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Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes
Author(s) -
Kim Eun Joo,
Park Yong Gou,
Baik Eun Joo,
Jung Se Jung,
Won Ran,
Nahm Taik Sang,
Lee Bae Hwan
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20384
Subject(s) - dehydroascorbic acid , glutathione , programmed cell death , ascorbic acid , chemistry , reactive oxygen species , pentose phosphate pathway , antioxidant , glutathione reductase , glutathione peroxidase , biochemistry , hydrogen peroxide , oxidative stress , apoptosis , vitamin c , metabolism , enzyme , glycolysis , food science
Ascorbic acid (AA) is a well‐known antioxidant. It also has pro‐oxidant effects, however, in the presence of free transition metals. Because of the pro‐oxidant effects of AA, dehydroascorbic acid (DHA), an oxidized form of AA, has been used as a substitute for AA. DHA has been shown recently to have a protective effect in an experimental stroke model. This study was carried out to determine if DHA has different effects from AA on hydrogen peroxide (H 2 O 2 )‐induced oxidative cell death in primary astrocytes. DHA was found to prevent cell death and reverse mitochondrial dysfunction after exposure to H 2 O 2 . DHA significantly increased the glutathione peroxidase (GPx) and glutathione reductase (GR) activities 1 hr after H 2 O 2 exposure. Moreover, DHA not only reversed the decrease in the glutathione (GSH) levels, but also significantly enhanced it by stimulating the pentose phosphate pathway (PPP) 15 hr after H 2 O 2 exposure. DHA also reduced production of reactive oxygen species (ROS) after H 2 O 2 exposure. In contrast, AA accelerated H 2 O 2 ‐induced cell death. To determine if the pro‐oxidant effect of AA is related to iron, the effect of AA on cell death was examined using an iron chelator, desferrioxamine. Even though co‐pretreatment with AA and desferrioxamine could abrogate the aggravating effects of AA on H 2 O 2 ‐induced cell death at early stages, it could not prevent H 2 O 2 ‐induced cell death over a 24‐hr period. These results suggest that DHA has distinct effects from AA and prevent H 2 O 2 ‐induced cell death by increasing the GSH levels mediated by the GPx and GR activities and PPP. © 2005 Wiley‐Liss, Inc.