Plasma protein-bound di-tyrosines as biomarkers of oxidative stress in end stage renal disease patients on maintenance haemodialysis

Graziano Colombo , Francesco Reggiani , David Cucchiari , Nicola M. Portinaro , Daniela Giustarini , Ranieri Rossi , Maria Lisa Garavaglia , Nicola Saino , Aldo Milzani , Salvatore Badalamenti , Isabella Dalle-Donne
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引用次数: 14

Abstract

Background

Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience enhanced oxidative stress and systemic inflammation, which are risk factors for cardiovascular disease, the most common cause of excess morbidity and mortality for these patients. Different pathways producing different types of oxidative stress occur in ESRD. The purpose of our study was to determine the effect of HD on plasma levels of protein-bound dityrosine (di-Tyr), a biomarker of protein oxidation.

Methods

Protein-bound di-Tyr formation was measured by size exclusion HPLC coupled to fluorescence detector. Clinical laboratory parameters were measured by standardized methods.

Results

In most ESRD patients, a single HD session decreased significantly the plasma protein-bound di-Tyr level, although the mean post-HD level remained significantly greater than the one in healthy people. Furthermore, pre-HD plasma protein-bound di-Tyr level was positively correlated with pre-HD serum creatinine and albumin concentrations. No significant correlation was found between plasma protein-bound di-Tyr level and serum concentration of C-reactive protein, a biomarker of systemic inflammation.

Conclusions

This study demonstrates that a single HD session does not increase, rather partially decreases, oxidative pathways producing di-Tyr in the haemodialyzed patient.

General significance

The choice of the most pertinent biomarkers of oxidative stress is critical for the development of novel treatments for ESRD. However, the relative importance of oxidative stress and inflammation in ESRD remains largely undetermined, and several questions concerning oxidative stress and inflammation remain poorly defined. These results could stimulate further studies on the use of plasma protein-bound di-Tyr as a long-lasting oxidative stress biomarker in ESRD.

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血浆蛋白结合二酪氨酸作为终末期肾病维持血液透析患者氧化应激的生物标志物
背景:接受血液透析(HD)的终末期肾病(ESRD)患者会经历氧化应激和全身性炎症的增强,这是心血管疾病的危险因素,也是这些患者发病率和死亡率过高的最常见原因。ESRD中产生不同类型氧化应激的途径不同。我们研究的目的是确定HD对血浆蛋白结合二酪氨酸(di-Tyr)水平的影响,二酪氨酸是一种蛋白质氧化的生物标志物。方法采用尺寸排除高效液相色谱法结合荧光检测器检测蛋白结合二酪氨酸的形成。采用标准化方法测定临床实验室参数。结果在大多数ESRD患者中,单次HD治疗显著降低血浆蛋白结合的di-Tyr水平,尽管HD后的平均水平仍显著高于健康人群。此外,hd前期血浆蛋白结合的di-Tyr水平与hd前期血清肌酐和白蛋白浓度呈正相关。血浆蛋白结合的di-Tyr水平与血清c反应蛋白(全身性炎症的生物标志物)浓度之间无显著相关性。结论:本研究表明,在血液透析患者中,单次HD治疗不会增加,反而会部分减少产生二tyr的氧化途径。选择最相关的氧化应激生物标志物对于开发ESRD的新治疗方法至关重要。然而,氧化应激和炎症在ESRD中的相对重要性在很大程度上仍未确定,有关氧化应激和炎症的几个问题仍未明确。这些结果可以刺激进一步研究血浆蛋白结合的二tyr作为ESRD中持久氧化应激生物标志物的使用。
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