the extent to which these properties are responsible for its requirement in animals. particularly in young, rapidly growing animals, is not known. A number of structurally unrelated antioxidants appear to substitute for this fat-soluble vitamin, but it is still possible that such antioxidants are simply protecting very minute quantities of atocopherol so that effective amounts of the vitamin may reach the essential sites. It appears likely that more than one type of function is involved in the biological manifestations of vitamin E activity. Tocopherol has been shown to have beneficial effects in a variety of clinical problems including bronchopulmonary dysplasia, retrolental fibroplasia,'.* hemolytic anemia associated with iron s~pplementation,~ and certain toxic liver i n j ~ r i e s . ~ Based on investigations with animal models, the vitamin may play a significant role in prostaglandin me tabo l i~m,~-~ platelet f u n ~ t i o n , ~ . ~ adrenocortical steroid synthesis,1o," erythropoiesis," phagocyt~sis,'~ T-cell function,'* autoimmune disease." and inhibition of tumor promotion.'6 In addition, this vitamin may be useful in preventing at least part of the cardiac damage associated with chemotherapy with the anthracycline antibiotic ad r i amy~in . '~ , ' ~ Some of the problems encountered in the investigations of vitamin E function appear to have their basis in conceptual aspects as well as in the experimental conditions employed. An example of the latter is the administration of a single dose of a-tocopheryl acetate intramuscularly or intraperitoneally simultaneously with adriamycin to test the vitamin's effectiveness in ameliorating the cardiopathy and mortality caused by adriamycin ~ a r d i o t o ~ i ~ i t y . ' ~ ~ ' ~ Very little beneficial effect is observed under those conditions, whereas administration of tocopherol itself, rather than the ester, 24 hours prior to adriamycin treatment provides considerable protection against adriamycin mortality.18 The esterified form of the vitamin may not have been hydrolyzed in significant amounts in muscle or the peritoneum, and, in addition, when given at the same time as adriamycin, it may not have been incorporated into the critical sites before the damage was inflicted, whereas when the free vitamin was administered well ahead of the adriamycin. significant protection was observed.