Prooxidant effects of ascorbate in rat brain slices.
Ascorbate is a well-known reducing agent, but it can generate oxidative potential under appropriate condition. In rat cerebral cortex homogenate, 1 mM ascorbate decreased thiobarbituric acid-reactive substances (TBARS) content to 86% +/- 4% of control values, confirming that ascorbate is a reducing agent. However, ascorbate increased TBARS, in a dose-related manner, in slices prepared from cerebral cortex. Ferrous ion (Fe2+) had little effect on ascorbate-induced lipid oxidation in cortical slices, and EDTA did not have an influence on the ascorbate-induced oxidative action. Conversely, ascorbate plus Fe2+ elevated TBARS content to more than threefold over ascorbate alone in tissue homogenates. In summary, ascorbate is a reducing agent in the brain tissue homogenate but has an oxidizing effect in brain slices. A hypothesis is proposed to explain the oxidative effects of ascorbate in cortical 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, during the reduction process, cellular components are oxidized.
Song
J H
JH
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Shin
S H
SH
Ross
G M
GM
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D009004:Monosaccharide Transport Proteins; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D001205:Ascorbic Acid; D000077191:Wortmannin