Konradi C, Riederer P, Youdim M B
J Neural Transm Suppl. 1986;22:61-73.
The effect of hydrogen peroxide on monoamine oxidase (MAO) activity has been determined in homogenates of human brain areas taken postmortem. It could be shown that hydrogen peroxide enhances significantly the activity of MAO-B after short-term incubation (2 min), while no changes have been noted after long-term preincubation (60 min) indicating reversibility of this effect. MAO-A activity was not changed or decreased after preincubation with hydrogen peroxide. Freezing and thawing procedures did not change hydrogen peroxide stimulation of MAO in the caudate nucleus, while MAO-A activity dose dependently decreased. Inhibition of hydrogen peroxide stimulated MAO-B activity in human cortex by (-)deprenyl was found to be of similar potency compared to hydrogen peroxide free estimations. Glutathione, ascorbic acid and mannitol did not block MAO stimulation by hydrogen peroxide, while sodium azide led to a complete inhibition of hydrogen peroxide derived MAO activitation. Interorgan comparison showed increase of MAO-B activity in crude mitochondrial fractions of rat liver after preincubation with hydrogen peroxide, while with rat heart a reduction of MAO activity was detectable. As a conclusion these data indicate a possible role of hydrogen peroxide in the age-dependent increase of MAO-B in platelets and brain. Furthermore, increase of cytotoxic hydrogen peroxide via combined L-dopa therapy cannot be excluded to be of importance in the appearance of adverse reactions after long-term treatment with high doses. To reduce hydrogen peroxide production due to MAO activity, a combined treatment of L-dopa plus a selective MAO inhibitor and eventually additional administration of radical scavengers (ascorbic acid, vitamin E etc.) seems to be indicated.
已在死后获取的人脑区域匀浆中测定了过氧化氢对单胺氧化酶(MAO)活性的影响。结果表明,短期孵育(2分钟)后过氧化氢可显著增强MAO-B的活性,而长期预孵育(60分钟)后未观察到变化,表明该效应具有可逆性。用过氧化氢预孵育后,MAO-A活性未改变或降低。冷冻和解冻程序未改变过氧化氢对尾状核中MAO的刺激作用,而MAO-A活性呈剂量依赖性降低。发现(-)司来吉兰对过氧化氢刺激的人皮质中MAO-B活性的抑制作用与无过氧化氢时的测定结果效力相似。谷胱甘肽、抗坏血酸和甘露醇不能阻断过氧化氢对MAO的刺激,而叠氮化钠可导致过氧化氢诱导的MAO激活完全被抑制。器官间比较显示,用过氧化氢预孵育后,大鼠肝脏粗线粒体部分中MAO-B活性增加,而在大鼠心脏中可检测到MAO活性降低。总之,这些数据表明过氧化氢可能在血小板和脑中MAO-B随年龄增长而增加中起作用。此外,长期高剂量治疗后出现不良反应时,不能排除通过联合左旋多巴治疗增加细胞毒性过氧化氢具有重要意义。为减少因MAO活性产生的过氧化氢,似乎应采用左旋多巴加选择性MAO抑制剂联合治疗,并最终额外给予自由基清除剂(抗坏血酸、维生素E等)。