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J Am Soc Nephrol 11:539-549, 2000
© 2000 American Society of Nephrology

Vitamin E Attenuates Oxidative Stress Induced by Intravenous Iron in Patients on Hemodialysis

JOHANNES M. ROOB*, GHOLAMALI KHOSCHSORUR{dagger}, ANDREAS TIRAN{ddagger}, JÖRG H. HORINA*, HERWIG HOLZER* and BRIGITTE M. WINKLHOFER-ROOB§

* Division of Clinical Nephrology and Hemodialysis, Department of Internal Medicine, Karl-Franzens University of Graz, Austria.
{dagger} Department of Laboratory Medicine I, Karl-Franzens University of Graz, Austria.
{ddagger} Department of Laboratory Medicine II, Karl-Franzens University of Graz, Austria.
§ Institute of Biochemistry, Karl-Franzens University of Graz, Austria.

Correspondence to Dr. Brigitte M. Winklhofer-Roob, Institute of Biochemistry, Karl-Franzens University, Schubertstrasse 1, A-8010 Graz, Austria. Phone: +43 316 380 5490; Fax: +43 316 380 9857; E-mail: brigitte.winklhoferoob{at}kfunigraz.ac.at

Abstract. Intravenous iron application to anemic patients on hemodialysis leads to an "oversaturation" of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(II) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-{alpha}-tocopheryl acetate taken 6 h before the hemodialysis session. Blood was drawn before and 30, 60, 90, 135, and 180 min after the start of the iron infusion, and areas under the curve (AUC0-180 min) of ratios of plasma malondialdehyde (MDA) to cholesterol and plasma total peroxides to cholesterol (two markers of lipid peroxidation) were determined as the outcome variables. At baseline of the session without vitamin E supplementation, plasma {alpha}-tocopherol concentrations (27.6 ± 1.8 µmol/L) and ratios of {alpha}-tocopherol to cholesterol (5.88 ± 1.09 mmol/mol) were normal, plasma MDA concentrations were above normal (1.20 ± 0.28 µmol/L), and bleomycin-detectable iron (BDI), indicating the presence of redox-active iron, was not detectable. Upon iron infusion, BDI and MDA concentrations increased significantly (P < 0.001). BDI concentrations explained the increase over baseline in MDA concentrations (MDA = 1.29 + 0.075 x BDI). Vitamin E supplementation, leading to a 68% increase in plasma {alpha}-tocopherol concentrations, significantly reduced the AUC0-180 min of MDA to cholesterol (P = 0.004) and peroxides to cholesterol (P = 0.002). These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron. Given that intravenous iron is applied repeatedly to patients on hemodialysis, this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term.




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