Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship
العنوان: | Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship |
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المؤلفون: | Romélia Pinheiro Gonçalves Lemes, Luzia Kalyne Almeida Moreira Leal, Alano Martins Pedrosa |
المصدر: | Hematology, Transfusion and Cell Therapy, Vol 43, Iss 4, Pp 468-475 (2021) Hematology, Transfusion and Cell Therapy Hematology, Transfusion and Cell Therapy, Volume: 43, Issue: 4, Pages: 468-475, Published: 29 NOV 2021 |
بيانات النشر: | Elsevier, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Neutrophils, Cytotoxicity, 030204 cardiovascular system & hematology, Pharmacology, medicine.disease_cause, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, medicine, Immunology and Allergy, Hydroxyurea, Dose–effect, Diseases of the blood and blood-forming organs, chemistry.chemical_classification, Inflammation, biology, business.industry, Glutathione peroxidase, Hematology, chemistry, Oxidative stress, Myeloperoxidase, Toxicity, biology.protein, Sickle cell anemia, Trypan blue, Tumor necrosis factor alpha, Original Article, RC633-647.5, business, 030215 immunology |
الوصف: | 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. |
وصف الملف: | text/html |
اللغة: | English |
تدمد: | 2531-1379 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5eadebd89ea53b6a6a4167044df85e3Test http://www.sciencedirect.com/science/article/pii/S2531137920302820Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....e5eadebd89ea53b6a6a4167044df85e3 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 25311379 |
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