Oxidative Stress and Vitamin E Requirements

描述(从申请者的描述中扫描)：吸烟是 与慢性疾病的高风险有关，如心脏病和 癌症；氧化损伤是导致这些增加的原因之一 风险。吸烟和活化产生的自由基产物 中性粒细胞导致了观察到的氧化损伤。维生素E是最多的 血浆中有效的脂溶抗氧化剂，以及人体血浆暴露于 体外吸烟会导致维生素E的耗尽吸烟者的血浆含量很低 抗坏血酸水平，低至正常的维生素B水平和增加的血脂 过氧化产物。然而，到目前为止，在人类身上还没有直接的证据 维生素E可以防止氧化损伤。我们的具体目标是评估 补充抗氧化剂是否可以改善体内某些氧化反应 吸烟造成的损害。我们建议如下：1) 吸烟会增加氧化损伤，从而增加维生素B 营业额。2)在服用维生素C补充剂的受试者中，维生素C增加 减少氧化损伤，减少维生素E自由基，从而保护 维生素E和减少维生素B的周转。3)生成的氧化产物 吸烟会产生一种保护机制，从而产生更多的维生素E 从肝脏分泌到血浆中。这些假设将是 在三个试验中得到了解决。在试验1中，维生素B动力学将在 吸烟者和不吸烟者使用稳定同位素标记的维生素B来 确定吸烟者是否增加了维生素B的部分分解代谢率 (FCR)。在试验2中，同一组受试者(经过一段时间后)将 服用维生素C补充剂，每日两次，每次500毫克，前后各1个月 在维生素B动力学研究期间。我们将评估维生素C是否 补充剂可以降低维生素E的FCR。在试验3中，三种不同形式的 维生素E，标有不同数量的氘，将被注射到 评估肝脏分泌的唯一受调控形式的维生素B (RRR-a-生育酚)是对吸烟的氧化应激反应的增加。 脂质过氧化的标记物(血浆过氧化脂质和F2-异前列腺素) 血浆抗坏血酸将在所有三个试验中进行测量，以 记录氧化损伤的级别。这些拟议的研究将进一步推动我们的 了解维生素E在改善氧化损伤中的作用 老化和慢性疾病造成的损害，如心脏病、糖尿病和 癌症。

DESCRIPTION (Scanned from the applicant's description): Cigarette smoking is associated with a higher risk for chronic diseases, such as heart disease and cancer; oxidative damage is one of the contributing causes of these increased risks. Free radical products from cigarette smoking and from activated neutrophils contribute to the observed oxidative damage. Vitamin E is the most potent, lipid soluble antioxidant in plasma, and exposure of human plasma to smoke in vitro results in depletion of vitamin E. Smokers' plasma contains low ascorbic acid levels, low to normal vitamin B levels and increased lipid peroxidation products. However, to date, there is no direct evidence in humans that vitamin E prevents oxidative damage. Our specific goal is to evaluate whether antioxidant supplementation might ameliorate some of the oxidative damage that results from cigarette smoking. We propose the following: 1) Cigarette smoking increases oxidative damage and thus, increases vitamin B turnover. 2) In subjects taking vitamin C supplements, increased vitamin C levels decrease oxidative damage and reduce vitamin E radicals, thus protecting vitamin E and decreasing vitamin B turnover. 3) Oxidation products resulting from cigarette smoking induce a protective mechanism that causes more vitamin E to be secreted from the liver into the plasma. These hypotheses will be addressed in three trials. In Trial 1, vitamin B kinetics will be measured in smokers and non-smokers using vitamin B labeled with stable isotopes to determine whether smokers have increased vitamin B fractional catabolic rates (FCRs). In Trial 2, the same group of subjects (after a washout period) will be given vitamin C supplements, 500 mg twice a day for 1 month prior to and then during the vitamin B kinetics study. We will assess whether vitamin C supplements decrease vitamin E FCRs. In Trial 3, three different forms of vitamin E, labeled with differing amounts of deuterium, will be administered to assess whether hepatic secretion of the only regulated form of vitamin B (RRR-a-tocopherol) is increased in response to the oxidative stress of smoking. Markers of lipid peroxidation (plasma lipid hydroperoxides and F2-isoprostanes) and plasma ascorbic acid will be measured throughout all three trials to document levels of oxidative damage. These proposed studies will further our goal of understanding the role of vitamin E in the amelioration of oxidative damage in aging and in chronic diseases, such as heart disease, diabetes and cancer.