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      Native and Oxidized Low–Density Lipoproteins Enhance Superoxide Production from Diabetic Rat Glomeruli

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          Abstract

          Oxygen free radicals have been implicated in mediating diabetic complications, and patients with diabetic nephropathy frequently show increased levels of circulating and oxidized low–density lipoproteins (LDL). In the present study, we measured the superoxide production of glomeruli isolated from poorly controlled diabetic (streptozotocin) rats sacrificed 1 week and 1, and 3 months after the induction of diabetes. The animals were stimulated with native and oxidized LDL isolated from normal humans with normolipidemia. The superoxide ion was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal conditions, and this production increased further with the progression of diabetes. Stimulation with either LDL or oxidized LDL enhanced superoxide production by diabetic glomeruli, with oxidized LDL being more potent than LDL. Our results suggest that oxidized LDL may play important roles in the pathogenesis of diabetic nephropathy through enhanced generation of oxygen free radicals.

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          Increased oxidizability of plasma lipoproteins in diabetic patients can be decreased by probucol therapy and is not due to glycation.

          Alexander Babiy, Janusz M Gebicki, David Sullivan … (1992)
          Atherosclerosis is considered to be the major complication of diabetes mellitus. Since diabetic patients have increased blood levels of lipid peroxidation products we investigated whether the susceptibility of blood components to oxidation is altered in this disease. We analysed the parameters characterizing the extent of oxidative change and the antioxidant status of low density lipoprotein (LDL) and high density lipoprotein (HDL) in a group of diabetic patients and in a control population. LDL oxidizability was significantly higher for patients (P = 0.001) than for individuals in the control group. There were no significant differences in the alpha-tocopherol content or levels of performed peroxides in LDL samples isolated from diabetic patients and control individuals which could account for this effect. Similarly, LDL glycation, common in diabetes mellitus, was not responsible, since LDL glycated in vitro was more rather than less resistant to oxidation. Even the presence of unbound glucose at normal or elevated physiological concentrations had a delaying effect on the oxidation of LDL. The increased oxidizability of LDL isolated from diabetic patients could be reduced to control levels by a 6-week standard treatment with Probucol, originally applied to reduce their blood cholesterol.
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            Regulation of Heparin Binding-Epidermal Growth Factor-like Growth Factor Gene Expression by LDL and Oxidized LDL in Rat Mesangial Cells

            M.S. Tan, Y.J. Lee, S.J. Shin … (1994)
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              Author and article information

              Journal
              Journal ID (publisher-id): KBR
              Journal ID (nlm-ta): Kidney Blood Press Res
              Journal ID (doi): 10.1159/issn.1420-4096
              Title: Kidney and Blood Pressure Research
              Publisher: S. Karger AG
              ISSN (Print): 1420-4096
              ISSN (Electronic): 1423-0143
              Publication date Subscription-year: 2000
              Publication date (Print): 2000
              Publication date (Electronic): 24 March 2000
              Volume: 23
              Issue: 2
              Pages: 133-137
              Affiliations
              Departments of aInternal Medicine and bBiology, Kaohsiung Medical College, Kaohsiung, Taiwan
              Article
              Publisher ID: 25966 Other ID: Kidney Blood Press Res 2000;23:133–137
              DOI: 10.1159/000025966
              PubMed ID: 10765116
              SO-VID: 55a06376-202f-4aa6-bf18-7f68ec54bffe
              Copyright © © 2000 S. Karger AG, Basel
              License:

              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: 5, References: 23, Pages: 5
              Categories
              Subject: Fourth Asian Nephrology Forum

              ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
              Keywords: Superoxide,Diabetic rat glomeruli,Low–density lipoproteins
              Data availability:
              ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
              Keywords: Superoxide, Diabetic rat glomeruli, Low–density lipoproteins

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