Pro-oxidative synergic bactericidal effect of NO: kinetics and inhibition by nitroxides

Yadav,R, Samuni,Y, Abramson,A, Zeltser,R, Casap,N, Kabiraj,TK, L Banach,M and Samuni,U 2014, Pro-oxidative synergic bactericidal effect of NO: kinetics and inhibition by nitroxides, Free radical biology and medicine, vol. 67, pp. 248-254, doi: 10.1016/j.freeradbiomed.2013.10.012.

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Title Pro-oxidative synergic bactericidal effect of NO: kinetics and inhibition by nitroxides
Author(s) Yadav,R
L Banach,M
Journal name Free radical biology and medicine
Volume number 67
Start page 248
End page 254
Publisher Elsevier
Place of publication Philadelphia, PA
Publication date 2014-02
ISSN 1873-4596
Keyword(s) Free radicals
Hydrogen peroxide
Microbial pathogens
Nitric oxide
Oxidative stress
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Endocrinology & Metabolism
Summary NO plays diverse roles in physiological and pathological processes, occasionally resulting in opposing effects, particularly in cells subjected to oxidative stress. NO mostly protects eukaryotes against oxidative injury, but was demonstrated to kill prokaryotes synergistically with H2O2. This could be a promising therapeutic avenue. However, recent conflicting findings were reported describing dramatic protective activity of NO. The previous studies of NO effects on prokaryotes applied a transient oxidative stress while arbitrarily checking the residual bacterial viability after 30 or 60min and ignoring the process kinetics. If NO-induced synergy and the oxidative stress are time-dependent, the elucidation of the cell killing kinetics is essential, particularly for survival curves exhibiting a "shoulder" sometimes reflecting sublethal damage as in the linear-quadratic survival models. We studied the kinetics of NO synergic effects on H2O2-induced killing of microbial pathogens. A synergic pro-oxidative activity toward gram-negative and gram-positive cells is demonstrated even at sub-μM/min flux of NO. For certain strains, the synergic effect progressively increased with the duration of cell exposure, and the linear-quadratic survival model best fit the observed survival data. In contrast to the failure of SOD to affect the bactericidal process, nitroxide SOD mimics abrogated the pro-oxidative synergy of NO/H2O2. These cell-permeative antioxidants, which hardly react with diamagnetic species and react neither with NO nor with H2O2, can detoxify redox-active transition metals and catalytically remove intracellular superoxide and nitrogen-derived reactive species such as (•)NO2 or peroxynitrite. The possible mechanism underlying the bactericidal NO synergy under oxidative stress and the potential therapeutic gain are discussed.
Language eng
DOI 10.1016/j.freeradbiomed.2013.10.012
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Elsevier
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Document type: Journal Article
Collection: School of Medicine
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