Respective role of uraemic toxins and myeloperoxidase in the uraemic state
Respective role of uraemic toxins and myeloperoxidase in the uraemic state
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DOI：
10.1093/ndt/gfl007
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发表时间：
2006-06-01
影响因子：
6.1
通讯作者：
Witko-Sarsat, Veronique
中科院分区：
文献类型：
--
作者：
Capeillere-Blandin, Chantal;Gausson, Valerie;Witko-Sarsat, Veronique
背景。在血液透析（HD）患者中，高级氧化蛋白产物（AOPP）以前被归因于氧化的血浆蛋白，主要是由于髓过氧化物酶（MPO）活性增加所致。本研究的目的是评估慢性肾病（包括终末期肾病）过程中导致 AOPP 生成的机制，特别关注肾功能水平下降时血浆中 AOPP 和 MPO 的特征。方法。通过全血 NADPH 氧化酶和 MPO 活性评估吞噬细胞活化。在血浆中，通过 ELISA 定量 MPO 蛋白浓度，并通过分光光度法检测过氧化氢 (H2O2) 存在下苯酚和 4-氨基安替比林 (AAP) 的共氧化反应来测定催化活性。结果。在 HD 患者中，血浆 AOPP 浓度与中性粒细胞氧化活性相关。在对照受试者或透析前患者中没有发现这种关联，这表明在后者中，AOPP 的生成并非主要由活化的中性粒细胞释放的 MPO 引起。同样，HD 患者的血浆 AOPP 与血浆 MPO 蛋白浓度相关，但在对照受试者或透析前患者中则不然，这表明后者的 AOPP 并非主要由 MPO 活性引起。与 HD 患者或对照受试者相比，在没有 H2O2 的情况下，透析前患者中苯酚和 AAP 的共氧化程度更高，这一解释得到了支持。 MPO 的贡献在透析前患者和 HD 患者之间存在显着差异（2 +/- 5 vs 46 +/- 6%；P < 0.001）。结论。我们的观察表明，透析前患者中 AOPP 的产生主要是由不依赖 MPO 的氧化机制引起的。
Background. In haemodialysis (HD) patients, advanced oxidation protein products (AOPP) were previously ascribed to oxidized plasma proteins, resulting mainly from increased myeloperoxidase (MPO) activity. The aim of the present study was to assess the mechanisms leading to the generation of AOPP during the course of chronic kidney disease including end-stage renal disease, with particular focus on AOPP and MPO characterization in the plasma at decreasing levels of kidney function.Methods. Phagocyte activation was evaluated by whole blood NADPH oxidase and MPO activities. In plasma, MPO protein concentration was quantified by ELISA and catalytic activity assayed by the spectrophotometric detection of phenol and 4-aminoantipyrine (AAP) co-oxidation in the presence of hydrogen peroxide (H2O2).Results. In HD patients, plasma AOPP concentration was linked to neutrophil oxidative activity. Such an association was not found in control subjects or predialysis patients, suggesting that in the latter, AOPP generation did not mainly result from MPO released by activated neutrophils. Similarly, plasma AOPP correlated with plasma MPO protein concentration in HD patients, but not in control subjects or predialysis patients, suggesting that in the latter AOPP did not predominantly result from MPO activity. This interpretation was supported by the observation of a greater degree of co-oxidation of phenol and AAP in the absence of H2O2 in predialysis patients than in HD patients or control subjects. The contribution of MPO dramatically differed between predialysis and HD patients (2 +/- 5 vs 46 +/- 6%; P < 0.001).Conclusion. Our observations suggest that AOPP generation in predialysis patients mainly results from MPO-independent oxidation mechanisms.