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      Salvage of Cyclosporine A-Induced Oxidative Stress and Renal Dysfunction by Carvedilol

      ,

      Nephron

      S. Karger AG

      Cyclosporine A, Nephrotoxicity, Oxidative stress, Renal dysfunction, Carvedilol, Antioxidant

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          Abstract

          Background: Cyclosporine A (CsA) is the first-line immunosuppressant employed for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA nephrotoxicity. The present study was designed to investigate effects of carvedilol, a third-generation β-blocker with potent free radical-scavenging activity on CsA-induced oxidative stress and resultant renal dysfunction in a rat model of chronic CsA nephrotoxicity. Methods: Carvedilol (2.0 and 4.0 mg/kg i.p.) and propranolol (10 mg/kg i.p.) were administered to separate group of animals 24 h before and concurrently with CsA (20 mg/kg s.c.) for 21 days. Renal function was assessed by estimating plasma creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Tissue lipid peroxidation was measured as thiobarbituric acid-reacting substances (TBARS). Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin, PAS and Masson’s trichrome stained sections of the kidneys. Results: CsA (20 mg/kg s.c) administration for 21 days produced elevated levels of TBARS and deteriorated renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle-treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriolopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. Propranolol neither decreased TBARS nor improved the renal dysfunction and morphological changes induced by CsA. Both doses of carvedilol markedly reduced elevated levels of TBARS, whereas the higher dose of carvedilol significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. Conclusion: These data clearly indicate the renoprotective potential of carvedilol in CsA-induced nephrotoxicity and suggest a significant contribution of its antilipoperoxidative property in this beneficial effect.

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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
          September 2002
          26 September 2002
          : 92
          : 3
          : 685-692
          Affiliations
          Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
          Article
          64095 Nephron 2002;92:685–692
          10.1159/000064095
          12372956
          © 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: 4, Tables: 2, References: 39, Pages: 8
          Product
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/64095
          Categories
          Preliminary Communication

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