Clinical relevance of guanine-derived urinary biomarkers of oxidative stress, determined by LC-MS/MS.

Clinical relevance of guanine-derived urinary biomarkers of oxidative stress, determined by LC-MS/MS.
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通过液相色谱-串联质谱法(LC-MS/MS)测定的鸟嘌呤衍生的尿液氧化应激生物标志物的临床相关性。

DOI:
10.1016/j.redox.2018.11.016
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发表时间:
2019-01
期刊:
影响因子:
11.4
通讯作者:
Hu CW
Hu CW
中科院分区:
生物学1区
文献类型:
--
作者:
Shih YM;Cooke MS;Pan CH;Chao MR;Hu CW

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建立了一种可靠、快速的液相色谱-串联质谱法同时测定尿液中3种氧化核酸损伤产物8-氧鸟嘌呤(8-oxoGua)、8-氧-7,8-二氢-2 ' -脱氧鸟嘌呤(8-oxodGuo)和8-氧-7,8-二氢鸟嘌呤(8-oxoGuo)。我们应用这种方法来评估各种尿液检查程序对氧化核酸产物尿浓度的影响。我们的结果表明,在分析之前,冷冻尿液样本必须加热(即37 °C)以重新溶解任何沉淀物。我们发现,通常的处理方法,如室温解冻或用去离子水稀释,不能从沉淀中完全释放氧化的核酸产物,并导致显著的低估(8-oxoGua高达~ 100%,8-oxodGuo和8-oxoGuo均为~ 86%)。通过这种方法,我们进一步评估和比较了三种氧化核酸产物以及丙二醛(MDA,脂质过氧化产物)在体内生物监测氧化应激的能力。我们从低到高测量了315份氧化应激负荷受试者的尿液样本,包括健康受试者、慢性阻塞性肺疾病(COPD)患者和机械通气(MV)患者。结果显示,与健康对照组相比,MV和COPD患者尿中8-oxoGua、8-oxodGuo和8-oxoGuo水平均显著升高(P < 0.001),但MDA水平较低。受试者工作特征曲线分析显示,尿8-oxoGuo是氧化应激最敏感的生物标志物,曲线下面积(AUC)为0.91,其次是8-oxodGuo (AUC: 0.80)和8-oxoGua (AUC: 0.76)。有趣的是,AUC为0.34的MDA无法将患者与健康对照区分开。新出现的证据表明,尿液8-氧过含量的测量具有潜在的临床应用价值,在较小程度上,8-氧过含量的测量得到了我们研究结果的有力支持。
A reliable and fast liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of three oxidized nucleic acid damage products in urine, 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). We applied this method to assess the effect of various urine workup procedures on the urinary concentrations of the oxidized nucleic acid products. Our results showed that frozen urine samples must be warmed (i.e., to 37 °C) to re-dissolve any precipitates prior to analysis. We showed that common workup procedures, such as thawing at room temperature or dilution with deionized water, are not capable of releasing fully the oxidized nucleic acid products from the precipitates, and result in significant underestimation (up to ~ 100% for 8-oxoGua, ~ 86% for both 8-oxodGuo and 8-oxoGuo). With this method, we further assessed and compared the ability of the three oxidized nucleic acid products, as well as malondialdehyde (MDA, a product of lipid peroxidation), to biomonitor oxidative stress in vivo. We measured a total of 315 urine samples from subjects with burdens of oxidative stress from low to high, including healthy subjects, patients with chronic obstructive pulmonary disease (COPD), and patients on mechanical ventilation (MV). The results showed that both the MV and COPD patients had significantly higher urinary levels of 8-oxoGua, 8-oxodGuo, and 8-oxoGuo (P < 0.001), but lower MDA levels, compared to healthy controls. Receiver operating characteristic curve analysis revealed that urinary 8-oxoGuo is the most sensitive biomarker for oxidative stress with area under the curve (AUC) of 0.91, followed by 8-oxodGuo (AUC: 0.80) and 8-oxoGua (AUC: 0.76). Interestingly, MDA with AUC of 0.34 failed to discriminate the patients from healthy controls. Emerging evidence suggests a potential clinical utility for the measurement of urinary 8-oxoGuo, and to a lesser extent 8-oxodGuo, which is strongly supported by our findings.
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发表时间: 2005-04-01
影响因子: 3.7
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