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

## TL;DR

This study shows that giving GCEE to rats with brain injuries helps restore key energy-related proteins by boosting antioxidant levels.

## Contribution

The study demonstrates GCEE's potential to restore enzymatic activity post-TBI through GSH elevation.

## Key findings

- GCEE administration increased enzymatic activity in energy-related proteins post-TBI.
- GCEE elevated GSH levels, which combats oxidative stress after brain injury.
- The therapeutic effect of GCEE was observed in Wistar rats with moderate TBI.

## Abstract

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.