Autoxidation and various enzyme-mediated oxidations of the serotonergic neurotoxin 5,7-dihydroxytryptamine (1) give 5-hydroxytryptamine-4,7-dione (2) and 6,6'-bi(5-hydroxytryptamine-4,7-dione) (3) as the major products. When administered into the ventricular system of mice 2 and 3 are general toxins. The LD50 values for 2 (29.6 +/- 0.04 micrograms) and 3 (25.4 +/- 0.30 micrograms) are lower than that for 1 (51.8 +/- 0.28 micrograms). In the presence of cellular reductants (glutathione, cysteine, ascorbate) and molecular oxygen, or when incubated with rat brain homogenate, 2 and 3 redox cycle and form superoxide radical anion, O2.-, as a byproduct. The lethal effects of 2 and 3 when introduced into the brain may in part be due to such redox cycling reactions which deplete oxygen levels and, as a result of Haber-Weiss chemistry deriving from O2.-, form the cytotoxic hydroxyl radical (HO.). Intraventricular administration of 2 and 3 to mice causes only relatively minor and transient (ca. 1 h to 1 day) changes in whole brain levels of dopamine, 5-hydroxytryptamine (from both 2 and 3), acetylcholine, and choline (from 2 only). These changes differ from the profound and long-lasting serotonergic deficit evoked by 1. On the basis of these results a hypothesis has been formulated which proposes that the selective neurotoxicity of 1 derives from its rapid uptake into serotonergic neurons where it is oxidatively converted to 2 and 3. Redox cycling reactions of 2 and 3 then result in the depletion of intraneuronal oxygen and concomitant formation of O2.-. Dismutation of O2.- gives H2O2 which, as a result of transition metal ion-catalyzed Haber-Weiss chemistry, yields HO.. Thus, neuronal damage and death might result from the combined effects of hypoxia and HO. formation.

中文翻译：

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血清素神经毒素5,7-二羟基色胺的分子机制的进一步见解。

血清素神经毒素5,7-二羟基色胺（1）的自氧化作用和各种酶介导的氧化作用产生5-羟基色胺4,7-二酮（2）和6,6'-bi（5-羟基色胺-4,7-二酮） （3）作为主要产品。当施用于小鼠2和3的心室系统时，它们是一般毒素。2（29.6 +/- 0.04微克）和3（25.4 +/- 0.30微克）的LD50值低于1（51.8 +/- 0.28微克）的LD50值。在存在细胞还原剂（谷胱甘肽，半胱氨酸，抗坏血酸盐）和分子氧的情况下，或与大鼠脑匀浆一起孵育时，第2和3个氧化还原循环并形成超氧化物自由基阴离子O2-作为副产物。2和3进入大脑时的致命作用可能部分是由于这种氧化还原循环反应耗尽了氧气含量，并且是由于Haber-Weiss化学源自O2而产生的。-，形成细胞毒性羟基自由基（HO。）。对小鼠进行脑室内2和3给药只会引起全脑多巴胺，5-羟色胺（2和3均），乙酰胆碱和胆碱（仅2个）的相对较小且短暂的变化（约1小时至1天）。 ）。这些变化与1引起的严重而持久的血清素能缺乏症有所不同。基于这些结果，提出了一个假设，该假设提出1的选择性神经毒性源于其被快速氧化为2的血清素能神经元摄取。 3. 2和3的氧化还原循环反应会导致神经内氧耗竭并随之形成O2.-。O2.-的歧化产生H2O2，由于过渡金属离子催化的Haber-Weiss化学作用，H2O2产生HO ..因此，神经元损伤和死亡可能是由缺氧和HO共同作用引起的。编队。