期刊
REDOX BIOLOGY
卷 11, 期 -, 页码 631-636出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2017.01.014
关键词
Glutathione; Glutamylcysteine; Clinical trial; Homeostasis
资金
- University of New South Wales
Objective: To determine if orally dosed gamma-glutamylcysteine (gamma-GC) can increase cellular glutathione (GSH) levels above homeostasis. Many chronic and age-related disorders are associated with down-regulation, or impairment, of glutamate cysteine ligase (GCL). This suggests that gamma-GC supply may become limiting for the maintenance of cellular GSH at the normal levels required to effectively protect against oxidative stress and any resulting physiological damage. Methods: GSH levels were measured in lymphocytes of healthy, non-fasting participants before and after single oral doses (2 and 4 g) of gamma-GC. Blood samples were immediately processed using high speed fluorescence-activated cell sorting to isolate 106 lymphocytes that were then assayed for GSH content. Results: A single 2 g dose of gamma-GC increased lymphocyte GSH content above basal levels (53 +/- 47%, p < 0.01, n= 14) within 90 min of administration. A randomized dosage (2 and 4 g gamma-GC) crossover design was used to explore the pharmacokinetics of this GSH increase. In general, for both dose levels (n= 9), GSH increased from initial basal levels over 3 h (tmax) before reaching maximum GSH concentrations (C-max) that were near two (2 g gamma-GC) to three (4 g gamma-GC) fold basal levels (0.4 nmol/106 lymphocytes). Beyond tmax, GSH levels progressively declined reaching near basal levels by 5 h. The GSH half-life was between 2 and 3 h with exposure (AUC) to increased GSH levels of 0.7 (2 g gamma-GC) and 1.8 (4 g gamma-GC) nmol.h/10(6) lymphocytes. Conclusions: Oral gamma-GC is a non-toxic form of cysteine that can be directly taken up by cells and transiently increase lymphocyte GSH above homeostatic levels. Our findings that gamma-GC can increase GSH levels in healthy subjects suggests that it may have potential as an adjunct for treating diseases associated with chronic GSH depletion.
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