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: 10552664
• 负责人: Jie Zheng
• 金额: $ 36.01万
• 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/10552664
• 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; Dissociation; 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; Measures; Mediating; Modeling; Monitor; Monkeys; Mus; NMR Spectroscopy; Nanotechnology; Nature; Organ; Oxidation-Reduction; Oxidative Stress; Parkinson Disease; Particle Size; Persons; 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; biomaterial compatibility; chronic liver disease; chronic liver injury; clinical practice; empowerment; 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.

抽象的 谷胱甘肽（GSH）是体内的主要抗氧化剂，主要在肝细胞中产生。持续的 肝谷胱甘肽向血液的外流允许整个身体的氧化还原电势精确 受控。肝谷胱甘肽的耗尽已发现与易感性增加密切相关 氧化应激和许多疾病的高风险，例如肝损伤，免疫缺陷，帕金森氏病 和传染病。但是，由于肝谷胱甘肽在血浆中被稀释了两个以上的顺序 与常规肝血清生物标志物不同，这是由不同的器官食用的，这种关键的病理生理学 即使通过血液测试也不能轻易监测事件，即使可以用来预测疾病 进展要早得多。到目前为止，在临床前研究中，很多 必须牺牲动物；因此，可以收集新鲜的肝组织以进行体内定量 谷胱甘肽水平。在临床研究中，C13磁共振光谱（MRS）和核成像是 开发以间接测量GSH水平；但是，这样的高端仪器和特殊技能 排除实验室肝谷胱甘肽消耗的病理生理意义的翻译 特别是进入诊所，有限的资源来进行早期疾病管理。这个目的 提案是开发一种创新的纳米技术，该学赋予血液测试的能力，以作为一种简单而简单的 快速对肝谷胱甘肽无创和连续监测的工具；这样的肝谷胱甘肽 可以通过血液检查在诊所中很容易监测耗竭，并用作早期的指标 肝脏和其他氧化应力相关疾病的诊断，这些疾病影响了数亿 世界上的人。