Müller Christoph, Eisenbrand Gerhard, Gradinger Martina, Rath Thomas, Albert Franz Werner, Vienken Jörg, Singh Rajinder, Farmer Peter B, Stockis Jean-Pierre, Janzowski Christine
Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, Technical University of Kaiserslautern, Kaiserslautern, Germany.
Free Radic Res. 2004 Oct;38(10):1093-100. doi: 10.1080/10715760400011452.
Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde-deoxyguanosine-adducts (M1dG) with an immunoslot blot technique. HD-patients (n=21) showed a significant increase of total DNA damage (p<10(-12)), compared to controls (n=12). In a subset of patients and controls, GSSG levels and M1dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally increased (p<0.005). Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion.
接受血液透析（HD）的尿毒症患者被认为面临动脉粥样硬化和癌症的风险升高。这部分归因于氧化应激增加。在这项初步研究中，将HD患者血液中的氧化细胞损伤与对照组进行了比较：通过彗星试验（有和没有FPG）、动力学光度测定法和血浆丙二醛（MDA）的HPLC定量分别监测总DNA损伤（基本和特定的氧化DNA损伤）、谷胱甘肽水平（总谷胱甘肽和氧化型谷胱甘肽）的调节以及脂质过氧化。在一些样本中，用免疫印迹技术分析白细胞中的丙二醛 - 脱氧鸟苷加合物（M1dG）。与对照组（n = 12）相比，HD患者（n = 21）的总DNA损伤显著增加（p < 10^(-12)）。然而，在一部分患者和对照组中，氧化型谷胱甘肽水平和M1dG仅略有增加，而总谷胱甘肽和MDA水平没有差异。在一项初步研究中，对9名患者进行了测试，他们依次使用三种膜类型进行四周的透析，以测试不同低通量HD膜的影响。除了患者的个体因素外，透析器膜对氧化应激有显著影响。发现聚砜膜和维生素E涂层纤维素膜的总DNA损伤几乎相同，而醋酸纤维素膜则有轻微但显著的增加（p < 0.001）。在HD期间接受铁输注的患者中，MDA形成（n = 11）和总DNA损伤（n = 10）进一步增加（p < 0.005）。我们的结果表明，与健康志愿者相比，HD患者的氧化损伤增加。发现透析器膜类型和铁输注有显著影响。
