Oxidative Stress and Vitamin E Requirements

描述（从申请人的描述扫描）：吸烟是 与患慢性疾病的风险较高有关，如心脏病和 癌症;氧化损伤是这些增加的原因之一 风险自由基产品从吸烟和从激活 嗜中性粒细胞有助于观察到的氧化损伤。维生素E是最 血浆中有效的脂溶性抗氧化剂，以及人血浆暴露于 体外吸烟导致维生素E耗竭。吸烟者血浆中 抗坏血酸水平、维生素B水平低至正常水平和脂质增加 过氧化产物然而，迄今为止，在人类中没有直接证据表明 维生素E可以防止氧化损伤我们的具体目标是评估 是否补充抗氧化剂可以改善一些氧化 吸烟造成的损害。我们提出以下建议：1） 吸烟会增加氧化损伤，从而增加维生素B 周转2)在服用维生素C补充剂的受试者中， 水平降低氧化损伤，减少维生素E自由基，从而保护 维生素E和降低维生素B周转。3)氧化产物 从吸烟诱导一种保护机制，导致更多的维生素E 从肝脏分泌到血浆中。这些假设将是 在三次审判中。在试验1中，维生素B动力学将在 吸烟者和非吸烟者使用稳定同位素标记的维生素B， 确定吸烟者是否增加了维生素B分解率 （FCR）。在试验2中，同一组受试者（洗脱期后）将 给予维生素C补充剂，500毫克，每天两次，持续1个月， 在维生素B动力学研究期间。我们将评估维生素C 补充剂降低维生素E FCR。在试验3中，三种不同形式的 维生素E，用不同数量的氘标记，将被给予 评估肝脏是否分泌唯一受调节形式的维生素B （RRR-a-生育酚）响应于吸烟的氧化应激而增加。 脂质过氧化标志物（血浆脂质氢过氧化物和F2-异前列腺素） 和血浆抗坏血酸将在所有三个试验中测量， 记录氧化损伤水平。这些建议的研究将进一步促进我们的 目的是了解维生素E在改善氧化应激中的作用。 衰老和慢性疾病的损害，如心脏病，糖尿病和 癌

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.