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      Protective Effect of HMG-CoA Reductase Inhibitor on Experimental Renal Ischemia-Reperfusion Injury

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          Abstract

          Background: Increasing evidence supports an important role for inflammation in the pathogenesis of renal ischemia-reperfusion injury (IRI). Recently, HMG-CoA reductase inhibitors, ‘statins’, have demonstrated anti-inflammatory effects independent of cholesterol-lowering. Hypothesis: We tested the hypothesis that a statin would improve outcome in a murine model of renal IRI. Upon finding a protective effect, we tested the hypothesis that the mechanisms by which statins protected in renal IRI was by reducing neutrophil and macrophage infiltration and upregulating the anti-inflammatory cytokine IL-6. Methods: Cerivastatin at various dosing regimens was administered to NIH Swiss mice to evaluate the effects on renal IRI. Analysis of renal structure, function, neutrophil and macrophage infiltration, cytokine production, as well as mortality was performed in cerivastatin- and saline-treated groups. Results: Primary: Cerivastatin pretreatment for 3 days led to a significant improvement in renal function, tubular injury as well as survival after IRI compared to saline-treated mice. Secondary: Neutrophil and macrophage infiltration into kidney tissue was similar in both groups. IL-6 was markedly upregulated early in the kidneys of statin-treated compared to saline-treated mice. Conclusion: These data demonstrate that a statin compound can improve the course of ischemic acute renal failure. Induction of protective molecules such as IL-6 may underlie this effect.

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          Most cited references 3

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          Identification of the CD4+ T cell as a major pathogenic factor in ischemic acute renal failure

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            Ischemic acute renal failure

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              MHC class II regulation in vivo in the mouse kidney

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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
                2003
                October 2002
                23 October 2002
                : 23
                : 1
                : 13-17
                Affiliations
                aDivision of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Md. and bDivision of Nephrology, Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis, Minn., USA
                Article
                66301 Am J Nephrol 2003;23:13–17
                10.1159/000066301
                12373076
                © 2003 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: 18, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/66301
                Categories
                Original Article: Basic Sciences

                Cardiovascular Medicine, Nephrology

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