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

基本信息

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
项目类别：
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

项目摘要

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）是体内主要的抗氧化剂，主要在肝细胞中产生。肝脏谷胱甘肽流入血流，使整个身体的氧化还原电位精确因此，已发现肝脏谷胱甘肽的消耗与易感性增加密切相关。氧化应激和许多疾病的高风险，如肝损伤、免疫缺陷、帕金森病然而，由于肝脏谷胱甘肽在血浆中被稀释超过两个数量级。并被不同的器官消耗，与传统的肝脏血清生物标志物不同，这种关键的病理生理学即使可以用来预测疾病，也无法通过血液检测轻松监测事件比传统的血清标志物早得多，直到现在，在临床前研究中，有大量的进展。必须处死动物，以便收集新鲜的肝组织用于离体定量在临床研究中，C13 磁共振波谱 (MRS) 和核成像是检测谷胱甘肽水平的方法。然而，此类高端仪器和特殊技能正在开发用于间接测量 GSH 水平；排除实验室对肝谷胱甘肽耗竭的病理生理学意义的翻译进入诊所，特别是那些资源有限的诊所，以进行早期疾病管理。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连续监测肝脏谷胱甘肽消耗的快速工具，以便肝脏谷胱甘肽消耗；可以在诊所通过血液测试轻松监测消耗情况，并用作早期指标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世界上的人们。