Reduced serum hydroxyl radical scavenging activity in erythropoietin therapy resistant renal anemia.
Relation between anemia resistant to recombinant human erythropoietin (rHuEPO) therapy and the oxidative stress in hemodialysis (HD) patients was investigated. Stable HD patients who had consistent hemoglobin concentrations on a constant dose of rHuEPO were studied. Patients were excluded if there were factors that might affect hemopoiesis or administration of antioxidant supplements. Patients were classified into three groups: High (9000 U/week), Low (1500-4500 U/week) and No rHuEPO group. Thiobarbituric acid reactive substances (TBARS) of sera and erythrocyte were examined. Serum superoxide and hydroxyl radical scavenging activities were measured using electron spin resonance. TBARS in the erythrocyte was higher in High rHuEPO group compared with No rHuEPO group, though the serum TBARS were similar. A diminution of serum hydroxyl radical scavenging activity was observed in High rHuEPO group. Hydroxyl radical signal intensity showed a strong correlation with the serum ferritin in High rHuEPO group, although ferritin concentrations were not different among the 3 groups. Superoxide scavenging activity showed no differences. These results indicate that increased lipid peroxidation in erythrocyte, raised by decreased serum hydroxyl radical scavenging activity, is one cause of rHuEPO resistant anemia. Serum ferritin may be involved in this hydroxyl radical production.
Hirayama
Aki
A
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. aki-hira@md.tsukuba.ac.jp
Nagase
Sohji
S
Gotoh
Michihiro
M
Ueda
Atsushi
A
Ishizu
Takashi
T
Yoh
Keigyou
K
Aoyagi
Kazumasa
K
Terao
Junji
J
Koyama
Akio
A
D000368:Aged; D000740:Anemia / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D004351:Drug Resistance; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005293:Ferritins / Q000097:blood; D016166:Free Radical Scavengers / Q000097:blood*; D006801:Humans; D017665:Hydroxyl Radical / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000150:complications*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013481:Superoxides / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016166:Free Radical Scavengers; D011994:Recombinant Proteins; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D004921:Erythropoietin; D017665:Hydroxyl Radical; D005293:Ferritins