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      Effect of Vitamin E and Vitamin C Supplementation on Antioxidative State and Renal Glomerular Basement Membrane Thickness in Diabetic Kidney

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          Abstract

          The aim of this study was to analyze the effect of vitamins C and E on malondialdehyde (MDA) content and activities of key antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as glomerular basement membrane (GBM) thickness in streptozotocin-induced diabetic kidney in rats. Wistar male rats were divided into following groups (12 rats each): the control, diabetic rats, diabetic rats whose drinking water was supplemented with vitamin C in a dose of 1.0 g/l or diet was supplemented with 200 mg of vitamin E/100 g fodder. Body weight, blood glucose and HbA1C levels and 24-hour urinary albumin excretion (UAE) were studied every week (0–12 weeks). After 6 and 12 weeks, MDA content and activities of SOD, CAT and GSH-Px were measured in the kidney homogenate supernatants. Electron micrographs of glomeruli were scanned and morphometric investigations were performed by means of computer image analysis system to compare GBM thickness. The blood glucose and HbA1C concentrations and UAE in diabetic rats were significantly higher than in the control group. An increase in the MDA level and decrease in the SOD, CAT and GSH-Px activities in the kidney of diabetic rats were observed after 6 and 12 weeks of experiment. Administration of vitamins C and E did not affect body weight, blood glucose and HbA1C levels. Both vitamin C and vitamin E decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of diabetic rats as well as reduced UAE, decreased kidney weight and GBM thickness. The results indicate the potential utility of antioxidant vitamins in the protection against the development of diabetic nephropathy.

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          Most cited references 7

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          Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins.

          Reperfusion of the ischemic myocardium results in structural changes in the capillary bed, which may contribute to decreased microcirculatory flow ("no reflow"). This study was designed to correlate the endothelial cell shape changes with both oxidative stress and lipid peroxidation and to evaluate the beneficial potential of Trolox (a hydrophilic analogue of alpha-tocopherol) and ascorbic acid. Isolated buffer-perfused rat hearts were made ischemic for 45 min and then reperfused with 100 microM Trolox and/or 100 microM ascorbic acid. Morphological changes were quantified by measuring capillary cross-sectional areas. Increased myocardial content of oxidized glutathione and its release into the coronary effluent were used as indices of oxidative stress. Myocardial MDA, an end product of lipid peroxidation, was also measured. Luminal membrane blebs and capillary "constriction" in the ischemic groups occurred when there was no change in either glutathione status or MDA concentrations. Reperfusion altered the redox state of the heart sufficiently to induce lipid peroxidation. It also induced endothelial cell swelling and a reduction in luminal area. Ascorbic acid was a more effective antioxidant than Trolox as it significantly reduced both oxidative stress and ultrastructural injury. The combined antioxidant treatment returned both the stress ratio and the capillary measurements to control values. We conclude that endothelial cell swelling correlates with the degree of oxidative stress and that antioxidant vitamins reduce membrane damage by preventing lipid peroxidation.
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            Antioxidants reverse the antiproliferative effect of high glucose and advanced glycosylation end products in cultured rat mesangial cells.

            High glucose and elevated levels of advanced glycosylation end products (AGEs) exert an antiproliferative effect on cultured mesangial cells. In view of the role of oxygen free radicals in the pathogenesis of diabetic nephropathy, we tested whether two endogenous antioxidants, taurine and vitamin E, ameliorate the effects of an elevated ambient glucose and/or AGEs on mesangial cell growth in vitro. Regardless of whether cell proliferation was assayed by the incorporation of [3H]thymidine, direct cell counting or bromodeoxyuridine (BrdU) cell staining, both taurine and vitamin E reversed the inhibitory effect of high glucose and AGEs on mesangial cell growth. In conjunction with our previous studies indicating that taurine and vitamin E reduce collagen production in mesangial cells exposed to high glucose, these findings suggest that endogenous antioxidants attenuate diabetic glomerulosclerosis by interfering with the bioactivation of transforming growth factor-6.
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              Regulation of Collagen Synthesis in Human Dermal Fibroblasts in Contracted Collagen Gels by Ascorbic Acid, Growth Factors, and Inhibitors of Lipid Peroxidation

               J C Geesin (1993)
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2003
                December 2003
                17 November 2004
                : 95
                : 4
                : e134-e143
                Affiliations
                Departments and aClinics of Geriatrics, bPharmacology and Therapy, and cBiochemistry, L. Rydygier Medical University of Bydgoszcz; dDepartment of Forensic Medicine, Medical University of Łódź, and eDepartment of Molecular Biophysics, University of Łódź, Poland
                Article
                74840 Nephron Exp Nephrol 2003;95:e134–e143
                10.1159/000074840
                14694267
                © 2003 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: 5, Tables: 4, References: 30, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/74840
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