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      Effect of FK 506 in the Treatment of Autoimmune Glomerulonephritis in Brown Norway Rats

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          Abstract

          Mercuric chloride (HgCl<sub>2</sub>) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. The effects of a new immunosuppressant, FK 506, on this model of glomerulonephritis were studied. BN rats were treated with HgCl<sub>2</sub> according to a standard protocol (HgCl<sub>2</sub> 1 mg/kg s.c. 3 times/week). FK 506 was inoculated subcutaneously daily from day 15 to day 28. Animals were divided into 4 groups: group 1, rats were treated with normal saline alone and sacrificed on day 28; group 2, rats were treated with HgCl<sub>2</sub> alone and sacrificed on day 14; group 3, rats were treated with HgCl<sub>2</sub> alone and sacrificed on day 28, and group 4, rats were treated with HgCl<sub>2</sub> and FK 506 (from day 15 to day 28) and sacrificed on day 28. Rats developed proteinuria by day 7, which reached a plateau level by day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Treatment with FK 506 (1 mg/kg s.c. daily) resulted in a remarkable reduction in proteinuria on day 28 (493.5 ± 48.3 vs. 24.4 ± 13.5 mg/day) and an improvement in the morphological lesions. These findings suggest that FK 506 could be useful in the treatment of some human glomerulonephritides.

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          Most cited references 2

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          Susceptibility to Mercuric Chloride-Induced Glomerulonephritis is Age-Dependent: Study of the Role of IFN-γ

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            • Record: found
            • Abstract: not found
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            Nitric Oxide Contributes to Tissue Injury in Mercuric Chloride-Induced Autoimmunity

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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
              April 1999
              31 March 1999
              : 81
              : 4
              : 421-427
              Affiliations
              aFifth Department of Internal Medicine, Hyogo College of Medicine, Hyogo, bSchool of Allied Health Sciences, Faculty of Medicine, and cFirst Department of Medicine, Osaka University, Osaka, Japan
              Article
              45326 Nephron 1999;81:421–427
              10.1159/000045326
              10095178
              © 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: 5, References: 28, Pages: 7
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/45326
              Categories
              Original Paper

              Cardiovascular Medicine, Nephrology

              Brown Norway rat, FK 506, Mercuric chloride

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