The NADPH oxidase inhibitor apocynin (acetovanil.lone) induces oxidative stress
The NADPH oxidase inhibitor apocynin (acetovanil.lone) induces oxidative stress
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DOI：
10.1016/j.taap.2005.07.011
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发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Ghigo, Dario
中科院分区：
文献类型：
--
作者：
Riganti, Chiara;Costamagna, Costanzo;Ghigo, Dario
夹竹桃素（乙酰香草酮）常被用作NADPH氧化酶的特异性抑制剂。在N11胶质细胞中，罗布麻素以剂量依赖的方式诱导丙二醛水平（脂质过氧化指数）和乳酸脱氢酶释放（细胞毒性作用指数）的显著增加。Apocynin还能显著提高H2O2浓度，降低细胞内谷胱甘肽/谷胱甘肽二硫比，并伴有谷胱甘肽和谷胱甘肽二硫的外排增加。夹竹桃苷诱导戊糖磷酸途径和三羧酸循环的激活，当谷胱甘肽和夹竹桃苷共同孵育细胞时，这两个途径被阻断。谷胱甘肽抑制了夹竹桃素诱导的丙二醛生成和乳酸脱氢酶渗漏的增加。在无细胞系统中，罗布麻碱也有氧化作用：事实上，在水溶液中，罗布麻碱能更快地氧化硫代谷胱甘肽和二硫代苏糖醇，并引起活性氧的产生，主要是超氧阴离子。我们的研究结果表明，罗布麻素本身可以诱导N11细胞和其他细胞类型的氧化应激并发挥细胞毒性作用，在体外和体内实验模型中，罗布麻素的一些作用应谨慎解释。(c) 2005爱思唯尔公司版权所有。
Apocynin (acetovanillone) is often used as a specific inhibitor of NADPH oxidase. In N11 glial cells, apocynin induced, in a dose-dependent way, a significant increase of both malonyldialdehyde level (index of lipid peroxidation) and lactate dehydrogenase release (index of a cytotoxic effect). Apocynin evoked also, in a significant way, an increase Of H2O2 concentration and a decrease of the intracellular glutathione/glutathione disulfide ratio, accompanied by augmented efflux of glutathione and glutathione disulfide. Apocynin induced the activation of both pentose phosphate pathway and tricarboxylic acid cycle, which was blocked when the cells were incubated with glutathione together with apocynin. The cell incubation with glutathione prevented also the apocynin-induced increase of malonyldialdehyde generation and lactate dehydrogenase leakage. Apocynin exerted an oxidant effect also in a cell-free system: indeed, in aqueous solution, it evoked a faster oxidation Of the thiols glutathione and dithiothreitol, and elicited the generation of reactive oxygen species, mainly superoxide anions. Our results suggest that apocynin per se can induce an oxidative stress and exert a cytotoxic effect in N11 cells and other cell types, and that some effects of apocynin in in vitro and in vivo experimental models should be interpreted with caution. (c) 2005 Elsevier Inc. All rights reserved.