Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings
Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings
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DOI：
10.1111/jnc.12082
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Sitges, Maria
中科院分区：
文献类型：
--
作者：
Herrera-Mundo, Nieves;Sitges, Maria
长春新碱是一种神经保护药物，对神经系统症状和脑血管疾病产生有益的影响。3-硝基丙酸（3-NPA）是一种不可逆地抑制琥珀酸脱氢酶的毒素，琥珀酸脱氢酶是在复合物II的电子传递链中起作用的线粒体酶。在以前的研究中，在纹状体分离的神经末梢（突触体），我们发现，长春新碱减少多巴胺（DA）的费用，其主要代谢产物3，4-二羟基苯乙酸（DOPAC），和3-NPA增加DA，活性氧（ROS），DA-醌产品的形成，并减少DOPAC。因此，在这项研究中，长春新碱对3-NPA诱导的DA，ROS，脂质过氧化反应，DA-醌产品的形成在纹状体突触体的增加的可能影响进行了研究，并与抗氧化剂α-生育酚的影响进行了比较。结果表明，25 μ M长春新碱和50 μ M α-生育酚均抑制3-NPA诱导的DA增加。长春新碱作为α-生育酚，也抑制3-NPA诱导的ROS增加（通过DCF荧光判断）、脂质过氧化（通过TBA-RS形成判断）和DA-醌产物形成（通过氮蓝四唑还原法判断）。由于除了3-NPA对复合物II的抑制作用外，3-NPA还增加了DA-氧化产物，而DA-氧化产物又可以抑制呼吸链的其他位点，因此长春新碱和α-生育酚产生的DA下降可能对它们免受氧化损伤的保护作用有重要贡献，特别是在富含DA的结构中。
Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant alpha-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 mu M vinpocetine and 50 mu M alpha-tocopherol. Vinpocetine, as alpha-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and alpha-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures.