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      The Effect of Intravenous Iron on Oxidative Stress in Hemodialysis Patients at Various Levels of Vitamin C

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          Abstract

          Background/Aims: Vitamin C levels decrease during hemodialysis (HD), which deteriorates antioxidant defense. Vitamin C may also act pro-oxidatively, via reduction in Fe(III). We sought to determine whether intravenous iron (Fe<sub>iv</sub>)-induced oxidative stress differs in HD patients with low and physiological vitamin C levels and whether intravenous vitamin C (C<sub>iv</sub>) administration during HD would change the response to Fe<sub>iv</sub>. Patients and Methods: Twenty patients with vitamin C deficiency (median 15.7 µmol/l, range 8.0–22.7) received Fe<sub>iv</sub> (100 mg iron sucrose between 150 and 180 min of HD). After 4 weeks of oral supplementation, the levels of vitamin C were comparable with those of controls (60.1 µmol/l, range 47.4–70.9). Patients were subsequently treated with (1) Fe<sub>iv</sub>, (2) Fe<sub>iv</sub> and continuous 2 mg/min C<sub>iv</sub> throughout HD, (3) saline (S), and (4) S+C<sub>iv</sub>. Plasma thiobarbituric acid reacting substances (TBARS) and vitamin C were assessed before, during and after FE<sub>iv</sub>(S), and 15, 30 and 60 min after infusion. Results: Fe<sub>iv</sub> induced a comparable rise in TBARS in patients with vitamin C deficiency (before Fe<sub>iv</sub>, 1.9 µmol/l, range 1.4–1.9; after Fe<sub>iv</sub>, 2.6 µmol/l, range 2.3–2.9; p < 0.01) and in those with normal vitamin C (before Fe<sub>iv</sub>, 1.9 µmol/l, range 1.7–2.1; after Fe<sub>iv</sub>, 2.6 µmol/l, range 2.5–2.9; p < 0.01). Fe<sub>iv</sub>+C<sub>iv</sub> resulted in a greater increase in TBARS (after Fe<sub>iv</sub>, 3.1 µmol/l, range 2.8–3.2) compared with Fe<sub>iv</sub> (p < 0.01). Conclusion: Iron sucrose-induced oxidative stress is comparable in HD patients with vitamin C deficiency and in those with normal vitamin C. We documented a pro-oxidative effect of vitamin C during Fe<sub>iv</sub>+C<sub>iv</sub> administration.

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              Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury.

              Multiple parenteral iron (Fe) formulations exist for administration to patients with end-stage renal disease. Although there are concerns regarding their potential toxicities, no direct in vitro comparisons of these agents exist. Thus, the present study contrasted pro-oxidant and cytotoxic potentials of four available Fe preparations: Fe dextran (Fe dext), Fe sucrose (Fe sucr), Fe gluconate (Fe gluc), and Fe oligosaccharide (Fe OS). Differing dosages (0.06 to 1 mg/mL) of each compound were added to either (1) isolated mouse proximal tubule segments, (2) renal cortical homogenates, or (3) cultured human proximal tubule (HK-2) cells (0.5- to 72-hour incubations). Oxidant injury (malondialdehyde generation) and lethal cell injury (percentage of lactate dehydrogenase release; tetrazolium dye uptake) were assessed. Effects of selected antioxidants (glutathione [GSH], catalase, dimethylthiourea (DMTU), and sodium benzoate also were assessed. Each test agent induced massive and similar degrees of lipid peroxidation. Nevertheless, marked differences in cell death resulted (Fe sucr > Fe gluc > Fe dext approximately Fe OS). This relative toxicity profile also was observed in cultured aortic endothelial cells. Catalase, DMTU, and sodium benzoate conferred no protection. However, GSH and its constituent amino acid glycine blocked Fe sucr-mediated cell death. The latter was mediated by mitochondrial blockade, causing free radical generation and a severe adenosine triphosphate depletion state. (1) parenteral Fes are highly potent pro-oxidants and capable of inducing tubular and endothelial cell death, (2) markedly different toxicity profiles exist among these agents, and (3) GSH can exert protective effects. However, the latter stems from GSH's glycine content, rather than from a direct antioxidant effect. Copyright 2002 by the National Kidney Foundation, Inc.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2006
                December 2006
                21 December 2006
                : 24
                : 5-6
                : 531-537
                Affiliations
                aDepartment of Medicine I and bInstitute for Clinical Biochemistry and Hematology, Charles University, Medical School and Teaching Hospital Pilsen, Pilsen, Czech Republic
                Article
                96474 Blood Purif 2006;24:531–537
                10.1159/000096474
                17077626
                b9e219f9-7d20-40cd-aa48-c7e2c9300776
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 12 May 2006
                : 16 August 2006
                Page count
                Tables: 5, References: 36, Pages: 7
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Vitamin C level,Intravenous iron,Oxidative stress,Hemodialysis
                Cardiovascular Medicine, Nephrology
                Vitamin C level, Intravenous iron, Oxidative stress, Hemodialysis

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