School of Civil and Environmental Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
Dalton Trans. 2018 Mar 28;47(12):4059-4069. doi: 10.1039/c7dt04373b. Epub 2018 Feb 6.
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 O˙ 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 FeDA 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.
帕金森病（PD）是世界上第二常见的神经退行性疾病。氧化应激和多巴胺衍生的醌已被提出与 PD 的进展密切相关。为了研究抗坏血酸（Asc）作为 PD 治疗策略的应用可能性，研究了 Asc 在没有和存在多巴胺的情况下对铁命运的影响。这项研究的结果表明，在没有铁的情况下，高浓度的 Asc 的存在具有很大的好处，因为它可以缓解氧化应激和通过淬灭自由基（如 O˙和 DA˙）形成多巴胺衍生的醌。作为一种众所周知的还原剂，在富含铁的溶液中存在高浓度的 Asc 会导致活性 Fe（ii）浓度升高，由于氧气化效率低下，这对健康构成潜在威胁。虽然 Asc 和多巴胺之间存在竞争，但多巴胺对铁的亲和力更高，并且形成更稳定的 FeDA 配合物，使得 Asc 不太可能还原与多巴胺结合的铁。这项研究的结果表明，尽管单独应用 Asc 可能会由于 Asc 结合的 Fe（ii）的可能过氧化而加重 PD 的进展，但 Asc 和临床上常用的强铁螯合剂的联合治疗似乎是治疗 PD 的一个有前途的方向，因为它增强了铁螯合作用，并减轻了由多巴胺衍生的醌引起的氧化应激和毒性。
