Mustafa Shukry, Tarek Kamal, Radi Ali, Foad Farrag, Essam Almadaly, Ayman A Saleh, Mohammed Abu El-Magd
الملخص العربي
Activators of both adenosine 59-triphosphate (ATP)-sensitive Kz (KATP) channel and cystic fibrosis
transmembrane conductance regulator (CFTR) Cl{ channel have significant in vivo and in vitro
neuroprotection against glutamate-induced death of some neuronal cells. Here, the effect of the KATP channel
activator, pinacidil, and the CFTR Cl{ channel opener, levamisole, against glutamate-induced
oxidative stress were investigated in mouse hippocampal cells, HT22. The results from cell viability assay
(WST-1) showed that pinacidil and levamisole weakly protected cells against glutamate-induced toxicity at
10 mMand their effect increasedin a dose-dependentmanner till reachmaximumprotection at 300 mM.Pretreatment
with pinacidil or levamisole significantly suppressed the elevation of reactive oxygen species (ROS)
triggered by glutamate through stabilising mitochondrial membrane potential and subsequently protected
HT22 cells against glutamate-induced death. HT22 cells viability was maintained by pinacidil and levamisole
in presence of glutathione inhibitor, BSO. Also, pinacidil and levamisole pretreatment did not induce
recovery of glutathione levels decreased by glutamate. Expectedly, this protection was abolished by the KATP
and CFTR Cl{ channels blocker, glibenclamide. Thus, both pinacidil and levamisole protect HT22 cells
against glutamate-induced cell death through stabilising mitochondrial membrane potential and subsequently
decreasing ROS production.
محمد رزق ابو المجد الغنام | Mohammed Rizk Abu El-Magd El-Ghannam | 8901