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

Free Radic Res. 2010 May;44(5):513-21. doi: 10.3109/10715761003645964.

Abstract

The aim of this study was to investigate the effect of gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • DNA Damage
  • Dipeptides / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Kainic Acid / toxicity*
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Dipeptides
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • N-gamma-glutamylcysteine ethyl ester
  • Kainic Acid