The effects of glutathione and ascorbic acid on the oxidations of 6-hydroxydopa and 6-hydroxydopamine.
The effects of glutathione and ascorbic acid on the oxidations of 6-hydroxydopa and 6-hydroxydopamine.
复制标题
DOI：
10.1016/0304-4165(94)90082-5
复制
发表时间：
1994-12
期刊：
影响因子：
--
通讯作者：
A. Nappi;E. Vass
中科院分区：
文献类型：
--
作者：
A. Nappi;E. Vass
采用高效液相色谱-电化学检测（HPLC-ED）和光谱法研究了抗坏血酸（AA）和还原性谷胱甘肽（GSH）在儿茶酚胺能神经毒素6-羟多巴胺（TOPA）和6-羟多巴胺（6-OHDA）氧化过程中的相互作用。这些比较研究表明，TOPA和6-OHDA具有极强的AA性，而GSH不能显著阻碍这些三羟基苯基的氧化，也不能通过还原其氧化产物来再生这些物质，尽管这种氧化还原交换机制已被证明是AA和二羟基苯基多巴胺的交换机制。虽然GSH不能保持TOPA和6-OHDA为还原分子，但GSH可能通过与三羟基苯基氧化产物形成谷胱甘肽偶联物相互作用，从而影响三羟基苯基的神经毒性，从而将反应途径从潜在毒性的真黑素前体转向产生现象黑素。电化学分析确定了每个三羟基苯基产生两种氧化产物，一种在−100 mV下检测到，另一种在+ 700 mV下检测到。AA对两种氧化产物都没有影响，GSH显著降低了两种氧化产物的水平。在+ 700 mV下检测到的成分是环化的，还原的白色素。在−100 mV下检测到的成分的身份尚未确定，但它被认为是对醌或环化氧化的氨基色素。
The interactions of ascorbic acid (AA) and reduced glutathione (GSH) in the oxidations of the catecholaminergic neurotoxins 6-hydroxydopa (TOPA) and 6-hydroxydopamine (6-OHDA) were investigated by both high performance liquid chromatography with electrochemical detection (HPLC-ED) and spectrometric methods. These comparative studies showed TOPA and 6-OHDA to be extremely AA nor GSH was found capable of significantly impeding the oxidations of these trihydroxyphenyls, or of regenerating these substances by reducing back their oxidation products, even though such a redox exchange mechanism was demonstrated for AA and the dihydroxyphenyl dopamine. Although ineffective in keeping TOPA and 6-OHDA as reduced molecules, GSH may nevertheless influence the neurotoxicity of trihydroxyphenyls by interacting with their oxidation products forming glutathionyl conjugates, thereby switching the reaction pathway away from potentially toxic eumelanin precursors and toward the production of pheomelanin. Electrochemical analyses established the formation of two oxidation products derived from each trihydroxyphenyl, one detected at −100 mV and the other at + 700 mV. AA had no effect on either oxidation product, where GSH significantly decreased the levels of both oxidation products. The component detected at + 700 mV is the cyclized, reduced leukochrome. The identity of the component detected at −100 mV was not established, but it is considered to be either thep-quinone or the cyclized, oxidized aminochrome.