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 pheoc hromocytoma line PC12 cells. OGD for 30 min triggered death in more than 50 % of cells, along with major changes in morphology and biochemistry includi ng elevated levels of lipid peroxide, superoxide disamutase activity and la ctate. Cells pretreated for 2 h with HupA or donepezil showed improved surv ival and reduced biochemical and morphologic signs of toxicity (statistical ly significant over the range from 10 muM down to 1.0 and 0.1 muM, respecti vely). Our results indicated that HupA and donepezil protected PC12 cells a gainst OGD-induced toxicity, most likely by alleviating disturbances of oxi dative and energy metabolism. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.