Melatonin prevents oxidative stress resulting from iron and erythropoietinadministration

Intravenous iron (Fe) and recombinant human erythropoietin (rHuEPO) are rou tine treatments in the management of anemia In patients with chronic renal failure. We investigated the oxidative stress acutely induced by these ther apies and whether pretreatment with oral melatonin (MEL) would have a benef icial effect. Nine patients (four women) were studied within 1 month of ent ering a chronic hemodialysis program in the interdialytic period. Plasma ma londialdehyde (MDA), red blood cell glutathione (GSH), and catalase (CAT) a ctivity were measured In blood samples obtained before (baseline) and 1, 3, and 24 hours after the administration of Fe (100 mg of Fe saccharate intra venously over 1 hour) or rHuEPO (4,000 U intravenously). One hour before th ese treatments, patients were administered a single oral dose of MEL (0.3 m g/kg) or placebo. Each patient was studied on four occasions, corresponding to studies performed using either placebo or MEL in association with intra venous Fe and rHuEPO administration. Baseline data showed increased oxidati ve stress in patients with end-stage renal failure. Increments in oxidative stress Induced by Fe were more pronounced at the end of the administration : MDA, baseline, 0.74 +/- 0.09 nmol/mL; 1 hour, 1.50 +/- 0.28 nmol/mL (P < 0.001); GSH, baseline, 2.51 +/- 0.34 nmol/mg of hemoglobin (Hb); 1 hour, 1. 66 +/- 0.01 nmol/mg Hb (P < 0.001); and CAT activity, baseline, 27.0 +/- 5. 7 kappa /mg Hb; 1 hour, 23.3 +/- 4.2 kappa /mg Hb (P < 0.001). rHuEPO-Induc ed increments in oxidative stress were more pronounced (P < 0.001) at 3 hou rs (MDA, 1.24 +/- 0.34 nmol/mL; GSH, 1.52 +/- 0.23 nmol/mg Hb; CAT activity , 18.0 +/- 3.1 kappa /mg Hb). MEL administration prevented the changes indu ced by Fe and rHuEPO and had no adverse side effects. These studies show th at intravenous Fe and rHuEPO in doses commonly used to treat anemia in chro nic hemodialysis patients acutely generate significant oxidative stress. Or al MEL prevents such oxidative stress and may be of clinical use. (C) 2001 by the National Kidney Foundation, Inc.