Hydroxyurea has the capacity to induce damage to human erythrocytes which can be modified by radical scavengers

Malec, J; Przybyszewski, Waldemar M.; Grabarczyk, Małgorzata; Sitarska, E

doi:10.1016/0006-291x(84)91292-0

Cited by 29 publications

(13 citation statements)

References 12 publications

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“…Hydroxyurea also induces both hemoglobin denaturation and oxidative damage within red blood cells [97][98][99][100]. Further EPR examination of the reaction of oxyhemoglobin and hydroxyurea reveals the formation of three other paramagnetic species in addition to methemoglobin [101].…”

Section: Reactions With Heme Proteinsmentioning

confidence: 94%

The Nitric Oxide Producing Reactions of Hydroxyurea

King¹

2003

CMC

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Hydroxyurea is used to treat a variety of cancers and sickle cell disease. Despite this widespread use, a complete mechanistic understanding of the beneficial actions of this compound remains to be understood. Hydroxyurea inhibits ribonucleotide reductase and increases the levels of fetal hemoglobin, which explains a portion of the effects of this drug. Administration of hydroxyurea to patients results in a significant increase in levels of iron nitrosyl hemoglobin, nitrite and nitrate suggesting the in vivo metabolism of hydroxyurea to nitric oxide. Formation of nitric oxide from hydroxyurea may explain a portion of the observed effects of hydroxyurea treatment. At the present, the mechanism or mechanisms of nitric oxide release, the identity of the in vivo oxidant and the site of metabolism remain to be identified. Chemical oxidation of hydroxyurea produces nitric oxide and nitroxyl, the one-electron reduced form of nitric oxide. These oxidative pathways generally proceed through the nitroxide radical (2) or C-nitrosoformamide (3). Biological oxidants, including both iron and copper containing enzymes and proteins, also convert hydroxyurea to nitric oxide or its decomposition products in vitro and these reactions also occur through these intermediates. A number of other reactions of hydroxyurea including the reaction with ribonucleotide reductase and irradiation demonstrate the potential to release nitric oxide and should be further investigated. Gaining an understanding of the metabolism of hydroxyurea to nitric oxide will provide valuable information towards the treatment of these disorders and may lead to the development of better therapeutic agents.

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Section: Reactions With Heme Proteinsmentioning

confidence: 94%

The Nitric Oxide Producing Reactions of Hydroxyurea

King¹

2003

CMC

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“…While it is now widely accepted that Ep-independent ('abnormal') clones proliferate in PV, it has yet to be established to what extent the erythrocytes deriving from these clones exhibit consistent changes in their characteristics. But when studying an occasional group of PV patients, we might get a wide range of results, since the erythrocyte populations come from a spectrum of progenitors of differing maturation, unique to each patient (17), and these paients are also under various therapies, which in itself can cause changes in the erythrocytic properties (3,18). Even so, we could demonstrate, in the present communication, some properties which were significantly different in erythrocytes of PV patients compared to normals.…”

Section: Discussionmentioning

confidence: 99%

Some characteristics of circulating erythrocytes in polycythaemia vera: Common features with normal young and foetal red blood cells

Streichman

Avdi

Joffe

et al. 1986

Scandinavian Journal of Haematology

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Although it is well established that in polycythaemia vera (PV) both ‘normal’ and ‘abnormal’ erythroid progenitors proliferate, it is less known to what extent the circulating erythrocytes express normal characteristics. We found reduced erythrocyte densities, decreased MCHC, and increased lipid content. These properties, together with increased sialic acid, seem to explain the extremely low sedimentation rate and decreased deformability of polycythaemic blood samples. Other characteristics were high activity of glycolytic enzymes, increased in vitro production of lactate, and a concomitant decline in ATP and 2,3‐diphosphoglycerate. Some of these properties have been described in foetal erythrocytes and are features of normal young red cells. However, they seem to represent true features of PV and not a consequence of younger cell populations. The similarity between mature erythrocytes in PV and in foetal life supports the possibility that the proliferation process in this disease has a mechanism in common with foetal erythropoiesis.

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“…compounds are highly toxic compounds formed as primary products in the N-oxidation by cytochrome P-450 (2). It has been recently reported that NH,OH and its derivatives react avidly with hemoglobin (3)(4)(5). Reactive free radicals are recognized as highly toxic intermediates in this reaction affecting the integrity of hemoproteins and erythrocytes when generated from intraerythrocytic hemoglobin (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Reactive free radicals are recognized as highly toxic intermediates in this reaction affecting the integrity of hemoproteins and erythrocytes when generated from intraerythrocytic hemoglobin (6)(7)(8). Hemolysis, oxidation of oxyhemoglobin to methemoglobin and the formation of highly reactive ferry1 heme species, as well as blood cell dysfunction were reported to occur (4)(5)(6)(7)(8). Experimental evidence for the existence of the toxic intermediates mentioned above came from electron spin resonance (ESR) and chemiluminescence measurements.…”

Section: Introductionmentioning

confidence: 99%

Light Emission Resulting from Hydroxylamine‐Induced Singlet Oxygen Formation of Oxidizing LDL Particles

Liu

Stolze

Dadak

et al. 1997

Photochem & Photobiology

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Oxidation of low-density lipoprotein (LDL) by low amounts of cupric ions resulted in the formation of singlet oxygen (1O2, 1 delta g) when hydroxylamine (NH2OH) was added. Direct evidence on this excited species came from partial spectral resolution of the emitted light in the red spectral region (634 nm and 703 nm), which can be attributed to the dimol decay of singlet oxygen. Additional evidence for the existence of singlet oxygen came from the enhancing effect of deuterium oxide buffer (D2O) on chemiluminescence intensity and the quenching effect of sodium azide. A linear correlation between NH2OH-dependent chemiluminescence intensity and the amount of diene conjugates (DC) formed in this reaction was observed. Removal of adventitious transition metals by adequate chelators prevented chemiluminescence in this system; NH2OH was also found to efficiently decrease metabolites of lipid peroxidation (LPO). Our findings are consistent with a sequence of reactions in which NH2OH first converts transition metals to their reduced state, thereby stimulating the formation of alkoxy- and peroxyradicals. Peroxyradicals decompose in a bimolecular Russel reaction to hydroxyl compounds and singlet oxygen while the majority of alkoxy radicals are eliminated by a secondary reaction with NH2OH. Identical effects were observed when reducing antioxidants such as ascorbic acid or trolox C were used instead of hydroxylamine.

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Hydroxyurea has the capacity to induce damage to human erythrocytes which can be modified by radical scavengers

Cited by 29 publications

References 12 publications

The Nitric Oxide Producing Reactions of Hydroxyurea

The Nitric Oxide Producing Reactions of Hydroxyurea

Some characteristics of circulating erythrocytes in polycythaemia vera: Common features with normal young and foetal red blood cells

Light Emission Resulting from Hydroxylamine‐Induced Singlet Oxygen Formation of Oxidizing LDL Particles

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