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      Effects of Defibrotide on Renal Function and Urinary Prostanoid Excretion in Ciclosporin-Treated Rats

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          Abstract

          Defibrotide (DF) has been proposed as a new antithrombotic agent in renal transplantation. Because it was also found to increase prostacyclin synthesis, a reduction in ciclosporin (CS) nephrotoxicity could be supposed. To ascertain this hypothesis, renal function and urinary prostanoids were evaluated in four groups of rats after 10 days of oral treatment (doses in mg/kg/day): CS 50 (group A), CS 50 + DF 400 (group B), DF 400 (group C) and controls (group D). Compared to controls, creatinine clearance (C<sub>Cr</sub>) was significantly lower in groups A and B (In C<sub>Cr</sub>: A = 6.62 ± 0.28, B = 6.83 ± 0.24 vs. 8.17 ± 0.13 μl/min, p < 0.01), whereas it did not change in group C (8.03 ± 0.24 μl/min). The urinary excretion of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) was significantly (p < 0.05) higher in group A (In PGE<sub>2</sub>: 3.98 ± 0.98 nmol/mol Cr) and more evidently in groups B and C (6.89 ± 0.38 and 6.01 ± 0.32 nmol/mol Cr, respectively) compared to controls (1.43 ± 0.45 nmol/mol Cr). The urinary excretion of 6-keto-PGF<sub>1</sub>α and of thromboxane B<sub>2</sub> (TxB<sub>2</sub>) were higher only in groups A and B (In 6-keto-PGF<sub>1α</sub> and In TxB<sub>2</sub>: A = 6.45 ± 0.22 and 4.97 ± 0.20, B = 7.06 ± 0.31 and 5.43 ± 0.41 vs. group D = 5.53 ± 0.22 and 3.79 ± 0.42 nmol/mol Cr; p < 0.05). The 6-keto-PGF<sub>1α</sub>/Tx molar ratio was not significantly affected, although a trend for a reduction in the ratio was found in the treated rats. In conclusion, DF enhanced urinary prostanoid excretion in CS-treated rats but did not significantly affect renal function.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1991
          1991
          11 December 2008
          : 59
          : 3
          : 477-481
          Affiliations
          aInstitute of Semeiotica Chirurgica and bInstitute of Clinica Medica II, University of Padua, Italy
          Article
          186612 Nephron 1991;59:477–481
          10.1159/000186612
          1758541
          © 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: 5
          Categories
          Original Paper

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