Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt; Department of Clinical Chemistry, Maadi Armed Forces Hospital, Cairo, Egypt.
Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt.
J Adv Res. 2016 May;7(3):348-58. doi: 10.1016/j.jare.2016.02.004. Epub 2016 Feb 23.
Inflammation and oxidative stress are two faces of one coin in end stage renal disease patients (ESRD) on maintenance hemodialysis. Their interconnection induces anemia complicated with erythropoietin hyporesponsiveness. The biochemical bases behind the resistance to erythropoietin therapy with frequent hemoglobinemia, oxidative stress and iron status have not been fully understood. Here two equal groups (40 patients each) of responders and non-responders to recombinant human erythropoietin therapy (higher than 300 IU/kg/wk of epoetin) were investigated. Hematological and biochemical analyses of collected blood and serum samples were performed along with serum electrophoretic protein footprinting. The leukocytic DNA fragmentation was used to evaluate the degree of oxidative insult. The good responders showed lower erythrocyte malondialdehyde (E-MDA) level and less DNA fragmentation of circulating leukocytes than poor responders with elevated hemoglobin, albumin, A/G ratio, total iron, and ferritin levels. Contrariwise, lower erythrocyte superoxide dismutase (E-SOD) and catalase activities in EPO poor responder group were noticed. Neither other serum constituents nor electrophoretic protein pattern showed any difference between the two groups. There were higher levels of inflammatory markers, interleukin-6 (IL6) and C-reactive protein (CRP) in EPO poor responder than good responder. The negative correlations between Hb and both IL6 and CRP levels in the present data remotely indicate a positive correlation between inflammatory markers and severity of anemia. A direct correlation between Hb and antioxidant enzymes (E-SOD and catalase) was noticed, while inverse correlation with E-MDA was recorded. The study proved that oral supplementation of vitamin C to ESRD patients might mitigate the previously elevated serum MDA level in these patients.
在接受维持性血液透析的终末期肾病（ESRD）患者中，炎症和氧化应激是同一硬币的两面。它们的相互作用导致贫血合并红细胞生成素反应低下。频繁的血红蛋白血症、氧化应激和铁状态导致对红细胞生成素治疗产生抵抗的生化基础尚未完全理解。在这里，我们调查了对重组人红细胞生成素治疗（高于 300 IU/kg/wk 的促红素）有反应和无反应的两组（每组 40 例）患者。对采集的血液和血清样本进行了血液学和生化分析，并进行了血清电泳蛋白足迹分析。白细胞 DNA 片段化用于评估氧化损伤程度。与血红蛋白、白蛋白、A/G 比值、总铁和铁蛋白水平升高的不良反应者相比，良好反应者的红细胞丙二醛（E-MDA）水平较低，循环白细胞的 DNA 片段化程度较低。相反，在 EPO 反应不良者中，红细胞超氧化物歧化酶（E-SOD）和过氧化氢酶活性较低。两组之间的其他血清成分或电泳蛋白图谱均无差异。EPO 反应不良者的炎症标志物白细胞介素-6（IL6）和 C 反应蛋白（CRP）水平较高。本研究数据中 Hb 与 IL6 和 CRP 水平之间的负相关表明，炎症标志物与贫血严重程度之间存在正相关。Hb 与抗氧化酶（E-SOD 和过氧化氢酶）之间存在直接相关性，而与 E-MDA 呈负相关。该研究证明，向 ESRD 患者口服补充维生素 C 可能会减轻这些患者先前升高的血清 MDA 水平。
