Document Detail


Modulation of streptonigrin cytotoxicity by nitroxide SOD mimics.
MedLine Citation:
PMID:  7835744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitroxides are cell-permeable, stable radicals that react readily with paramagnetic species such as transition metals or short-lived free radicals, though not generally with diamagnetic molecules. Nitroxides can undergo one-electron selective redox reactions and thereby potentially modify the activity of cytotoxic drugs. Streptonigrin (SN) toxicity requires bioreduction to yield the semiquinone radical, and the toxicity is reportedly mediated by transition metals and oxygen-derived reactive species via redox-cycling of the semiquinone intermediate. The present study shows that (1) nitroxides protected isolated DNA and also aerated or hypoxic bacterial cells from SN toxicity; (2) H2O2 potentiated the hypoxic cytotoxicity of the drug but inhibited the damage to aerated cells; (3) pretreatment of cells with H2O2 conferred some protection, but not when the drug alone was preexposed to H2O2; and (4) desferrioxamine and 2,2-dipyridyl, though neither diethylenetriamino pentaacetate, exogenous catalase, or superoxide dismutase, decreased SN-induced cell killing. The mechanisms by which nitroxides protect from SN toxicity involve both a selective radical-radical reaction with SN semiquinone and the reoxidation of reduced cellular transition metal ions. On the other hand, H2O2 appears to exert two opposing effects: (1) facilitation of cell killing by the Fenton reaction and (2) lowering the cellular level of reducing equivalents, thus inhibiting the bioreductive activation of SN.
Authors:
M C Krishna; R F Halevy; R Zhang; P L Gutierrez; A Samuni
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  17     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1995-02-24     Completed Date:  1995-02-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  379-88     Citation Subset:  IM    
Affiliation:
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
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MeSH Terms
Descriptor/Qualifier:
Aerobiosis
Anaerobiosis
Cyclic N-Oxides / pharmacology*
DNA Damage*
Electron Spin Resonance Spectroscopy
Escherichia coli / drug effects*,  growth & development
Free Radicals
Hydrogen Peroxide / toxicity
Hydroxyl Radical / analysis
Kinetics
Spin Labels
Streptonigrin / toxicity*
Superoxide Dismutase*
Superoxides / analysis
Chemical
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Free Radicals; 0/Spin Labels; 11062-77-4/Superoxides; 14691-88-4/tempamine; 3352-57-6/Hydroxyl Radical; 3930-19-6/Streptonigrin; 7722-84-1/Hydrogen Peroxide; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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