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      Effects of Oral Administration of Heparan Sulphate in the Rat Remnant Kidney Model

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          Abstract

          Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 ± 22 vs. 80 ± 54 mg/24 h , p < 0.01), lower urea plasma levels (75 ± 34 vs. 134 ± 105 mg/dl, p < 0.01) and higher creatinine clearance (66 ± 15 vs. 47 ± 21 ml/min · 10<sup>2</sup>, p < 0.05) than control rats. Remnant kidney weight (2.3 ± 1.1 vs. 1.3 ± 0.2 g, p < 0.01) and heart weight (1.3 ± 0.2 vs. 1.1 ± 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 ± 19 vs. 115 ± 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1999
          March 1999
          26 February 1999
          : 81
          : 3
          : 310-316
          Affiliations
          aDipartimento di Medicina Interna, Università di Pisa, bLaboratori Baldacci, Pisa, cDivisione Nefrologica, AO Pisana, Pisa, Italia
          Article
          45298 Nephron 1999;81:310–316
          10.1159/000045298
          10050086
          © 1999 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: 24, Pages: 7
          Product
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/45298
          Categories
          Original Paper

          Cardiovascular Medicine, Nephrology

          Heparan sulphate, Heparins, Remnant kidney, Chronic renal failure

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