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NADH-generating substrates reduce peroxyl radical toxicity in RL-34 cells.
MedLine Citation:
PMID:  19950075     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
There is general agreement that oxidative stress may induce apoptotic and necrotic cell death. Recently it has been shown that NADH can be considered an important antioxidant as it reacts with peroxyl and alkoxyl radicals under in vitro conditions. Therefore, in the present study we hypothesized that an increase in intracellular NADH using specific substrates will protect RL-34 cells against cytotoxicity of 2'-azobis (2-amidinopropane) dihydrochloride (AAPH), which is a peroxyl radical generating compound. Cells treated for 24 hours with 6.0 mM AAPH were severely damaged: mitochondria were vacuolated, and the level of free radicals significantly increased. Both apoptotic and necrotic cells were detected (11.1% and 11.4%, respectively) even after 5 hours of treatment. Pretreatment of the cells with substrates which increase the intracellular level of NADH, such as lactate, beta-hydroxybutyrate, and ethanol, distinctly inhibited AAPH-induced reactive oxygen species (ROS) formation and cell death. On the other hand, acetoacetate (AcA), which decrease the intracellular level of NADH, had opposite effects. Interestingly, NADH-generating substrates augment, while AcA reduced superoxide radical formation induced by AAPH. These results may suggest that although NADH generating substrates may exert some deleterious effects within a cell by inducing reductive stress, they diminish alkoxyl or peroxyl radical cytotoxicity. The protection is associated with a decrease in ROS formation measured by dichlorofluorescein, but with an increase in superoxide radical formation.
Authors:
J Antosiewicz; J H Spodnik; M Teranishi; A Herman-Antosiewicz; Ch Kurono; T Soji; M Woźniak; A Borkowska; T Wakabayashi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Folia morphologica     Volume:  68     ISSN:  0015-5659     ISO Abbreviation:  Folia Morphol. (Warsz)     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-12-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374620     Medline TA:  Folia Morphol (Warsz)     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  247-55     Citation Subset:  IM    
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