Effect of intravenous vitamin C on cytokine activation and oxidative stress in end-stage renal disease patients receiving intravenous iron sucrose.
Reticuloendothelial blockade in hemodialysis patients prevents optimal intravenous (IV) iron utilization. Vitamin C has emerged as a potential therapy to improve anemia treatment by enhancing iron mobilization. However, Vitamin C can act as a pro-oxidant in the presence of iron. This was a prospective, open-label, crossover study. Thirteen patients with end-stage renal disease on hemodialysis and four healthy controls were assigned to receive 100 mg of IV iron sucrose (IS) or 100 mg of IV IS co-administered with 300 mg of IV Vitamin C (IS + C) in random sequence. Serum samples for IL-1, IL-6, TNF-α and IL-10 and non-transferrin bound iron were obtained at baseline, 45 min and 105 min post study medication administration. Peripheral blood mononuclear cells were isolated at the same time points and stained with fluorescent probes to identify intracellular reactive oxygen species and mitochondrial membrane potential (Δψm) by flow cytometry. Lipid peroxidation was assessed by plasma F2-isoprosatane concentration. Both IS and IS + C were associated with increased plasma F2-isoprostanes concentrations post-infusion. Maximal plasma F2-isoprostane concentrations after IS + C were significantly elevated from baseline (234 ± 0.04 vs. 0.198 ± 0.028 ng/mL, p = 0.02). After IS + C, IL-1, IL-6, IL-10, and TNF-alpha were significantly elevated compared to baseline. After IS alone only IL-6 was noted to be elevated. Intracellular production of H(2)O(2) and loss of mitochondrial membrane potential (Δψm) was observed after IS while IS + C was associated with increased O                            (2)                                      (·-)                          production. Both IS and IS + C induced serum cytokine activation accompanied by lipid peroxidation, however, IS + C induced higher plasma concentrations of F2-isoprostanes, IL-1, IL-10, and TNF-α post-infusion. Long-term safety studies of IV iron co-administered with Vitamin C are warranted.
Department of VA, Veterans Health Administration, Office of Research and Development, VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, 2401 Centre Avenue SE, Albuquerque, NM 87106, USA. todd.conner@va.gov
Todd A
TA
Conner
Charles
C
McQuade
Jonathan
J
Olp
Amy Barton
AB
Pai
D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage*; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D049490:Systems Biology
D016207:Cytokines; D028441:F2-Isoprostanes; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D000077605:Ferric Oxide, Saccharated; D001205:Ascorbic Acid; D005937:Glucaric Acid