Neuroprotective effects of nicergoline in immortalized neurons

We studied the potential neuroprotective action of nicergoline in immortali zed hypothalamic GT1-7 cells exposed to agents which deplete levels of redu ced glutathione, thus causing oxidative stress and cell death. Treatment wi th diethylmaleate (1 mM), buthionine sulfoximine (500 mu M) or menadione (1 0-50 mu M) caused diffuse GT1-7 cell degeneration, as assessed by using eit her the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay or the fluorescent dyes fluorescein diacetate and propid ium iodide. Pre- and/or co-exposure of the cells to nicergoline significant ly prevented diethylmaleate- or buthionine sulfoximine-induced neuronal dea th, whereas nicergoline was ineffective against menadione-induced toxicity. This effect was concentration-dependent and was mimicked by the classical antioxidants idebenone and vitamin E, and did not depend on interference wi th protein kinase C. Interestingly, the antineurodegenerative activity of n icergoline and Vitamin E or idebenone was not additive, suggesting that the se compounds share some intracellular mechanism(s) responsible for their pr otective effects. In conclusion, the present data indicate that nicergoline has neuroprotective activity, possibly mediated by the antioxidant activit y of the molecule, and give support to the potential use of nicergoline in the prevention and therapy of neurodegenerative diseases. (C) 1999 Elsevier Science B.V. All rights reserved.