Restoration of Enzymatic Activity of Energy-Related Proteins in Rats with Traumatic Brain Injury Following Administration of Gamma-Glutamylcysteine Ethyl Ester.

Background/

Objectives

Biochemical processes such as the glycolytic pathway and Kreb's cycle are important in producing ATP for the brain. Without a sufficient supply of glucose for energy metabolism, the brain cannot efficiently regulate or coordinate the actions and reactions of the body. It is well documented that traumatic brain injury (TBI) is associated with reduced energy metabolism through the production of reactive oxygen/nitrogen species. Antioxidants, such as glutathione (GSH), have been shown to combat the deleterious effects of oxidation by scavenging ROS/RNS, inhibiting propagation, and removing neurotoxic byproducts. Gamma-glutamylcysteine ethyl ester (GCEE), an ethyl ester moiety of gamma-glutamylcysteine, exhibits antioxidant activity by increasing GSH production. This therapeutic has protective effects against oxidative stress through the elevation of glutathione.

Methods

This study investigates the enzymatic activities of several key energy-related proteins that have been identified as nitrated in treated Wistar rats with moderate TBI. To test the hypothesis that the elevation of GSH production upon administration of GCEE will normalize enzymatic activity post-TBI, adult male Wistar rats were equally divided into three groups: sham, saline, and GCEE. Rats were treated with 150 mg/kg saline or GCEE at 30 and 60 min post-TBI. Upon sacrifice, brains were harvested and enzymatic activity was measured spectrophotometrically.

Results

An increase in enzymatic activity upon GSH elevation via GCEE administration in several key enzymes was observed.

Conclusions

GCEE is a potential therapeutic strategy to restore energy-related proteins in the brain post-TBI via GSH elevation.