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      Protective Effect of Three Xanthine Derivatives (Theophylline, Caffeine and Pentoxifylline) against the Cyclosporin A-lnduced Glomerular Contraction in Isolated Glomeruli and Cultured Mesangial Cells

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          Abstract

          Cyclosporin A (CyA), an immunosuppressive agent, induces in vivo a severe nephrotoxicity with large decrease in renal hemodynamics correlated with in vitro glomerular contraction. The aim of this study is to show the ability of three xanthine derivatives, caffeine, theophylline and pentoxifylline, to diminish the CyA-induced in vitro glomerular contraction. The use of isolated glomeruli and cultured rat mesangial cells permits us to evaluate by quantitative and qualitative morphometric analysis the contraction elicited either with CyA alone or with previous treatment with nontoxic concentrations of xanthine derivatives. Indirect immunofluorescence of actin filaments makes it possible to appreciate qualitative morphometric changes in mesangial cells. A 10-min pretreatment with caffeine, theophylline or pentoxifylline (10<sup>-4</sup> to 10<sup>-9</sup> M) abolishes the contraction elicited with 10<sup>-6</sup> M CyA. CyA alone induces -13.9% compared to CyA with 10<sup>-6</sup> M pentoxifylline which induces only -3.2% of reduction of planar glomerulus surface area after 30 min. Similar results were provided with cultured rat mesangial cells. As shown by indirect immunofluorescence xanthine derivatives prevent the cytoskeletal reorganization (α-actin) of cultured mesangial cells which occurs with CyA. The marked constriction induced by CyA in isolated glomeruli and mesangial cells can be prevented by xanthine derivatives.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1997
          1997
          23 December 2008
          : 77
          : 4
          : 427-434
          Affiliations
          aLaboratoire de Biologie Cellulaire, Faculté de Pharmacie et bService de Néphrologie Clinique, Hôpital Pellegrin, Bordeaux, France
          Article
          190320 Nephron 1997;77:427–434
          10.1159/000190320
          9434065
          © 1997 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: 8
          Categories
          Original Paper

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