Potential neuroprotective effect of γ-glutamylcysteine ethyl ester on rat brain against kainic acid-induced excitotoxicity

Abstract

The aim of this study was to investigate the effect of γ-Glutamylcysteine Ethyl Ester (GCEE) on the levels of GSH, caspase-3 activity, DNA damage and the expressions of Bcl-2, Bax and p53 mRNAs in rat hippocampus after status epilepticus (SE) induced by systemic kainic acid (KA). The male rats were divided into four groups as controls, KA (10 mg/kg), GCEE (10 mg/kg) and KA+GCEE. Glutathione (GSH) levels and caspase-3 activity were determined spectrophotometrically and colourimetrically, respectively. DNA damage and Bcl-2, Bax and p53 mRNA expressions were quantified by comet assay and reverse transcription followed by RT-PCR, respectively. KA treatment significantly depleted GSH levels, induced DNA damage, caspase-3 activity and the expressions of p53 and Bax mRNA. GCEE treatment protected GSH levels, decreased DNA damage and the levels of p53 and Bax/Bcl-2 mRNA against KA injection. These results indicate that GCEE treatment at the dose of 10 mg/kg is capable to protect the depleted levels of GSH and shows an anti-apoptotic activity due to the decreased levels of apoptotic biomarkers in the rat hippocampus after SE induced by KA.

Keywords::

• Kainic acid
• γ-glutamylcysteine ethyl ester (GCEE)
• p53 mRNA
• Bcl-2 mRNA
• Bax mRNA
• DNA damage
• caspase-3 activity

Declaration of interest: This study was supported by the Technological and Scientific Council of Turkey (TUBITAK) (SBAG-K69-104S280 to A.Y). G.A and E.T were also supported by doctoral grants from TUBITAK. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 3 March 2010.