Hara Shuichi, Mizukami Hajime, Kuriiwa Fumi, Endo Takahiko
Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Toxicology. 2009 Apr 5;258(1):10-6. doi: 10.1016/j.tox.2008.12.025. Epub 2009 Jan 9.
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 (OH) generation in the striatum. This is supported by the observation of dose-dependent 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 OH generation in cooperation with iron in rat striatum.
抗坏血酸盐（AA），即一种被称为维生素C的抗氧化物质，在大脑中以高浓度存在，尽管全身给予AA本身后其进入大脑的量有限。腹腔注射脱氢抗坏血酸盐（DHA）导致大鼠纹状体细胞外AA迅速且呈剂量依赖性地逐渐增加。给予DHA后，水杨酸生成2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸（2,3 - 和2,5 - DHBA）的量与细胞外AA的增加平行。纹状体内注射活性抗坏血酸氧化酶（AAO）而非失活的酶，完全抑制了给予DHA后2,3 - 和2,5 - DHBA生成的增加。这些发现表明细胞外AA可能会刺激纹状体中羟自由基（OH）的产生。这一观点得到了纹状体内注射AA本身时OH产生呈剂量依赖性这一观察结果的支持。此外，铁螯合剂去铁胺减少了基础状态下2,3 - 和2,5 - DHBA的生成，并强烈（但未完全）抑制了DHA诱导的2,3 - 和2,5 - DHBA生成的增加。因此，细胞外AA增加可能作为一种促氧化剂，并与铁协同刺激大鼠纹状体中OH的产生。
