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      Metabolic Heterogeneity of Isolated Cortical and Juxtamedullary Glomeruli in Adriamycin Nephrotoxicity

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          Abstract

          The anticancer drug adriamycin (ADR) is selectively toxic to glomerular cells when administered intravenously (5 mg/kg b.w.) to female MWF/Ztm rats. Recent data have shown that the proteinuria associated with the lesion does not occur in cortical glomeruli, suggesting the selective injury of juxtamedullary glomeruli. In the present study, the effect of ADR on glomerular metabolism was studied with special reference to possible differences between cortical and juxtamedullary glomeruli. On day 7 after ADR treatment, cortical and juxtamedullary glomeruli were separately isolated by the sieving method and <sup>14</sup>C glucose oxidation to <sup>14</sup>C0<sub>2</sub> and the incorporation of <sup>3</sup>H proline into macromolecules were measured in vitro and used to study target selective injury in ADR-treated rats compared to control rats. The investigations revealed differences in the response of cortical and juxtamedullary glomeruli to ADR. ADR treatment increased proline incorporation over a 4-hour incubation period in both glomerular populations compared to controls, but the effect was significantly (p < 0.05) more pronounced in juxtamedullary glomeruli (juxtamedullary: 187 ± 8% of control; cortical: 167 ± 4% of control). Glucose oxidation was enhanced after 4 h only in juxtamedullary glomeruli (juxtamedullary: 132 ± 3% of control; cortical: 82 ± 10% of control). These data show that glomerular damage caused by ADR is associated with a stimulating effect on glomerular metabolism which is more marked in juxtamedullary than in cortical glomeruli, thus indicating a heterogenous response of different glomerular populations and supporting the concept that the selective damage of juxtamedullary glomeruli accounts for the proteinuria.

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          Author and article information

          Journal
          KBR
          Kidney Blood Press Res
          10.1159/issn.1420-4096
          Kidney and Blood Pressure Research
          S. Karger AG
          1420-4096
          1423-0143
          1991
          1991
          07 November 2008
          : 14
          : 1-2
          : 48-54
          Affiliations
          aLaboratory of Experimental Nephrology, Division of Nephrology, Department of Internal Medicine, Medical School Hannover, FRG; bNephrotoxicity Research Group, Robens Institute, University of Surrey, Guildford, UK
          Article
          173387 Renal Physiol Biochem 1991;14:48–54
          10.1159/000173387
          1706105
          © 1991 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
          Pages: 7
          Categories
          Original Paper

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