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

Abstract

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 μM of apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of H₂O₂ (0.6 mM) and the neurotoxin 6‐hydroxydopamine (150 μM). 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 not 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.