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      Why Hemodialysis Patients Are in a Prooxidant State? What Could Be Done to Correct the Pro/Antioxidant Imbalance

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          Abstract

          Oxidative stress which results from an imbalance between reactive oxygen species production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pathologies such as accelerated atherosclerosis, amyloidosis and anemia. In order to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be responsible for the imbalance between pro- and antioxidative mechanisms. The inflammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species contributing by this way to worsen the prooxidant status of uremic patients. Two factors largely contribute to the stimulation of the NADPH oxidase: hemoreactivity of the membrane and trace amounts of endotoxins. The antioxidant system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant system mainly by losses of (a) hydrophilic unbound small-molecular-weight substances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compounds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatibility of the dialysis system mainly by using a dialyzer with low hemoreactivity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achieved by oral or perdialytic supplementation. Vitamin E could be bound on dialyzer membrane. Alternatively, hemolipodialysis consists in loading HD patients with vitamin C or E via an ancillary circuit made of vitamin E-rich liposomes. The presence of liposomes could also facilitate the removal of hydrophobic prooxidative substances.

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          Antioxidants and atherosclerotic heart disease.

          Epidemiologic studies have provided evidence of an inverse relation between coronary artery disease and antioxidant intake, and vitamin E supplementation in particular. The oxidative-modification hypothesis implies that reduced atherosclerosis is a result of the production of LDL that is resistant to oxidation, but linking the reduced oxidation of LDL to a reduction in atherosclerosis has been problematic. Several important additional mechanisms may underlie the role of antioxidants in preventing the clinical manifestations of coronary artery disease (Fig. 2). Specifically, there is evidence that plaque stability, vasomotor function, and the tendency to thrombosis are subject to modification by specific antioxidants. For example, cellular antioxidants inhibit monocyte adhesion, protect against the cytotoxic effects of oxidized LDL, and inhibit platelet activation. Furthermore, cellular antioxidants protect against the endothelial dysfunction associated with atherosclerosis by preserving endothelium-derived nitric oxide activity. We speculate that these mechanisms have an important role in the benefits of antioxidants.
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            The role of lipid peroxidation and antioxidants in oxidative modification of LDL

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              Increase in Resting Levels of Superoxide Anion in the Whole Blood of Uremic Patients on Chronic Hemodialysis

              Recently, we developed a new method to measure the resting level of superoxide anion in whole blood using an ultrasensitive chemiluminescence analyzer and lucigenin amplification. The advantage of this method is that the assay system can be performed in the absence of leukocyte isolation and stimulant administration. In this study, we applied this method to measure the blood resting levels of superoxide anion in 104 uremic patients on chronic hemodialysis (CHD) and 98 sex- and age-matched healthy controls to clarify the influence of HD on blood levels of superoxide anion. Simultaneously, the plasma levels of copper, zinc superoxide dismutase (Cu,Zn-SOD), glutathion peroxidase (GPX), myeloperoxidase (MPO) and lactoferrin (Lacto-F) were measured. The results showed that the basal blood levels of superoxide anion, Cu,Zn-SOD, and MPO in CHD patients were significantly greater than those of healthy controls. However, there was no difference in the basal plasma levels of Lacto-F and GPX between CHD patients and healthy controls. One session of HD further increased the blood levels of superoxide anion, MPO, Lacto-F and Cu,Zn-SOD but not GPX. These results suggest that the blood levels of superoxide anion are higher in CHD patients and further increase after one session of HD. This mechanism should be studied further.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-8055-7083-1
                978-3-318-00584-4
                0253-5068
                1421-9735
                2000
                2000
                03 August 2000
                : 18
                : 3
                : 191-199
                Affiliations
                aBiochemistry Laboratory and bNephrology Department, Lapeyronie University Hospital, Montpellier (France)
                Article
                14418 Blood Purif 2000;18:191–199
                10.1159/000014418
                10859422
                ac4e1613-d774-4c34-83cf-604714ee3e2e
                © 2000 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
                Page count
                Figures: 3, References: 60, Pages: 9
                Categories
                Paper

                Cardiovascular Medicine,Nephrology
                Oxidative stress,Atherosclerosis,Hemodialysis,Antioxidant
                Cardiovascular Medicine, Nephrology
                Oxidative stress, Atherosclerosis, Hemodialysis, Antioxidant

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