Elucidation of the interplay between Fe(II), Fe(III), and dopamine with relevance to iron solubilization and reactive oxygen species generation by catecholamines

The non‐enzymatically catalyzed oxidation of dopamine (DA) and the resultant formation of powerful oxidants such as the hydroxyl radical ((•) OH) through ‘Fenton chemistry’ in the presence of iron within dopaminergic neurons are thought to contribute to the damage of cells or even lead to neuronal degenerative diseases such as Parkinson's disease. An understanding of DA oxidation as well as the transformation of the intermediates that are formed in the presence of iron under physiological conditions is critical to understanding the mechanism of DA and iron induced oxidative stress. In this study, the generation of H(2)O(2) through the autoxidation and iron‐catalyzed oxidation of DA, the formation of the dominant complex via the direct reaction with Fe(II) and Fe(III) in both oxygen saturated and deoxygenated conditions and the oxidation of Fe(II) in the presence of DA at physiological pH 7.4 were investigated. The oxidation of DA resulted in the generation of significant amounts of H(2)O(2) with this process accelerated significantly in the presence of Fe(II) and Fe(III). At high DA:Fe(II) ratios, the results from this study suggest that DA plays a protective role by complexing Fe(II) and preventing it from reacting with the generated H(2)O(2). However, the accumulation of H(2)O(2) may result in cellular damage as high intracellular H(2)O(2) concentrations will result in the oxidation of remaining Fe(II) mainly through the peroxidation pathway. At low DA:Fe(II) ratios however, it is likely that DA will act as a pro‐oxidant by generating H(2)O(2) which, in the presence of Fe(II), will result in the production of strongly oxidizing (•) OH radicals. [Image: see text]Powerful oxidants such as the hydroxyl radical ((•)OH) have previously been thought to be generated through the interplay between dopamine (DA) and iron, contributing to damage to cells and, potentially, leading to neuronal degenerative diseases such as Parkinson's disease. Our results suggest that DA plays a dual role as high DA/Fe(II) ratios prevent Fe(II) from reacting with the generated H(2)O(2) thereby reducing (•)OH generation, whereas low DA/Fe(II) ratios enhance (•)OH generation as a result of reaction of unbound Fe(II) and H(2)O(2) produced via both autoxidation and iron‐catalyzed oxidation of DA.