Effect of gamma-glutamylcysteine ethylester on the levels of c-fos mRNA expression, glutathione and reactive oxygen species formation in kainic acid excitotoxicity.

Objectives: The aim of this study was to investigate the effect of gamma-glutamylcysteine ethylester (GCEE), a precursor of glutathione biosynthesis, on the levels of glutathione, formation of reactive oxygen species and c-fos mRNA expression in rat hippocampus and cortex in kainic acid-induced excitotoxicity.

Methods: Sprague-Dawley rats were used and divided into four groups: control, kainic acid (10 mg/kg), GCEE (10 mg/kg) and kainic acid (10 mg/kg) + GCEE (10 mg/kg). Kainic acid and GCEE were administered to the rats intraperitoneally. The levels of glutathione and the expressions of c-fos mRNA in hippocampus and cortex tissues were determined using spectrophotometric and reverse transcription followed real-time PCR methods, respectively. Formation of reactive oxygen species was determined using dichlorofluorescin fluorescence in brain synaptosomes treated with kainic acid or GCEE in vitro.

Key Findings: Kainic acid treatment significiantly upregulated the expression of c-fos mRNA in the hippocampus and cortex when compared to the control group. GCEE treatment significantly decreased the levels of c-fos mRNA in the cortex when compared to the kainic acid-treated group. GCEE treatment against kainic acid significantly increased the levels of glutathione in the cortex and hippocampus, and decreased the levels of formation of reactive oxygen species when compared to kainic acid-treated synaptosomes.

Conclusions: The increased levels of glutathione and the reduced levels of reactive oxygen species formation lead us to conclude that GCEE may be beneficial as a potential antioxidant against neurodegenerative processes where excitotoxicity is involved.