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      Vitamin E Protects Renal Antioxidant Enzymes and Attenuates Glomerulosclerosis in Adriamycin-Treated Rats

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          Abstract

          Background/Aims: In the rat Adriamycin model of chronic renal failure, the development of glomerulosclerosis and tubulointerstitial lesions is accompanied by decreased activities and mRNA levels of the antioxidant enzymes. In this study, we investigated the effect of oral vitamin E supplementation on antioxidant enzyme activities in both the cortex and isolated glomeruli from Adriamycin-treated rats. Methods: Glomerulosclerosis, tubulointerstitial lesions and ferric iron deposits were evaluated by histochemical staining methods, and antioxidant enzyme activities were measured by spectrophotometry. Results: Vitamin E supplementation of the normal diet attenuates Adriamycin-induced glomerulosclerosis and tubulointerstitial lesions, but not proteinuria and serum total cholesterol, low-density lipoprotein cholesterol, triglycerides and total protein concentrations. In the cortex, vitamin E completely prevented a decrease in enzyme activity for Cu/Zn superoxide dismutase and catalase, and partly for Mn superoxide dismutase and glutathione peroxidase. In the glomeruli, vitamin E completely prevented a decrease in activity for Cu/Zn superoxide dismutase, catalase and glutathione peroxidase, and partly for Mn superoxide dismutase. Conclusion: Dietary supplementation of vitamin E protects the activities of antioxidant enzymes in the kidney cortex and glomeruli, and attenuates the evolution towards terminal renal failure in rats treated with Adriamycin.

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          Most cited references 3

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          Renal Antioxidant Enzymes and Fibrosis-Related Markers in the Rat Adriamycin Model

          Excessive generation of reactive oxygen intermediates can induce changes in the cellular antioxidant defence system. In this study we examine the antioxidant enzyme status and the expression of fibrosis-related marker proteins in the Adriamycin model of chronic renal failure in the rat. Twenty weeks after Adriamycin treatment, rats have overt nephrotic syndrome and renal failure with development of tubulo-interstitial fibrosis and glomerulosclerosis. Lipids accumulate in blood and in both glomeruli and tubulo-interstitial tissue. Desmin and α-smooth muscle actin expression increases in glomeruli and in the tubulo-interstitial area. Renal cortex antioxidant enzyme activities are decreased 20 weeks after Adriamycin injection (to 41% for catalase, to 56% for total superoxide dismutase and to 69% for glutathione peroxidase). The mRNA levels of catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1 evaluated by Northern blot are decreased by more than 50% for catalase, Cu/Zn-superoxide dismutase and glutathione peroxidase-1. We conclude that in the rat Adriamycin-induced model of chronic renal failure with fibrosis, the combination of decreased antioxidant enzyme status in renal cortex with high concentrations of lipids in blood and renal tissue facilitates oxidative damage. Development of fibrosis is paralleled by increased expression of desmin and α-smooth muscle actin.
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            Role of free radicals in the pathogenesis of lipid-induced glomerulosclerosis in rats.

            We examined whether a high-cholesterol (HC) diet causes glomerulosclerosis in rats, and investigated the role of free radicals and lipid peroxidation in lipid-induced glomerulosclerosis.
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              Effect of Vitamin E on Adriamycin- Induced Nephrotoxicity at the Ultrastructural Level in Guinea Pigs

              It is known that Adriamycin, which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in several organs. In this study, we have established that vitamin E has some beneficial effects on the kidney by protecting it from some of the toxcity induced by Adriamycin. A study was carried out which comprised one control group and two experimental groups of guinea pigs. In the experiment Adriamycin was administered either alone (group II) or together with vitamin E (group III). The results of groups II and III were compared with controls (group I). The kidneys were subsequently removed and examined by routine electron microscopic techniques. We found that vitamin E administered together with Adriamycin could reverse some of the degenerative changes caused by Adriamycin.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2002
                May 2002
                02 May 2002
                : 91
                : 1
                : 129-133
                Affiliations
                aDepartment of Human Anatomy, bLearning Resource Centre and cDepartment of Nephrology, Vrije Universiteit Brussel, Belgium
                Article
                57614 Nephron 2002;91:129–133
                10.1159/000057614
                12021529
                © 2002 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.

                Page count
                Figures: 2, Tables: 1, References: 23, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/57614
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