Noninvasive Monitoring of Hepatic Glutathione Depletion Through Blood Test

通过血液检测无创监测肝脏谷胱甘肽消耗情况

• 批准号: 10230423
• 负责人: Jie Zheng
• 金额: $ 36.66万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10230423
• 关键词: Affect; Affinity; Alkaline Phosphatase; American; Animals; Antioxidants; Aspartate Transaminase; Biochemical; Biological Markers; Blood; Blood Circulation; Blood Tests; Cell Death; Chemistry; Clinic; Clinical; Clinical Research; Communicable Diseases; Consumption; Cysteine; Cystine; Diagnosis; Discontinuous Capillary; Disease; Disease Management; Disease Progression; Disease model; Dyes; Early Diagnosis; Early Intervention; Early treatment; Ensure; Event; Excision; Fluorescence; Foundations; Future; Glutathione; Gold; Hepatic; Hepatocyte; Immunologic Deficiency Syndromes; Indocyanine Green; Kidney; Laboratories; Liver; Liver diseases; Magnetic Resonance Spectroscopy; Measures; Mediating; Modeling; Monitor; Monkeys; Mus; Nanotechnology; Nature; Organ; Oxidation-Reduction; Oxidative Stress; Parkinson Disease; Particle Size; Pilot Projects; Plasma; Predisposition; Prevention; Process; Renal clearance function; Reporting; Resources; Serum; Serum Markers; Serum Proteins; Signal Transduction; Solid; Specificity; Stream; Sulfhydryl Compounds; Surface; Tissues; Transaminases; Translations; base; biomaterial compatibility; chronic liver disease; chronic liver injury; clinical practice; high risk; innovation; instrumentation; liver injury; mouse model; nano; nanoGold; nanocluster; nanoprobe; non-alcoholic fatty liver disease; non-invasive monitor; nonalcoholic steatohepatitis; novel; nuclear imaging; pre-clinical research; prevent; rapid technique; skills; success; tool

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.

摘要 谷胱甘肽（GSH）是体内主要的抗氧化剂，主要由肝细胞产生。恒定 肝谷胱甘肽流出到血流中允许整个身体的氧化还原电位被精确地 控制。因此，肝谷胱甘肽的耗竭与增加的易感性密切相关 氧化应激和许多疾病的高风险，如肝损伤，免疫缺陷，帕金森病 和传染病。然而，由于肝谷胱甘肽在血浆中被稀释了两个以上的数量级， 并被不同的器官消耗，与传统的肝脏血清生物标志物不同， 即使血液检测可以用来预测疾病， 比传统的血清标志物更早地进展。到目前为止，在临床前研究中， 的动物必须被处死;以便可以收集新鲜的肝组织用于离体定量肝细胞的增殖。 谷胱甘肽水平在临床研究中，C13磁共振波谱（MRS）和核成像是 正在开发间接测量GSH水平;然而，这种高端仪器和特殊技能 排除实验室对肝脏谷胱甘肽耗竭的病理生理学意义的解释 特别是那些资源有限的诊所，以便早期疾病管理。的目的 一项提议是开发一种创新的纳米技术，使血液检测成为一种简单而有效的方法， 用于无创和连续监测肝脏谷胱甘肽耗竭的快速工具; 通过血液测试，可以在诊所容易地监测消耗，并用作 肝脏和其他氧化应激相关疾病的诊断，这些疾病影响着数亿人的健康。 世界上的人。