The effect of erythropoietin on the cellular defence mechanism of red blood cells in children with chronic renal failure

Abstract

The glutathione redox system, haemoglobin (Hb) oxidation, the activity of antioxidant enzymes and the lipid peroxidation product malonyl dialdehyde (MDA) were studied in red blood cells (RBCs) during administration of recombinant human erythropoietin (rhEPO) over 12 weeks in ten children maintained on haemodialysis. A rapid increase in the reticulocyte count was accompanied by a slower rise in total Hb concentration. The mean level of oxidized glutathione (GSSG) increased from 13.2 +/- 5.3 nmol/g Hb to 56.7 +/- 15.8 nmol/g Hb 4 weeks after the start of rhEPO (P < 0.001), followed by a fall to the basal value. Reduced glutathione (GSH) levels showed a smaller though constant elevation during rhEPO therapy (P < 0.001). Before rhEPO treatment, incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in GSH concentration compared with controls (P < 0.001), which became more pronounced in the first few weeks of rhEPO therapy (P < 0.001). In addition, the percentage of Hb derivatives (metHb and haemichrome) increased in the first 4 weeks of rhEPO therapy (P < 0.001). Although there was no significant difference between the values obtained preEPO and during EPO treatment, MDA levels were continuously higher and superoxide dismutase, catalase and glutathione peroxidase concentrations were lower than in the controls (P < 0.001). These results are compatible with oxidative damage to the RBCs in the early period of rhEPO therapy in children with end-stage renal failure. The GSH-GSSG system, as an important cellular defence mechanism of the RBCs, appears to be severely affected.