Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction
Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction
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DOI：
10.1016/0014-2999(96)00291-9
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发表时间：
1996-07-18
影响因子：
5
通讯作者：
Youdim, MBH
中科院分区：
文献类型：
--
作者：
Gassen, M;Glinka, Y;Youdim, MBH
麦角碱衍生的多巴胺受体激动剂，如培高利特或溴隐碱，最近作为潜在的神经保护药物引起了人们的注意。经典的混合型多巴胺D-1和D-2受体激动剂阿波啡，虽然在临床上用于治疗帕金森病，但从未检测过任何与神经保护相关的特性。本文研究了0.1 ~ 100 μ M阿波啡对大鼠线粒体抗坏血酸/铁刺激自由基过程的影响。亚微摩尔浓度的阿波啡（0.3 μ M加2.5 μ M Fe2+， 0.6 μ M加5.0 μ M Fe2+）可以完全抑制脂质过氧化，其效果是去铁胺的两倍多，是多巴胺的20倍。线粒体中脂质过氧化的抑制与阿波啡氧化率的增加有关。通常对抗氧化剂不太敏感的蛋白质羰基的形成可以被阿波啡显著地减少。在我们采用的模型系统中，阿波啡在阻止硫巴比妥反应性物质形成方面比多巴胺、去铁胺或培高利特更有效。反应的时间过程表明，阿波啡是一种自由基清除剂，其铁螯合性能可能不是很重要。由于氧化应激与帕金森病有关，阿波啡作为一种神经保护作用值得研究。
Ergoline-derived dopamine receptor agonists, like pergolide or bromocryptine, have recently attracted attention as potential neuroprotective drugs. The classical mixed type dopamine D-1 and D-2 receptor agonist apomorphine, although used clinically in the therapy of Parkinson's disease, has never been examined for any properties related to neuroprotection. In this paper, we examine the effects of 0.1-100 mu M apomorphine on ascorbate/iron-stimulated free radical processes in rat brain mitchondrial fraction. Lipid peroxidation as assayed by the thiobarbituric acid reaction can be completely inhibited by submicromolar concentrations of apomorphine (0.3 mu M with 2.5 mu M Fe2+ and 0.6 mu M with 5.0 mu M Fe2+), which proved to be more than twice as effective as desferrioxamine and twenty times as compared with dopamine. The inhibition of lipid peroxidation in mitochondria correlates with an increased rate of apomorphine oxidation. The formation of protein carbonyls, which is generally less sensitive to antioxidants, could be significantly reduced by apomorphine. In the model system we employed, apomorphine was more active than dopamine, desferrioxamine, or pergolide in preventing the formation of thiobarbituric reactive substances. The time course of the reaction suggests that apomorphine acts as a radical scavenger and that its iron chelating properties may not be of major importance. Since oxidative stress has been implicated in Parkinson's disease, the role of apomorphine as a neuroprotective is worthy of examination.