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初治原发性血小板增多症的氧化状态:单中心的一项初步研究

Oxidative status in treatment-naïve essential thrombocythemia: a pilot study in a single center.

作者信息

Iurlo Alessandra, De Giuseppe Rachele, Sciumè Mariarita, Cattaneo Daniele, Fermo Elisa, De Vita Claudia, Consonni Dario, Maiavacca Rita, Bamonti Fabrizia, Gianelli Umberto, Cortelezzi Agostino

机构信息

Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, University of Milan, Milano, Italy.

Oncohematology Unit of the Elderly, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milano, Italy.

出版信息

Hematol Oncol. 2017 Sep;35(3):335-340. doi: 10.1002/hon.2264. Epub 2015 Oct 6.

Abstract

Oxidative stress (OS), due to pro-oxidant species [reactive oxygen species (ROS)] excess not counterbalanced by endogenous antioxidant molecules [e.g., reduced glutathione (GSH)], is involved in the pathogenesis of human cancers, but few data are available on essential thrombocythemia (ET). This study aims to investigate OS in ET off-therapy patients. Thirty ET treatment-naïve patients were compared with 26 age-matched and gender-matched controls. Serum ROS, urinary 8-hydroxydeoxyguanosine, full blood GSH levels, and reduced/oxidized GSH ratio (GSH/GSSG) were measured. Data were adjusted for gender, age, JAK2 mutational status, smoking, dyslipidemia, or hypercholesterolemia requiring drug therapy, antiplatelet therapy, treatment with acetylsalicylic acid, high-sensitive C-reactive protein levels, and absolute monocyte count. ROS and GSH levels were increased in both patients and controls. Patients showed increased GSSG (p = 0.05), reduced GSH/GSSG ratio (p = 0.08), and similar 8-hydroxydeoxyguanosine levels when compared with controls. No differences in OS parameters were found between JAK2-positive and JAK2-negative patients. Confounding factors did not modify the results. Our study suggests an OS condition in a cohort of treatment-naïve ET patients, not associated with JAK2 mutational status or with chronic inflammation situation. GSH/GSSG ratio, altered in ET patients because of increased GSSG levels, showed the presence of higher GSH levels in ET than controls as a possible compensatory mechanism of an excess of pro-oxidant production. Copyright © 2015 John Wiley & Sons, Ltd.

摘要

氧化应激(OS)是由于促氧化物质[活性氧(ROS)]过量而未被内源性抗氧化分子[如还原型谷胱甘肽(GSH)]抵消所致,它参与人类癌症的发病机制,但关于原发性血小板增多症(ET)的数据较少。本研究旨在调查未经治疗的ET患者的氧化应激情况。将30例未经治疗的ET患者与26例年龄和性别匹配的对照组进行比较。测量血清ROS、尿8-羟基脱氧鸟苷、全血GSH水平以及还原型/氧化型GSH比值(GSH/GSSG)。对数据进行了性别、年龄、JAK2突变状态、吸烟、血脂异常或需要药物治疗的高胆固醇血症、抗血小板治疗、阿司匹林治疗、高敏C反应蛋白水平和绝对单核细胞计数的校正。患者和对照组的ROS和GSH水平均升高。与对照组相比,患者的GSSG升高(p = 0.05),GSH/GSSG比值降低(p = 0.08),8-羟基脱氧鸟苷水平相似。JAK2阳性和JAK2阴性患者之间的氧化应激参数没有差异。混杂因素未改变结果。我们的研究表明,一组未经治疗的ET患者存在氧化应激状态,这与JAK2突变状态或慢性炎症情况无关。由于GSSG水平升高,ET患者的GSH/GSSG比值发生改变,表明ET患者的GSH水平高于对照组,这可能是促氧化剂产生过多的一种代偿机制。版权所有© 2015 John Wiley & Sons, Ltd.

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