Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H 2 O 2 and 6‐Hydroxydopamine

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...

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Veröffentlicht in:Movement disorders 1998-07, Vol.13 (4), p.661-667
Hauptverfasser: Gassen, Michael, Gross, Aviva, Youdim, Moussa B. H.
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Sprache:eng
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Zusammenfassung: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 µM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H 2 O 2 (0.6 mM) and the neurotoxin 6‐hydroxydopamine (150 µM). Neither of these effects were exhibited by ascorbic acid, desferal, lisuride, or bromocriptine. Although pergolide exhibited some protection of PC12 cells against H 2 O 2 toxicity, it was not as potent as apomorphine. In light of the present findings and the clinical reports that parkinsonian patients on long‐term apomorphine therapy stabilize clinically and can be weaned off L ‐dopa, one may assume that apomorphine can exert a neuroprotective activity by way of its potent antioxidant properties.
ISSN:0885-3185
1531-8257
DOI:10.1002/mds.870130409