Hydroxyl radical generation dependent on extracellular ascorbate in rat striatum, as determined by microdialysis

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.