Intravenous Iron Exacerbates Oxidative DNA Damage in Peripheral Blood Lymphocytes in Chronic Hemodialysis Patients

Patients undergoing maintenance hemodialysis have elevated markers of oxidative stress, but the reasons for this are not fully understood. Intravenous administration of iron, which many of these patients receive, may provoke the generation of bioactive iron, which enhances oxidative stress and lipid peroxidation. In this study, 110 hemodialysis patients were randomly assigned to five groups that were administered single intravenous doses of iron sucrose, ranging from 20 to 500 mg. A time- and dosage-dependent rise in lymphocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in lymphocyte DNA, a marker of oxidative DNA damage, with a significant increase at 2 h after intravenous iron of > or = 200 mg (P < 0.05). Four weeks later, patients were randomly assigned to weekly iron sucrose (100 mg of elemental iron) or saline for 12 wk, and 89 patients completed the study. Mean lymphocyte 8-OHdG content was significantly higher in patients receiving intravenous iron compared with control subjects (P < 0.05), especially in those with ferritin levels > 500 microg/L. In addition, flow cytometric techniques revealed increased production of reactive oxygen species in lymphocytes among those treated with intravenous iron. Treatment with intravenous iron but not saline was also associated with decreased plasma ascorbate and alpha-tocopherol levels and increased oxidized glutathione/reduced glutathione ratio (P < 0.05). In summary, intravenous iron sucrose provokes oxidative damage to peripheral blood lymphocyte DNA in hemodialysis patients, especially among those with high levels of ferritin.