Exner M, Hermann M, Hofbauer R, Kapiotis S, Quehenberger P, Speiser W, Held I, Gmeiner B M
Department of Laboratory Medicine, University of Vienna, Austria.
Free Radic Res. 2001 Jan;34(1):101-12. doi: 10.1080/10715760100300101.
Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.
高血糖一直被认为是糖尿病氧化应激的原因。在这方面，葡萄糖自氧化和晚期糖基化终产物（AGE）可能在糖尿病并发症（如动脉粥样硬化）的病因中起因果作用。现在越来越多的证据表明，低密度脂蛋白（LDL）的氧化修饰在动脉粥样硬化形成中起潜在作用。已证明葡萄糖衍生的氧化剂可使LDL过氧化。在本研究中，已评估了染料木黄酮（一种具有黄酮类化学结构的大豆衍生化合物，4'，5，7-三羟基异黄酮）作为抗氧化剂抵抗葡萄糖自氧化自由基产物对LDL致动脉粥样硬化修饰的能力。大豆中的另一种植物雌激素黄豆苷元（4'，7-二羟基异黄酮）也进行了平行测试。与黄豆苷元相比，染料木黄酮有效地防止了葡萄糖介导的LDL氧化，这通过硫代巴比妥酸反应性物质形成（TBARS）、电泳迁移率改变、脂质氢过氧化物以及脂蛋白色氨酸残基的荧光猝灭来衡量。此外，当在葡萄糖对LDL进行氧化修饰期间存在染料木黄酮时，葡萄糖氧化的LDL增加人内皮细胞（HUVEC）组织因子（TF）合成的潜力被完全抑制。两种植物雌激素均未影响通过糖化LDL的体外形成所测量的非酶蛋白糖基化反应。由于在体内可能出现的葡萄糖/染料木黄酮摩尔比下发现了染料木黄酮对LDL动脉粥样硬化修饰的保护作用，我们的研究结果支持了大豆饮食在预防慢性血管疾病和早期动脉粥样硬化事件方面的有益作用。
