Huperzine A and donepezil protect rat pheochromocytoma cells against oxygen-glucose deprivation.
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.
Zhou
J
J
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-yuan Road, 200031, Shanghai, People's Republic of China.
Fu
Y
Y
Tang
X C
XC
D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013778:Tetrazolium Salts / Q000493:pharmacokinetics; D013844:Thiazoles / Q000493:pharmacokinetics
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D012717:Sesquiterpenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C050426:huperzine A; D008315:Malondialdehyde; D000077265:Donepezil; D013482:Superoxide Dismutase; C022616:thiazolyl blue; D005947:Glucose