Articles

Article

Original

Exp Neurobiol 2008; 17(1): 25-31

Published online June 30, 2008

© The Korean Society for Brain and Neural Sciences

Effects of Ascorbic and Dehydroascorbic Acids on Apoptotic Cell Death in Hippocampal Slice Culture

Eun Jin Kim1, Ran Won2, Kyung Hee Lee1, Un Jeng Kim1, Insop Shim3, Hye-Jung Lee4, Bae Hwan Lee1*

1Department of Physiology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea, 2Department of Biomedical Laboratory Science, Division of Health Science, Dongseo University, Busan, Korea, 3Department of Integrative Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea, 4Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2228-1711, FAX: 82-2-393-0203
e-mail: bhlee@yuhs.ac

Abstract

Ascorbic acid (AA) and dehydroascorbic acid (DHA) are known to have protective effects in experimental central nerve system disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effect of AA and DHA on kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures (OHSC). Protective effects of AA and DHA on KA-induced cell death were evaluated by analyzing caspase-3. In addition, to determine if the prooxidant effect of AA is related to iron, the effect of AA on cell death was examined using desferrioxamine (DFO), an iron chelator. After 12h-KA treatment, significant delayed neuronal death was detected in CA3 region, but not in CA1. The AA (500ՌM) and DHA (100 and 500ՌM) pretreatments significantly prevented cell death by inhibiting caspase-3 activation in CA3 region. In the concentration of 1,000ՌM, however, AA pretreatment might have prooxidant effect, but AA-induced oxidative reaction is mainly not related to transition metal ions. These data showed that the pretreatments of intermediate-dose AA and DHA protected KA-induced neuronal damage in OHSCs and co-pretreatment of AA and DFO did not affect cell death except for a few cases. These data suggest that both AA and DHA pretreatment have antioxidant or prooxidant effect depending on doses treated on KA-induced neuronal injury and the possible prooxidant effect of AA may not depend on the Fenton reaction.

Keywords: ascorbic acid, dehydroascorbic acid, kainic acid, organotypic hippocampal slice culture, caspase-3