Prooxidant effects of ascorbate in rat brain slices

Ascorbate is a web-known reducing agent, but it can generate oxidative pote ntial under appropriate condition. In rat cerebral cortex homogenate, I mM ascorbate decreased thiobarbituric acid-reactive substances (TBARS) content to 86% +/- 4% of control values, confirming that ascorbate is a reducing a gent. However, ascorbate increased TEARS, in a dose-related manner, in slic es prepared from cerebral cortex. Ferrous ion (Fe2+) had little effect on a scorbate-induced lipid oxidation in cortical slices, and EDTA did not have an influence on the ascorbate-induced oxidative action, Conversely, ascorba te plus Fe2+ elevated TEARS content to more than threefold over ascorbate a lone in tissue homogenates. In summary, ascorbate is a reducing agent in th e brain tissue homogenate but has an oxidizing effect in brain slices. A hy pothesis is proposed to explain the oxidative effects of ascorbate in corti cal slices, wherein extracellular ascorbate is oxidized to dehydroascorbate , which is rapidly carried into the cells via a glucose transporter (GLUT). The dehydroascorbate in cytosol is then reduced back to ascorbate, and, du ring the reduction process, cellular components are oxidized. (C) 1999 Wile y-Liss, Inc.