Restoration of enzymatic activity of energy related proteins in traumatic brain injured rats following the administration of gamma‐glutamylcysteine ethyl ester

Abstract

The brain serves as the control center for the body. Its function is primarily dependent upon sufficient supply of glucose for energy metabolism. The glycolytic pathway and Kreb's cycle are important in producing ATP for the brain. Brain dysfunction resulting from an external force is known as traumatic brain injury (TBI). Symptoms range from physical to psychological and effects can be mild, moderate, or severe depending on the extent of the injury. TBI is associated with oxidative damage resulting in reduced energy metabolism. Antioxidants are substances responsible for the inhibition of oxidation. Gamma‐glutamylcysteine ethyl ester (GCEE) is an ethyl ester moiety of gamma‐glutamylcysteine that exhibits antioxidant activity by increasing glutathione production. This study investigates the enzymatic activity of two energy related enzymes, malate dehydrogenase and glyceraldehyde‐3‐phosphate dehydrogenase that have been identified as being nitrated in moderate TBI. To test the hypothesis that the administration of GCEE will normalize enzymatic activity post‐TBI, adult male Wistar rats were divided equally into three groups: Sham, Saline, and GCEE treatment (150 mg/kg). Upon sacrifice, enzymatic activity was indirectly measured spectrophotometrically by assessing the absorbance of reduced β‐nicotinamide adenine dinucleotide at 340nm. Preliminary data demonstrates that the administration of GCEE post‐TBI robustly increases enzymatic activity bolstering the hypothesis. These results are promising and indicate potential therapeutic strategies to restore enzymatic activity in the brain post‐TBI.