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      Ionic Radiocontrast Media Disrupt Intercellular Contacts via an Extracellular Calcium-Independent Mechanism

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          Abstract

          Direct cytotoxic effects of radiocontrast (RC) agents have been implicated in radiocontrast nephropathy (RCIN). The interaction between extracellular calcium, which plays a central role in intercellular contacts, and the in vitro toxicity of RC was tested in Madin-Darby canine kidney (MDCK) cell monolayers grown on permeable supports. Cell viability was determined by trypan blue exclusion. The function of intercellular junctions was assessed by measuring the electrical transmonolayer resistance (TMR). The cell contacts were examined with indirect immunofluorescence microscopy using antibodies against the junctional proteins E-cadherin, ZO-1 and occludin. The ionic RC agents diatrizoate and ioxaglate (74 mg iodine/ml), but not the nonionic compounds iohexol or iodixanol, decreased ionized calcium (Ca<sup>2+</sup>) in the incubation media from 1.48 ± 0.04 m M (control) to 0.89 ± 0.06 m M (diatrizoate), respectively to 1.05 ± 0.08 m M (ioxaglate). Diatrizoate, and to a lesser extent ioxaglate, reduced the number of viable MDCK cells and showed a redistribution of the E-cadherin, ZO-1 and occludin immunofluorescence signal with a parallel decrease of the TMR indicating an impaired monolayer integrity. A similar reduction of extracellular Ca<sup>2+</sup> through EGTA failed to reproduce these effects. Conversely, raising Ca<sup>2+</sup> in diatrizoate-containing media to control levels did not abrogate its toxicity. In conclusion, the ionic RC agents diatrizoate and ioxaglate, but not the nonionic compounds iohexol or iodixanol, reduce extracellular Ca<sup>2+</sup> in vitro. However, this reduction of Ca<sup>2+</sup> does not explain their cytotoxic effects which could contribute to the pathogenesis of RCIN in vivo by opening intercellular junctions.

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          Cadherins: a family of Ca2+-dependent adhesion molecules

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            Author and article information

            Journal
            EXN
            Nephron Exp Nephrol
            10.1159/issn.1660-2129
            Cardiorenal Medicine
            S. Karger AG
            1660-2129
            2002
            2002
            30 May 2002
            : 10
            : 3
            : 209-215
            Affiliations
            Department of Medicine, University of Heidelberg, Germany
            Article
            58347 Exp Nephrol 2002;10:209–215
            10.1159/000058347
            12053122
            © 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: 3, Tables: 2, References: 23, Pages: 7
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/58347
            Categories
            Original Paper

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