Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine

被引:87
作者
Gassen, M [1 ]
Gross, A [1 ]
Youdim, MBH [1 ]
机构
[1] Technion Israel Inst Technol, Fac Med,Ctr Neurodegenerat Dis, Dept Pharmacol,Eve Topf & Natl Parkinsons Fdn, Bruce Rappaport Family Res Inst, IL-31096 Haifa, Israel
关键词
apomorphine; Parkinson's disease; free radicals; antioxidants; iron chelation; PC12; cells; neuroprotection;
D O I
10.1002/mds.870130208
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
A significant body of evidence has been provided to support the hypothesis that oxidant stress may be responsible For the degeneration of dopaminergic neurons in the substantia nigra pars compacta in Parkinson's disease. Apomorphine, a dopamine D-1/D-2-receptor agonist in the clinical therapy of Parkinson's disease, has been found to be a potent antioxidant and to prevent free radical reaction in rat brain mitochondrial fraction. In this article we show that 1-10 mu M of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H2O2 (0.6 mM) and the neurotoxin 6-hydroxydopamine (150 mu M) These effects were not exhibited by ascorbic acid, desferal, lisuride, or bromocriptine. Although pergolide exhibited some protection of PC12 cells against H2O2 toxicity, it was nut as potent as apomorphine. In light of the present findings and the clinical reports that parkinsonian patients on long-term apomorphine stabilize clinically and can be weaned off L-dopa, one may assume that apomorphine can exert a neuroprotective activity via its potent antioxidant properties.
引用
收藏
页码:242 / 248
页数:7
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