Hydroxyl radical generation dependent on extracellular ascorbate in rat striatum, as determined by microdialysis
Hydroxyl radical generation dependent on extracellular ascorbate in rat striatum, as determined by microdialysis
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DOI：
10.1016/j.tox.2008.12.025
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发表时间：
2009-04-05
期刊：
影响因子：
4.5
通讯作者：
Endo, Takahiko
中科院分区：
文献类型：
--
作者：
Hara, Shuichi;Mizukami, Hajime;Endo, Takahiko
抗坏血酸（AA）是一种称为维生素C的抗氧化物质，以高浓度存在于大脑中，尽管AA本身全身给药后转移到大脑中是有限的。腹腔注射脱氢抗坏血酸（DHA）导致大鼠纹状体细胞外AA以剂量依赖性方式快速和进行性增加。DHA给药增加了水杨酸盐的2，3-和2，5-二羟基苯甲酸酯（2，3-和2，5-DHBA）形成，同时细胞外AA增加。纹状体内给予活性AA氧化酶（AAO），而不是失活的酶，完全抑制了DHA给药后2，3-和2，5-DHBA形成的增加。这些发现表明，细胞外AA可能刺激纹状体中羟基自由基（（中心点）OH）的产生。这得到了观察到的剂量依赖性（中心点）羟基生成后，纹状体内管理AA本身。此外，去铁胺，铁螯合剂，减少基础的2，3-和2，5-DHBA的形成和强烈，但不完全，抑制DHA诱导的2，3-和2，5-DHBA的形成增加。因此，增加细胞外AA可能作为一种促氧化剂，并刺激（中心点）与铁在大鼠纹状体中的OH的产生。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Ascorbate (AA), an antioxidant substance known as vitamin C, exists in the brain at a high concentration, although transfer into the brain after systemic administration of AA itself is limited. Intraperitoneal administration of dehydroascorbate (DHA) resulted in a rapid and progressive increase in extracellular AA in rat striatum in a dose-dependent manner. DHA administration increased 2,3- and 2,5-dihydroxybenzoate (2,3- and 2,5-DHBA) formation from salicylate in parallel with the increase in extracellular AA. Intrastriatal administration of active AA oxidase (AAO), but not the inactivated enzyme, completely suppressed the increase in 2,3- and 2,5-DHBA formation after the DHA administration. These findings suggest that extracellular AA might stimulate hydroxyl radical ((center dot)OH) generation in the striatum. This is supported by the observation of dose-dependent (center dot)OH generation upon intrastriatal administration of AA itself. In addition, deferoxamine, an iron chelator, decreased basal 2,3- and 2,5-DHBA formation and strongly, though not completely, suppressed the DHA-induced increase of 2,3- and 2,5-DHBA formation. Therefore, increased extracellular AA might function as a prooxidant and stimulate (center dot)OH generation in cooperation with iron in rat striatum. (C) 2009 Elsevier Ireland Ltd. All rights reserved.