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Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea

机译:羟基脲治疗镰状细胞性贫血患者中性粒细胞的细胞毒性和DNA损伤

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Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p0.0001), especially when treated for longer periods (20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.
机译:羟基脲(HU)是镰状细胞性贫血(SCA)预防并发症和改善患者生活质量的最重要进展。但是,HU治疗的某些方面仍不清楚,包括它们对其他血细胞(如中性粒细胞)的影响和潜在毒性。这项研究使用乳酸脱氢酶(LDH)和甲基噻唑四唑(MTT)的测量以及彗星试验来研究HU对SCA患者中性粒细胞DNA的细胞毒性和损伤指数(DI)。 ,在所治疗的患者组中观察到了细胞保护作用,并且没有毒性。与未接受治疗的患者相比,SS组(n = 20,女性13位,男性07,年龄18-69岁)和健康个体(AA)组用作对照组(n = 52,28位女性和24名男性,年龄在19-60岁之间),SSHU组(n = 21,11名女性和10名男性,年龄在19-63岁之间)显示LDH活性显着降低(p <0.001),并且LDH的百分比增加MTT检测发现有活力的细胞(p <0.001)。然而,与AA组(7.43±0.94U / A)和SS组(22.73±5.58 U / A)相比,SSHU组的DI值显着更高(49.57±6.0 U / A)(p <0.0001) ,特别是当治疗时间较长(> 20个月)时,表明尽管就细胞生存力而言具有细胞保护作用,但HU的使用仍可诱导中性粒细胞的DNA损伤。

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