The reaction of cell-free oxyhemoglobin with nitrite under physiologically relevant conditions: Implications for nitrite-based therapies. Nitric Oxide 2009 Mar;20(2):88-94
Date
11/18/2008Pubmed ID
19010434Pubmed Central ID
PMC2698998DOI
10.1016/j.niox.2008.10.005Scopus ID
2-s2.0-59049096495 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Piknova B, Keszler A, Hogg N, Schechter ANAuthors
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinAgnes Keszler PhD Research Scientist I in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Ascorbic AcidCatalase
Electron Spin Resonance Spectroscopy
Free Radicals
Haptoglobins
Hemoglobins
Humans
Methemoglobin
Nitrites
Oxyhemoglobins
Plasma
Regression Analysis
Uric Acid
