Van der Vliet A, O'Neil C A, Eiserich J P, Cross C E
Department of Internal Medicine, University of California, Davis 95616, USA.
Arch Biochem Biophys. 1995 Aug 1;321(1):43-50. doi: 10.1006/abbi.1995.1366.
Environmental levels of ozone (O3) frequently exceed air quality standards in many urban areas, and much research has been devoted to pathophysiological effects of O3 inhalation. Inhaled O3 will interact primarily with respiratory tract lining fluids (RTLF) and with constituents therein. It is believed that interaction of O3 with constituents in RTLF occurs by reactive absorption. We investigated interactions of O3 with human blood plasma, used as a model extracellular fluid representing RTLF, and studied oxidation of plasma antioxidants, proteins, and lipids. Plasma was exposed to various concentrations of O3 in humidified air, supplied at a continuous flow, in a system that mimics exposure of RTLF to inhaled O3 in vivo. Interaction of O3 with plasma appeared to be caused by reactive absorption of O3 by plasma. It was found that O3 reacts primarily with the aqueous antioxidants ascorbate and urate. Reactive absorption of O3 by plasma ascorbate and urate was found to be more efficient at low (2 ppm) O3 levels than at high (16 ppm) levels. We were also able to detect oxidative damage to plasma proteins and lipids after prolonged exposure to O3. Second, we investigated whether GSH or dihydrolipoic acid (DHLA) could prevent oxidative damage to plasma proteins and lipids by O3, under our exposure conditions. In contrast to plasma, RTLF contain relatively high amounts of GSH, which may contribute to antioxidant protection to respiratory tract epithelial cells. DHLA is an endogenous dithiol and has potent antioxidant properties. Addition of either GSH or DHLA to plasma (at concentrations up to 1 mM) prior to O3 exposure did not inhibit oxidation of plasma proteins and lipids during exposure to O3, nor did it attenuate depletion rates of ascorbate or urate. Our results indicate that added thiols cause increased reactive absorption of O3, rather than preventing reaction of O3 with other plasma constituents. Thiol supplementation could afford protection against O3-induced injury in vivo by increasing reactive absorption of O3 in the upper respiratory tract, thereby protecting the epithelia of lower airways and gas-exchanging portions of the lungs from exposure to toxic levels of O3.(ABSTRACT TRUNCATED AT 400 WORDS)
在许多城市地区，环境中的臭氧（O₃）水平经常超过空气质量标准，并且已有大量研究致力于吸入O₃的病理生理效应。吸入的O₃主要会与呼吸道内衬液（RTLF）及其所含成分发生相互作用。据信，O₃与RTLF中的成分通过反应性吸收发生相互作用。我们研究了O₃与用作代表RTLF的细胞外液模型的人血浆的相互作用，并研究了血浆抗氧化剂、蛋白质和脂质的氧化情况。在一个模拟RTLF在体内暴露于吸入O₃的系统中，将血浆暴露于以连续流动方式供应的潮湿空气中的各种浓度的O₃。O₃与血浆的相互作用似乎是由血浆对O₃的反应性吸收引起的。研究发现，O₃主要与水性抗氧化剂抗坏血酸盐和尿酸盐发生反应。已发现血浆抗坏血酸盐和尿酸盐对O₃的反应性吸收在低（2 ppm）O₃水平时比在高（16 ppm）水平时更有效。在长时间暴露于O₃后，我们还能够检测到血浆蛋白质和脂质的氧化损伤。其次，我们研究了在我们的暴露条件下，谷胱甘肽（GSH）或二氢硫辛酸（DHLA）是否可以预防O₃对血浆蛋白质和脂质的氧化损伤。与血浆不同，RTLF含有相对大量的GSH，这可能有助于对呼吸道上皮细胞的抗氧化保护。DHLA是一种内源性二硫醇，具有强大的抗氧化特性。在O₃暴露之前向血浆中添加GSH或DHLA（浓度高达1 mM），在暴露于O₃期间既没有抑制血浆蛋白质和脂质的氧化，也没有减弱抗坏血酸盐或尿酸盐的消耗速率。我们的结果表明，添加的硫醇会导致O₃的反应性吸收增加，而不是阻止O₃与其他血浆成分的反应。补充硫醇可以通过增加上呼吸道中O₃的反应性吸收，从而保护下呼吸道上皮和肺部气体交换部分免受有毒水平的O₃暴露，在体内提供针对O₃诱导损伤的保护。（摘要截断于400字）
