Abstract
Huperzine A (HupA) and donepezil, two novel selective acetylcholinesterase inhibitors available for Alzheimer's disease, were tested for their ability to alleviate injury from oxygen-glucose deprivation (OGD) in the rat pheochromocytoma line PC12 cells. OGD for 30 min triggered death in more than 50% of cells, along with major changes in morphology and biochemistry including elevated levels of lipid peroxide, superoxide disamutase activity and lactate. Cells pretreated for 2 h with HupA or donepezil showed improved survival and reduced biochemical and morphologic signs of toxicity (statistically significant over the range from 10 microM down to 1.0 and 0.1 microM, respectively). Our results indicated that HupA and donepezil protected PC12 cells against OGD-induced toxicity, most likely by alleviating disturbances of oxidative and energy metabolism.
MeSH terms
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Alkaloids
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Alzheimer Disease / physiopathology
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Animals
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Cell Size / drug effects
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Cell Size / physiology
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Cell Survival / drug effects
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Cell Survival / physiology
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Cholinesterase Inhibitors / pharmacology*
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Donepezil
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Dose-Response Relationship, Drug
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Glucose / deficiency*
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Hypoxia-Ischemia, Brain / drug therapy*
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Hypoxia-Ischemia, Brain / metabolism
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Hypoxia-Ischemia, Brain / physiopathology
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Indans / pharmacology*
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Lipid Peroxidation / drug effects
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Lipid Peroxidation / physiology
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Malondialdehyde / metabolism
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Neuroprotective Agents / pharmacology*
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Oxidative Stress / drug effects
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Oxidative Stress / physiology
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PC12 Cells / cytology
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PC12 Cells / drug effects
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PC12 Cells / metabolism
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Piperidines / pharmacology*
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Rats
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Sesquiterpenes / pharmacology*
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Superoxide Dismutase / drug effects
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Superoxide Dismutase / metabolism
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Tetrazolium Salts / pharmacokinetics
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Thiazoles / pharmacokinetics
Substances
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Alkaloids
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Cholinesterase Inhibitors
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Indans
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Neuroprotective Agents
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Piperidines
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Sesquiterpenes
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Tetrazolium Salts
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Thiazoles
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huperzine A
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Malondialdehyde
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Donepezil
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Superoxide Dismutase
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thiazolyl blue
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Glucose