title: Pinacidil and levamisole prevent glutamate-induced death of hippocampal neuronal cells through reducing ROS production.
abstract: Activators of both adenosine 5'-triphosphate (ATP)-sensitive K(+) (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 μM and their effect increased in a dose-dependent manner till reach maximum protection at 300 μM. 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.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Shukry
authors.forename: Tarek
authors.initials: T
authors.lastname: Kamal
authors.forename: Radi
authors.initials: R
authors.lastname: Ali
authors.forename: Foad
authors.initials: F
authors.lastname: Farrag
authors.forename: Essam
authors.initials: E
authors.lastname: Almadaly
authors.forename: Ayman A
authors.initials: AA
authors.lastname: Saleh
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abu El-Magd
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists; D007978:Levamisole / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020110:Pinacidil / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D054086:KATP Channels; D017382:Reactive Oxygen Species; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007978:Levamisole; D018698:Glutamic Acid; D020110:Pinacidil
keywords: CFTR Cl−  ,; Glutathione,; HT22; KATP ,; Levamisole,; Pinacidil,; ROS,