Jovanovic S V, Clements D, MacLeod K
International Center for Metabolic Testing, Ottawa, Ontario, Canada.
Free Radic Biol Med. 1998 Dec;25(9):1044-8. doi: 10.1016/s0891-5849(98)00137-3.
There is convincing epidemiological and in vitro evidence of chronic oxidative stress in individuals with Down syndrome (DS). These individuals develop Alzheimer like changes in the brain in their 30s and 40s. The incidence of autoimmune diseases and cataracts is significantly increased, and the overall ageing process is accelerated. In vitro studies show that impaired viability of DS neurons may be amended by simple chemical antioxidants, such as vitamin E, BHT and propyl gallate, clearly indicative of oxyl radical involvement. However, because of the lack of in vivo experiments, the role of oxidative stress in DS remains controversial. We report here on the results of the chemical analyses of urine samples of 166 individuals, where DS subjects were matched by their siblings. The levels of 8-hydroxy-2'-deoxyguanosine (2.35 +/- 1.69 in DS vs. 1.35 +/- 1.04 in controls, P = 0.00011), a biomarker of oxidative damage to DNA, and malondialdehyde (0.255 +/- 0.158 in DS vs. 0.204 +/- 0.128 in controls, P = 0.033), a biomarker of lipid peroxidation, are significantly elevated in individuals with DS. Dietary influences failed to show any significant correlation with the oxidative stress biomarkers. These results provide direct evidence for increased oxidative stress in individuals with DS.
有令人信服的流行病学和体外证据表明,唐氏综合征(DS)患者存在慢性氧化应激。这些患者在30多岁和40多岁时大脑会出现类似阿尔茨海默病的变化。自身免疫性疾病和白内障的发病率显著增加,整体衰老过程加速。体外研究表明,简单的化学抗氧化剂,如维生素E、丁基羟基甲苯(BHT)和没食子酸丙酯,可以改善DS神经元的活力受损,这清楚地表明氧自由基参与其中。然而,由于缺乏体内实验,氧化应激在DS中的作用仍存在争议。我们在此报告了对166名个体尿液样本的化学分析结果,其中DS受试者与他们的兄弟姐妹进行了匹配。DNA氧化损伤的生物标志物8-羟基-2'-脱氧鸟苷(DS组为2.35±1.69,对照组为1.35±1.04,P = 0.00011)以及脂质过氧化的生物标志物丙二醛(DS组为0.255±0.158,对照组为0.20