Abstract
Ebselen is a selenium compound that have glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. The efficacy of ebselen to prevent excitotoxicity provoked by glutamate in cerebellar granule neurons was investigated at various time points and concentrations. Simultaneous addition of ebselen with glutamate decreased neuronal death and was completely reversed by 3 microM of ebselen (3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and propidium iodide assays). However, when 1 microM of ebselen was added with glutamate and remained in the culture medium until 24 or 48 h, the neuronal survival increased to the control. The mechanism proposed for neuroprotection was the ability of ebselen to prevent lipoperoxidation provoked by glutamate. The present findings propose to amplify the use of ebselen in others neurodegenerative disorders involving glutamatergic system.
MeSH terms
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Animals
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Animals, Newborn
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Antioxidants / pharmacology*
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Azoles / pharmacology*
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Cell Survival / drug effects
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Cell Survival / physiology
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Cells, Cultured / cytology
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Cerebellar Cortex / cytology
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Cerebellar Cortex / drug effects
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Cerebellar Cortex / metabolism
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Dose-Response Relationship, Drug
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Glutamic Acid / metabolism*
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Glutamic Acid / pharmacology
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Isoindoles
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Lipid Peroxidation / drug effects
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Lipid Peroxidation / physiology
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / metabolism
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Nerve Degeneration / physiopathology
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Neurodegenerative Diseases / drug therapy
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / physiopathology
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Neuroprotective Agents / pharmacology*
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Neurotoxins / metabolism*
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Neurotoxins / pharmacology
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Organoselenium Compounds / pharmacology*
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Rats
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Rats, Wistar
Substances
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Antioxidants
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Azoles
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Isoindoles
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Neuroprotective Agents
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Neurotoxins
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Organoselenium Compounds
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Glutamic Acid
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ebselen