Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alano Martins Pedrosa, Luzia Kalyne A.M. Leal, Romélia Pinheiro G. Lemes
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Sickle cell anemia Neutrophils Hydroxyurea Inflammation Oxidative stress Cytotoxicity Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/c923064b0797471aa27a538ff3a97fb9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c923064b0797471aa27a538ff3a97fb9
record_format	dspace
spelling	oai:doaj.org-article:c923064b0797471aa27a538ff3a97fb92021-11-04T04:37:20ZEffects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship2531-137910.1016/j.htct.2020.07.011https://doaj.org/article/c923064b0797471aa27a538ff3a97fb92021-10-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2531137920302820https://doaj.org/toc/2531-1379Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18–69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5–2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5–2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.Alano Martins PedrosaLuzia Kalyne A.M. LealRomélia Pinheiro G. LemesElsevierarticleSickle cell anemiaNeutrophilsHydroxyureaInflammationOxidative stressCytotoxicityDiseases of the blood and blood-forming organsRC633-647.5ENHematology, Transfusion and Cell Therapy, Vol 43, Iss 4, Pp 468-475 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Sickle cell anemia Neutrophils Hydroxyurea Inflammation Oxidative stress Cytotoxicity Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	Sickle cell anemia Neutrophils Hydroxyurea Inflammation Oxidative stress Cytotoxicity Diseases of the blood and blood-forming organs RC633-647.5 Alano Martins Pedrosa Luzia Kalyne A.M. Leal Romélia Pinheiro G. Lemes Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
description	Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18–69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5–2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5–2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.
format	article
author	Alano Martins Pedrosa Luzia Kalyne A.M. Leal Romélia Pinheiro G. Lemes
author_facet	Alano Martins Pedrosa Luzia Kalyne A.M. Leal Romélia Pinheiro G. Lemes
author_sort	Alano Martins Pedrosa
title	Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
title_short	Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
title_full	Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
title_fullStr	Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
title_full_unstemmed	Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
title_sort	effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c923064b0797471aa27a538ff3a97fb9
work_keys_str_mv	AT alanomartinspedrosa effectsofhydroxyureaoncytotoxicityinflammationandoxidativestressmarkersinneutrophilsofpatientswithsicklecellanemiadoseeffectrelationship AT luziakalyneamleal effectsofhydroxyureaoncytotoxicityinflammationandoxidativestressmarkersinneutrophilsofpatientswithsicklecellanemiadoseeffectrelationship AT romeliapinheiroglemes effectsofhydroxyureaoncytotoxicityinflammationandoxidativestressmarkersinneutrophilsofpatientswithsicklecellanemiadoseeffectrelationship
_version_	1718445300342849536

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

Ejemplares similares