Endogenous urate production augments plasma antioxidant capacity in healthy, lowland subjects exposed to high altitude
Endogenous urate production augments plasma antioxidant capacity in healthy, lowland subjects exposed to high altitude
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DOI：
10.1378/chest.06-2235
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发表时间：
2007-05-01
期刊：
影响因子：
9.6
通讯作者：
Webb, David J.
中科院分区：
文献类型：
--
作者：
Baillie, J. Kenneth;Bates, Matthew G. D.;Webb, David J.
背景资料：体外组织缺氧和体内全身缺氧都能促进活性氧（ROS）的释放，这对心血管系统有潜在的损害。抗氧化系统保护免受ROS的氧化损伤，并可能对氧化刺激表现出一定程度的反应性。尿酸盐是一种有效的可溶性抗氧化剂，在缺氧条件下会增加。我们的目的是确定尿酸盐是否是一个重要的抗氧化防御健康受试者暴露于hypoxia.Methods：我们进行了一项队列研究，25名健康的低地志愿者在急性暴露于高海拔（4天在3,600英寸，然后在5,200英寸10天）的顶点高海拔研究考察玻利维亚。我们通过两种技术测量氧化应激标志物（8-异前列烷F2）、血清尿酸盐浓度和总血浆抗氧化活性：2，2 '-氨基-二-[3-乙基苯并噻唑磺酸盐]分光光度法（总抗氧化状态[TAS]）和增强化学发光法（ECL）。在高海拔1周后，TAS和ECL测定的血浆抗氧化能力（AOC）和血清尿酸盐浓度显著升高（与海平面相比，p < 0.01），F2-异前列烷水平降低至海平面水平。在此阶段，血浆尿酸与AOC之间存在高度显著的相关性（ECL，r（2）= 0.59，p = 0.0001; TAS，r（2）= 0.30，p = 0.0062）。
Background: Both tissue hypoxia in vitro, and whole-body hypoxia in vivo, have been found to promote the release of reactive oxygen species (ROS) that are potentially damaging to the cardiovascular system. Antioxidant systems protect against oxidative damage by ROS and may exhibit some degree of responsiveness to oxidative stimuli. Production of urate, a potent soluble antioxidant, is increased in hypoxic conditions. We aimed to determine whether urate is an important antioxidant defense in healthy subjects exposed to hypoxia.Methods: We conducted a cohort study of 25 healthy lowland volunteers during acute exposure to high altitude (4 days at 3,600 in, followed by 10 days at 5,200 in) on the Apex high-altitude research expedition to Bolivia. We measured markers of oxidative stress (8-isoprostane F2), serum urate concentration, and total plasma antioxidant activity by two techniques: 2,2'-amino-di-[3-ethylbenzthiazole sulfonate] spectrophotometry (total antioxidant status [TAS]) and enhanced chemiluminescence (ECL).Results: On ascent, F2-isoprostane levels were significantly elevated compared with those at sea level (p < 0.01). After 1 week at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and serum urate concentration were significantly elevated (each p < 0.01 vs sea level), and F2-isoprostane levels were reduced to values at sea level. There was a highly significant correlation between plasma urate and AOC at this stage (ECL, r(2) = 0.59, p = 0.0001; TAS, r(2) = 0.30, p = 0.0062).Conclusions: Our results support the hypothesis that urate may act as a responsive endogenous antioxidant in high-altitude hypoxia.