The effect of vitamin C and iron on dopamine-mediated free radical generation: implications to Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world. The oxidative stress and DA derived quinones have been proposed to be closely related to the progression of PD. To examine the possibility of the application of ascorbate (Asc) as a therapeutic strategy in PD, the effect of Asc on the fate of iron both in the absence and presence of DA was investigated. The results of this study indicate that, in the absence of iron, the presence of high concentrations of Asc is of great benefit in view of the alleviation in oxidative stress and formation of DA derived quinones by quenching radicals, such as O2 ˙- and DA˙- . As a well-known reductant, the presence of high concentrations of Asc in iron enriched solution results in elevation in the concentration of active Fe(ii), which poses a potential threat to health as a result of inefficient oxygenation. While a competition exists between Asc and DA, the higher affinity of DA towards iron coupled with the formation of the more stable FeIII DA2 complex renders Asc unlikely to reduce the DA bound iron. The results of this study suggest that while the application of Asc alone may aggravate the progression of PD in view of the possible peroxidation of Asc bound Fe(ii), a combination therapy of Asc and strong clinically used iron chelator would appear to be a promising direction for the treatment of PD as a result of the enhanced iron chelation and attenuation in oxidative stress and toxicity induced by DA derived quinones.