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 FeIIIDA2 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.

Mechanism Underlying the Effectiveness of Deferiprone in Alleviating Parkinson's Disease Symptoms.

Elevation in iron content as well as severe depletion of dopamine (DA) as a result of iron-induced loss of dopaminergic neurons has been recognized to accompany the progression of Parkinson's disease (PD). To better understand the mechanism of the mitigating effect of the iron chelator deferiprone (DFP) on PD, the interplay between iron and DFP was investigated both in the absence and presence of DA. The results show that DFP was extremely efficient in scavenging both aqueous iron and iron that was loosely bound to DA with the entrapment of iron in Fe-DFP complexed form critical to halting the iron catalyzed degradation of DA and associated generation of toxic metabolites. The DFP related scavenging of dopamine semiquinone (DA•-) and superoxide (O2•-) may also contribute to its positive effects in the treatment of PD.

Influence of Dissolved Silicate on Rates of Fe(II) Oxidation.

Increasing concentrations of dissolved silicate progressively retard Fe(II) oxidation kinetics in the circum-neutral pH range 6.0-7.0. As Si:Fe molar ratios increase from 0 to 2, the primary Fe(III) oxidation product transitions from lepidocrocite to a ferrihydrite/silica-ferrihydrite composite. Empirical results, supported by chemical kinetic modeling, indicated that the decreased heterogeneous oxidation rate was not due to differences in absolute Fe(II) sorption between the two solids types or competition for adsorption sites in the presence of silicate. Rather, competitive desorption experiments suggest Fe(II) was associated with more weakly bound, outer-sphere complexes on silica-ferrihydrite compared to lepidocrocite. A reduction in extent of inner-sphere Fe(II) complexation on silica-ferrihydrite confers a decreased ability for Fe(II) to undergo surface-induced hydrolysis via electronic configuration alterations, thereby inhibiting the heterogeneous Fe(II) oxidation mechanism. Water samples from a legacy radioactive waste site (Little Forest, Australia) were shown to exhibit a similar pattern of Fe(II) oxidation retardation derived from elevated silicate concentrations. These findings have important implications for contaminant migration at this site as well as a variety of other groundwater/high silicate containing natural and engineered sites that might undergo iron redox fluctuations.