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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.

摘要