Determination of Gamma-Glutamylcysteine Ethyl Ester Efficacy Using Enzymatic Analysis and Proteomic Investigation of Oxidatively Modified Proteins in Moderate Traumatic Brain Injury

Traumatic brain injury (TBI) affects millions of people worldwide, with approximately 1.7 million cases occurring in the United States each year1. These injuries may be mild, moderate, or severe based on intensity of impact. The damage caused by TBI is not only caused by initial damage, but also secondary damage resulting from oxidative stress. Oxidative stress is the increase in reactive oxygen and nitrogen species and the decrease in overall antioxidant capacity, which can lead to a loss of protein function. There is currently no treatment for TBI, only alleviation of symptoms. Since TBI is a spontaneous event, post-therapeutic strategies would be most beneficial to investigate. Glutathione, the most potent antioxidant in the brain, is capable of reducing oxidative damage. This study investigates the efficacy of gamma-glutamylcysteine ethyl ester (GCEE), a glutathione analog, as a post-therapeutic treatment option in moderate TBI using enzymatic analysis and proteomic investigation. Enzymatic analysis indicates that key metabolic enzymes of TBI samples treated with GCEE significantly increase in activity relative to TBI samples with a saline treatment. Protein and gene expression of TBI samples treated with GCEE was also analyzed and compared to that of control and saline-treated samples. Results demonstrate GCEE as a promising post-therapeutic treatment for moderate TBI. References 1. Coronado, V. G.; Xu, L.; Basavaraju, S. V.; et al, Surveillance for traumatic brain injury-related deaths: United States, 1997-2007. US Department of Health and Human Services, Centers for Disease Control and Prevention Atlanta: 2011