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      Effect of Chronic Therapy with Proteolytic Enzymes on Hypertension-Induced Renal Injury in the Rat Model of Goldblatt Hypertension

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          Abstract

          This study investigated the possible beneficial effect of intraperitoneal proteolytic enzyme administration on the development of hypertension-induced renal injury in the rat model of 2-kidney 1-clip (2K1C) Goldblatt hypertension. Male Wistar rats (120–150 g) underwent either sham surgery (control, n = 5) or clipping of the left renal artery. From day one 2K1C rats were randomized into 2 groups, placebo treatment (n = 7), and proteolytic enzyme treatment (n = 9). To the verum group a fixed mixture of trypsin (2.42 mg), bromelain (4.54 mg), and rutin (5.04 mg) dissolved in 2 ml of sterile 0.9% NaCl was administered intraperitoneally daily, while the placebo group received only vehicle. Rats were pair-fed. The duration of the study was 7 weeks. All 2K1C rats developed hypertension and the mean values of systolic blood pressure (SBP) did not differ significantly between the groups at any time recorded (SBP at sacrifice: controls 122.0 ± 8.5 mm Hg; placebo 191.4 ± 7.6 mm Hg; enzyme 180.5 ± 6.5 mm Hg). Enzyme treatment prevented the rise in proteinuria (controls 12.4 ± 2.6 mg/24 h; placebo 19.7 ± 3.9 mg/24 h; enzyme 12.2 ± 1.3 mg/24 h; p < 0.05) and ameliorated the increase in serum urea concentrations. Histomorphologically, signs of malignant nephrosclerosis were not found in control rats, while they were present in 4/7 (57%) of placebo-treated rats, but only in 1/9 (11%) of the enzyme-treated group. The volume fraction of renocortical interstitium was increased in both 2K1C groups in comparison with controls; however, enzyme treatment decreased the accumulation of interstitial tissue significantly (–22%) compared to placebo treatment. Cellular infiltration with mononuclear cells was also lower in the protease-treated group. To summarize, in the rat model of 2K1C hypertension, systemic treatment with proteases ameliorates the severity of nephrosclerosis and tubulointerstitial fibrosis in the non-clipped kidney, as well as proteinuria, without affecting high blood pressure.

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          Interactions between cytokines and α2-macroglobulin

           Keith James (1990)
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            Author and article information

            Journal
            AJN
            Am J Nephrol
            10.1159/issn.0250-8095
            American Journal of Nephrology
            S. Karger AG
            0250-8095
            1421-9670
            1998
            December 1998
            09 December 1998
            : 18
            : 6
            : 570-576
            Affiliations
            a Clinic of Pharmacotherapy, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia; b Institute of Pathology, University of Würzburg, Germany, c Clinic of Internal Medicine IV, University of Nürnberg-Erlangen, Germany; d Transplantation Institute, Warsaw, Poland, and e Department of Nephrology, Clinic of Internal Medicine, University of Würzburg, Germany
            Article
            13411 Am J Nephrol 1998;18:570–576
            10.1159/000013411
            9845840
            © 1998 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: 29, Pages: 7
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/13411
            Categories
            Laboratory Investigation

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