Document Detail


The reaction of cell-free oxyhemoglobin with nitrite under physiologically relevant conditions: Implications for nitrite-based therapies.
MedLine Citation:
PMID:  19010434     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitric oxide (NO*) participates in the regulation of a wide array of biological processes and its deficit contributes to the severity of many diseases. Recently, a role of NO deficiency that occurs as a result of intravascular hemolysis and increases in levels of cell-free hemoglobin in the pathway of chronic anemic pathologies has been suggested. Experimental evidence for deoxyhemoglobin-catalyzed reduction of nitrite to NO* leads to the possibility of nitrite infusion-based therapies to correct NO* deficits. However, the presence of plasma hemoglobin also raises the possibility of deleterious free radical-mediated oxidative damage from the reaction between nitrite and oxyhemoglobin in the vasculature. We show that the conditions required for the reaction between nitrite and oxyhemoglobin to exhibit free radical-mediated autocatalytic kinetics are highly unlikely to occur in the plasma compartment, even during extensive hemolysis and with pharmacological nitrite doses. Although the presence of haptoglobin enhances the rate of the reaction between nitrite and oxyhemoglobin, common plasma antioxidants-ascorbate and urate, as well as catalase-prevent autocatalysis. Our findings suggest that pharmacological doses of nitrite are unlikely to cause free radical or ferrylhemoglobin formation in plasma originating from the reaction of nitrite with cell-free oxyhemoglobin in vivo.
Authors:
Barbora Piknova; Agnes Keszler; Neil Hogg; Alan N Schechter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2008-11-05
Journal Detail:
Title:  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society     Volume:  20     ISSN:  1089-8611     ISO Abbreviation:  Nitric Oxide     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-03-30     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9709307     Medline TA:  Nitric Oxide     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Ascorbic Acid / metabolism
Catalase / metabolism
Electron Spin Resonance Spectroscopy
Free Radicals / metabolism
Haptoglobins / metabolism
Hemoglobins / metabolism
Humans
Methemoglobin / metabolism
Nitrites / chemistry,  metabolism*
Oxyhemoglobins / chemistry,  metabolism*
Plasma / metabolism*
Regression Analysis
Uric Acid / metabolism
Grant Support
ID/Acronym/Agency:
EB001980/EB/NIBIB NIH HHS; GM55792/GM/NIGMS NIH HHS; P41 EB001980/EB/NIBIB NIH HHS; P41 EB001980-28/EB/NIBIB NIH HHS; P41 EB001980-29/EB/NIBIB NIH HHS; P41 EB001980-30/EB/NIBIB NIH HHS; P41 EB001980-31/EB/NIBIB NIH HHS; P41 EB001980-32/EB/NIBIB NIH HHS; R01 GM055792-07/GM/NIGMS NIH HHS; R01 GM055792-08/GM/NIGMS NIH HHS; R01 GM055792-09/GM/NIGMS NIH HHS; R01 GM055792-10A2/GM/NIGMS NIH HHS; R01 GM055792-11/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Free Radicals; 0/Haptoglobins; 0/Hemoglobins; 0/Nitrites; 0/Oxyhemoglobins; 0/ferrylhemoglobin; 268B43MJ25/Uric Acid; 9008-37-1/Methemoglobin; EC 1.11.1.6/Catalase; PQ6CK8PD0R/Ascorbic Acid
Comments/Corrections

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