Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 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 D1/D2-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 microM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H2O2 (0.6 mM) and the neurotoxin 6-hydroxydopamine (150 microM). Neither of these effects were exhibited by ascorbic acid, desferal, lisuride, or bromocriptine. Although pergolide exhibited some protection of PC12 cells against H2O2 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.
Gassen
M
M
Merck KGaA, Biomedical Research CNS, Darmstadt, Germany.
Gross
A
A
Youdim
M B
MB
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D011292:Premedication; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D001058:Apomorphine