Proposed Mechanism of Nitrite-Induced Methemoglobinemia

Titov, V. Yu.; Petrenko, Yu. M.

doi:10.1007/s10541-005-0139-7

Cited by 65 publications

(47 citation statements)

References 26 publications

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“…1B. These spectra include those of metHb, oxyHb, and ferrylHb, as well as metHb-NO 2 Ϫ that may form due to the weak association of nitrite with metHb. The results of the regression analysis for the data in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…1 To whom correspondence should be addressed: 8701 Watertown Plank Rd., Milwaukee,; E-mail: nhogg@mcw.edu. 2 The abbreviations used are: deoxyHb, deoxyhemoglobin; oxyHb, oxyhemoglobin; metHb, methemoglobin; ferrylHb, ferrylhemoglobin; met-NO 2 Ϫ , methemoglobin nitrite; MLR, multilinear regression analysis; PB, phosphate buffer; CPTIO, 2-(carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide. …”

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confidence: 99%

“…Elevated levels of nitrite in blood can trigger the oxidation of hemoglobin, leading to methemoglobinemia (1,2). The mechanism of nitrite-dependent oxidation of deoxyhemoglobin (deoxyHb) 2 under anaerobic conditions, and its physiological potential in hypoxic vasodilation has recently been established (3)(4)(5).…”

mentioning

confidence: 99%

“…The mechanism of nitrite-dependent oxidation of deoxyhemoglobin (deoxyHb) 2 under anaerobic conditions, and its physiological potential in hypoxic vasodilation has recently been established (3)(4)(5). However, the mechanism of reaction between oxyhemoglobin (oxyHb) and nitrite has not yet been fully elucidated.…”

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confidence: 99%

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The Reaction between Nitrite and Oxyhemoglobin

Keszler

Piknová

Schechter

et al. 2008

Journal of Biological Chemistry

103

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The nitrite anion (NO 2 ؊ ) has recently received much attention as an endogenous nitric oxide source that has the potential to be supplemented for therapeutic benefit. One major mechanism of nitrite reduction is the direct reaction between this anion and the ferrous heme group of deoxygenated hemoglobin. However, the reaction of nitrite with oxyhemoglobin (oxyHb) is well established and generates nitrate and methemoglobin (metHb). Several mechanisms have been proposed that involve the intermediacy of protein-free radicals, ferryl heme, nitrogen dioxide (NO 2 ), and hydrogen peroxide (H 2 O 2 ) in an autocatalytic free radical chain reaction, which could potentially limit the usefulness of nitrite therapy. In this study we show that none of the previously published mechanisms is sufficient to fully explain the kinetics of the reaction of nitrite with oxyHb. Based on experimental data and kinetic simulation, we have modified previous models for this reaction mechanism and show that the new model proposed here is consistent with experimental data. The important feature of this model is that, whereas previously both H 2 O 2 and NO 2 were thought to be integral to both the initiation and propagation steps, H 2 O 2 now only plays a role as an initiator species, and NO 2 only plays a role as an autocatalytic propagatory species. The consequences of uncoupling the roles of H 2 O 2 and NO 2 in the reaction mechanism for the in vivo reactivity of nitrite are discussed.Elevated levels of nitrite in blood can trigger the oxidation of hemoglobin, leading to methemoglobinemia (1, 2). The mechanism of nitrite-dependent oxidation of deoxyhemoglobin (deoxyHb) 2 under anaerobic conditions, and its physiological potential in hypoxic vasodilation has recently been established (3-5). However, the mechanism of reaction between oxyhemoglobin (oxyHb) and nitrite has not yet been fully elucidated. Existing mechanistic approaches, starting with the earliest observations of Gamgee in 1868 (6), were recently reviewed (7). The end products of the reaction are methemoglobin (metHb) and nitrate. The kinetics of this reaction, when nitrite is in excess, are complex and exhibit an initial slow phase (often referred to as the lag phase) that accelerates into a rapid phase (referred to as the propagation phase) of oxidation. This reaction profile has been modeled as an autocatalytic, free radical chain reaction. The chain carrier radical and the autocatalytic steps have been variously hypothesized. Doyle et al. (8) found that hydrogen peroxide (H 2 O 2 ) accelerated oxyHb decay, whereas both catalase and superoxide dismutase elongated the half-time of the reaction. Based on these observations they suggested a mechanism according to which H 2 O 2 and superoxide played crucial roles. At the same time, Kosaka et al. (9) observed that catalase could extend the slow phase, but observed no effect of superoxide dismutase. In addition, they detected a transient protein free radical by EPR spectroscopy, and proposed a model with the intermediacy of H 2...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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The Reaction between Nitrite and Oxyhemoglobin

