Hydroxyurea‐mediated release of nitric oxide in myeloproliferative neoplasms patients: Effects on platelet–leukocyte interaction

Gumiero, Daniela; Gennaro, Leonardo Di; Nicolazzi, Maria Anna; Landolfi, Raffaele

doi:10.1002/jcph.548

Cited by 3 publications

(4 citation statements)

References 19 publications

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“…Hydroxyurea, also known as hydroxycarbamide, is an oral chemotherapeutic drug used in the treatment of sickle cell disease and several cancers [71,72] . In this context, Chemiluminescence analysis confirms that horseradish peroxidase catalyses the formation of NO• through the peroxidation of hydroxyurea [73] . In addition, gas chromatographic analysis of the reaction headspace confirmed the formation of 20 % N 2 O after 1 hour in a solution of hydroxyurea, hydrogen peroxide, and HRP.…”

Section: Endogenous Hno Generation Pathwaysmentioning

confidence: 89%

“…[71,72] In this context, Chemiluminescence analysis confirms that horseradish peroxidase catalyses the formation of NO * through the peroxidation of hydroxyurea. [73] In addition, gas chromatographic analysis of the reaction headspace confirmed the formation of 20 % N 2 O after 1 hour in a solution of hydroxyurea, hydrogen peroxide, and HRP. Furthermore, gas infrared spectroscopy of the reaction mixture confirmed the formation of N 2 O by showing characteristic peaks at 2223 and 1284 cm À 1 .…”

Section: Generation Of Hno By Hydroxylamine Oxidationmentioning

confidence: 91%

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Update on Endogenous HNO Production: An Exploration of Unanswered Questions and Challenges

Vargas,

Doctorovich,

Suarez

2024

Eur J Inorg Chem

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This review consolidates the evidence supporting endogenous HNO generation through enzymatic and non‐enzymatic pathways, emphasizing advancements in real‐time HNO sensing within living systems. Azanone (nitroxyl, HNO) is the one‐electron‐reduced congener of nitric oxide (NO•) and shares various biological actions. HNO exhibits unique properties, including positive inotropic and lusitropic effects, along with resistance to scavenging by reactive oxygen species (ROS), particularly superoxide. Research on HNO has intensified over the last two decades, focusing on its reactivity and the prospect of endogenous formation due to its potential significance. The high reactivity of HNO arises from reactions with biologically relevant species such as oxygen, NO•, and thiols, as well as self‐dimerization. Detecting and quantifying HNO has posed challenges, initially relying on nitrous oxide (N2O) detection, a byproduct of dimerization. Recent advancements, including fluorescent probes and a specific electrochemical nanomolar‐level sensor, have facilitated direct detection, enhancing understanding of HNO reactivity and formation.

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Section: Endogenous Hno Generation Pathwaysmentioning

confidence: 89%

Section: Generation Of Hno By Hydroxylamine Oxidationmentioning

confidence: 91%

Update on Endogenous HNO Production: An Exploration of Unanswered Questions and Challenges

Vargas,

Doctorovich,

Suarez

2024

Eur J Inorg Chem

View full text Add to dashboard Cite

show abstract

“…In addition to providing cytoreduction, hydroxyurea reduces neutrophil activity, decreases expression of endothelial adhesion molecules, and induces nitric oxide generation. [29][30][31][32][33] The findings of Alvarez-Larran et al 28 seem to mirror the concept of short-remitters by Cortelazzo et al, 13 wherein a short-lived or lack of platelet response represents higher-risk disease.…”

mentioning

confidence: 80%

What’s in a Number? Examining the Prognostic and Predictive Importance of Platelet Count in Patients With Essential Thrombocythemia

Kuykendall

Komrokji

2020

Journal of the National Comprehensive Cancer Network

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Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by clonal overproduction of platelets and an increased risk of thrombohemorrhagic complications. Patients are risk stratified by driver mutation, age, and thrombotic history and treated to reduce the risk of thrombotic and hemorrhagic events. The significance of platelet number as a risk factor or treatment goal is unclear. Despite the preponderance of data failing to demonstrate an association, there exists a pervasive belief that higher platelet counts correlate with an increased thrombotic risk. In fact, the association between thrombocytosis and bleeding is more clearly supported. Variability in regional consensus guidelines contributes to the uncertainty. This article reviews the data that shed light on the importance of platelet count in patients with ET.

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“… 9 In addition to reducing the incidence of hospitalization and acute pain in SCD, hydroxyurea reduces the occurrence of acute chest syndrome and may provide an alternative to chronic transfusion therapy in some subjects at risk of stroke, 125 , 126 indicating benefits on the hemostatic and thromboinflammatory mechanisms that contribute to these complications. However, curiously, while an association of hydroxy urea therapy with reduced levels of hypercoagulability biomarkers has been reported in SCD, 127 together with reductions in platelet-fibrinogen binding, leukocyte TF expression and complement activation, 38 , 105 , 128 the effects of hydroxyurea on platelet-leukocyte aggregate formation 129 and on the circulating concentrations of some platelet-derived pro-inflammatory molecules are less clear. 10 ,108 128…”

Section: Perspectivesmentioning

confidence: 99%

Thromboinflammatory mechanisms in sickle cell disease - challenging the hemostatic balance

Conran

Paula

2020

haematol

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Sickle cell disease (SCD) is an inherited hemoglobinopathy that is caused by the presence of abnormal hemoglobin S (HbS) in red blood cells, leading to alterations in red cell properties and shape, as the result of HbS dexoygenation and subsequent polymerization. SCD pathophysiology is characterized by chronic inflammatory processes, triggered by hemolytic and vaso-occlusive events, which lead to the varied complications, organ damage and elevated mortality seen in individuals with the disease. In association with activation of the endothelium and leukocytes, hemostatic alterations and thrombotic events are well-documented in SCD. Here we discuss the role for inflammatory pathways in modulating coagulation and inducing platelet activation in SCD, due to tissue factor activation, adhesion molecule expression, inflammatory mediator production and the induction of innate immune responses, amongst other mechanisms. Thromboinflammatory pathways may play a significant role in some of the major complications of SCD, such as stroke, venous thromboembolism and possibly acute chest syndrome, besides exacerbating the chronic inflammation and cellular interactions that trigger vaso-occlusion, ischemia-reperfusion processes, and eventually organ damage.

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Hydroxyurea‐mediated release of nitric oxide in myeloproliferative neoplasms patients: Effects on platelet–leukocyte interaction

Cited by 3 publications

References 19 publications

Update on Endogenous HNO Production: An Exploration of Unanswered Questions and Challenges

Update on Endogenous HNO Production: An Exploration of Unanswered Questions and Challenges

What’s in a Number? Examining the Prognostic and Predictive Importance of Platelet Count in Patients With Essential Thrombocythemia

Thromboinflammatory mechanisms in sickle cell disease - challenging the hemostatic balance

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