Potential neuroprotective effect of gamma-glutamylcysteine ethyl ester on rat brain against kainic acid-induced excitotoxicity.
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.
Yalcin
Ayfer
A
Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100 Bornova, Izmir, Turkey. ayfer.yalcin@ege.edu.tr
Armagan
Guliz
G
Turunc
Ezgi
E
Konyalioglu
Sibel
S
Kanit
Lutfiye
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004249:DNA Damage; D004151:Dipeptides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494828:Bax protein, rat; D004151:Dipeptides; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C067744:N-gamma-glutamylcysteine ethyl ester; D007608:Kainic Acid