Keszler

Piknová

Schechter

et al. 2008

Journal of Biological Chemistry

103

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“…9,10 So, when nitrites are present at high concentration in blood, they react with the iron(III) of the hemoglobin, forming met hemoglobin, which has no oxygen carrying ability; this disease is called blue baby syndrome. 11,12 Therefore, development a credible and sensitive sensor to detect nitrite in food, drinking water and environmental samples has received continued attention over the past 10 years. Several methods have been developed for nitrite determination, including spectrophotometry, 13,14 chemiluminescence, 15 chromatography, 16,17 capillary electrophoresis 18 and electrochemical methods.…”

Section: Introductionmentioning

confidence: 99%

A Simple and Efficient Electrochemical Sensor for Electrocatalytic Reduction of Nitrite Based on Poly(4‐aminoacetanilide) Film Using Carbon Paste Electrode

Ojani

Raoof

Rahemi

2011

J Chinese Chemical Soc

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In this study, the electrochemical reduction of nitrite was investigated on poly(4-aminoacetanilide) (PPAA) forming by cyclic voltammetry at the surface of carbon paste electrode. The electrochemical properties of the modified electrode have been studied by cyclic voltammetry and double potential step chronoamperometry. Results showed that in the optimum condition (pH = 0.00) the reduction of nitrite occurred at a potential about 667 mV more positive than that unmodified carbon paste electrode. This amount of electrocatalytic ability is high compared with other electrocatalysts. Using a chronoamperometric method, the catalytic rate constant (k) was calculated 8.4 × 10 4 cm 3 mol -1 s -1 . Also, the electrocatalytic reduction peak currents was found to be linear with the nitrite concentration in the ranges of 5 × 10 -4 M to 2.5 × 10 -2 M and 2 × 10 -5 M to 7 × 10 -3 M with detection limits (2s) were determined as 4.5 × 10 -4 M and 1 × 10 -5 M by cyclic voltammetry (CV) and hydrodynamic amperometry methods respectively. Recovery experiments exhibit the satisfactory results.

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Methemoglobin—It's not just blue: A concise review

Umbreit¹

2006

American J Hematol

329

280

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Hemoglobin has functions besides carrying oxygen to the tissues, and regulates vascular tone and inflammation via a redox couple with methemoglobin. Hemoglobin has iron in the reduced valance Fe(II) and methemoglobin has iron in the oxidized valance Fe (III), with a free energy capable of producing water from oxygen. In generating methemoglobin the couple functions as a nitrite reductase. The degree of oxidation of hemoglobin senses the oxygen level in the blood and uses its ability to produce nitric oxide from nitrite to control vascular tone, increasing blood flood when the proportion of oxygenated hemoglobin falls. Additional cardiovascular damage is produced by methemoglobin mediated oxidation of light density lipoproteins, accelerating arteriosclerosis. In addition, the release of heme from methemoglobin is an important factor in inflammation. These physiologic functions are paralleled by the well-described role in the oxidation of various drugs resulting in methemoglobinemia. Am. J. Hematol. 82:134-144, 2007. V V C 2006 Wiley-Liss, Inc.

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Proposed Mechanism of Nitrite-Induced Methemoglobinemia

Cited by 65 publications

References 26 publications

The Reaction between Nitrite and Oxyhemoglobin

The Reaction between Nitrite and Oxyhemoglobin

A Simple and Efficient Electrochemical Sensor for Electrocatalytic Reduction of Nitrite Based on Poly(4‐aminoacetanilide) Film Using Carbon Paste Electrode

Methemoglobin—It's not just blue: A concise review

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