Critical Care Research Group, Southampton NIHR Biomedical Research Centre, Tremona Road, Southampton SO16 6YD, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
Clinical & Experimental Sciences, Faculty of Medicine, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK.
Redox Biol. 2019 Feb;21:101113. doi: 10.1016/j.redox.2019.101113. Epub 2019 Jan 22.
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this 'Reactive Species Interactome' (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable 'metabolic signatures' to a defined physiological challenge could potentially offer new avenues for personalised medicine.
活性氧（ROS）、氮（RNS）和硫（RSS）物种之间的化学和功能相互作用使生物体能够检测和响应代谢和环境应激源，如运动和海拔暴露。活性氧相互作用组（RSI）的氧化还原标志物和组成部分在动脉血和静脉血中的浓度是否不同尚不清楚。我们假设这些测量可能为整体水平的代谢/氧化还原调节提供有用的见解，并且在暴露于相同挑战的个体之间是一致的。在 2010 年的极限阿尔卑斯探险中进行了一项探索性研究，其中 4 名健康个体（2 名男性，2 名女性）在海平面和 4559 米处进行恒功心肺运动测试之前、期间和之后进行了配对的动脉和中心静脉采血。出乎意料的是，在整个运动过程中，血浆总游离巯基和游离半胱氨酸浓度在高海拔地区仍保持显著升高，动静脉梯度很小。只有在联合高海拔/运动应激下，游离硫化物浓度才会发生适度变化，而结合硫化物水平在高海拔地区低于海平面。没有观察到 4-羟基壬烯醛、异前列腺素、硝酸盐、亚硝酸盐、亚硝基物种和环鸟苷单磷酸等物质的预期氧化应激和硝酸盐→亚硝酸盐→NO 还原增加的一致信号。然而，观察到的动静脉浓度差异显示出每个参与者特有的动态反应模式。这种获得可量化“代谢特征”的新氧化还原代谢组学方法可能为个性化医疗提供新途径。
