Noninvasive Monitoring of Hepatic Glutathione Depletion Through Blood Test

摘要 谷胱甘肽(GSH)是人体内主要的抗氧化剂，主要由肝细胞产生。常量 肝脏谷胱甘肽流入血流使整个身体的氧化还原电位 控制住了。因此，肝脏谷胱甘肽的耗竭已被发现与易感性的增加密切相关。 氧化应激和许多疾病的高风险，如肝损伤、免疫缺陷、帕金森氏病 和传染病。然而，由于肝脏谷胱甘肽在血浆中稀释了两个数量级以上 与传统的肝血清生物标记物不同，这一关键的病理生理 即使可以用来预测疾病，也不能很容易地通过血液检测来监测事件 进展比传统的血清标志物要早得多。到目前为止，在临床前研究中，大量 的动物；这样就可以收集新鲜的肝脏组织，用于体外量化 谷胱甘肽水平。在临床研究中，C13磁共振波谱(MRS)和核成像 正在开发以间接测量GSH水平；然而，这种高端仪器和特殊技能组合 排除实验室翻译肝脏谷胱甘肽耗竭的病理生理学意义 进入诊所，特别是那些资源有限的诊所，以便进行早期疾病管理。这样做的目的是 建议是开发一种创新的纳米技术，使血液检测成为一种简单和 无创连续监测肝脏谷胱甘肽耗竭的快速工具；使肝脏谷胱甘肽 在诊所通过血液测试可以很容易地监测到消耗情况，并可作为早期指标 诊断肝脏和其他与氧化应激相关的疾病，这些疾病正在影响数亿人 世界上的人们。

Abstract Glutathione (GSH) is the master antioxidant in the body and mainly produced in hepatocytes. Constant efflux of hepatic glutathione into the blood stream allows the redox potential of the entire body to be precisely controlled. Thus, depletion of hepatic glutathione has found to strongly correlate with an increased susceptibility to oxidative stress and high risk of many diseases such as liver injuries, immunodeficiency, Parkinson’s disease and infectious diseases. However, since hepatic glutathione is diluted more than two orders in the blood plasma and consumed by different organs, unlike conventional liver serum biomarkers, this crucial pathophysiological event cannot be readily monitored through blood testing even through it could be used to predict disease progression much earlier than conventional serum markers. Until now, in the preclinical research, a large number of animals have to be sacrificed; so that fresh liver tissues can be collected for ex vivo quantification of the glutathione level. In clinical research, C13 magnetic resonance spectroscopy (MRS) and nuclear imaging are being developed to indirectly measure GSH level; however, such high-end instrumentation and special skill sets preclude the translation of the pathophysiological significance of hepatic glutathione depletion from laboratories into the clinics, in particular, those with limited resources, for early disease management. The objective of this proposal is to develop an innovative nanotechnology that empowers blood testing to serve as a simple and rapid tool for noninvasive and consecutive monitoring of hepatic glutathione depletion; so that hepatic glutathione depletion could be readily monitored in the clinics through blood test and be used as an earlier indicator for diagnosis of liver and other oxidative-stress related diseases, which are influencing hundreds of millions of people in the world.