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      Hippurate Metabolism as a Hydroxyl Radical Trapping Mechanism in the Rat Kidney

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      Kidney and Blood Pressure Research

      S. Karger AG

      Hippurate, Benzoate, Hydroxyl radical, Hydroxybenzoates

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          Abstract

          Hippurate (Hip) is considered to be the end product of benzoate (BA) metabolism. However, the kidney is able to metabolize Hip. Although only Hip but no BA is present in the blood, rat urine contains under normal conditions less Hip (about 0.4 m M) than BA (about 4.5 m M) and of hydroxylated derivatives of BA (hydroxy-BAs = HB and dihydroxy-BAs = DHB). Generation of HBs and DHBs is the result of radical substitution by free OH radicals (·OH). Thus, rate of synthesis of HBs and DHBs may reflect the production rate of ·OH in the kidney. ·OH generation is elevated following ischemic stress. Therefore, production of HBs and DHBs can be expected to be elevated in postischemic injury. The validity of this assumption was tested in vitro on isolated tubular segments and in vivo in the rat. Metabolism of Hip at 0.1 mmol l<sup>–1 </sup>(0.1 m M) as well as of BA resulted in enlarged production of both HBs (especially 3-HB and 4-HB) and of DHBs (especially 2,6-DHB). Production of 2,3- and especially of 2,5-DHB was elevated in the presence of high concentration (1.0 m M) of salicylate (2-HB) only. In vivo both in acute (120 min) and in chronic (5 days) experiments ligation of one renal artery for 30 respectively 60 min resulted in enlarged excretion of HBs and DHBs, especially of 2,6- and 3,5-DHB. This finding is noteworthy since (a) formation of 2,6-DHB necessitates as precursor salicylate which could not be detected in our experiments and (b) the spontaneous attack of ·OH upon the benzol ring would prefer the positions 2,3- 2,5- and 3,4-. Therefore, the existence of regulating factor(s) guiding OH groups to definite positions is a distinct possibility. These results indicate that metabolism of Hip leading to hydroxylated BAs may be a renoprotective mechanism against attack of ·OH in reoxygenated renal tissue.

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          Benzoate modulates renal and extrarenal nitrogen flow: Metabolic mechanisms

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            Author and article information

            Journal
            KBR
            Kidney Blood Press Res
            10.1159/issn.1420-4096
            Kidney and Blood Pressure Research
            S. Karger AG
            1420-4096
            1423-0143
            2001
            2001
            29 August 2001
            : 24
            : 3
            : 149-158
            Affiliations
            Department of Physiology, University of Kiel, Germany
            Article
            54222 Kidney Blood Press Res 2001;24:149–158
            10.1159/000054222
            11528207
            © 2001 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: 6, References: 24, Pages: 10
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/54222
            Categories
            Original Paper

            Cardiovascular Medicine, Nephrology

            Hydroxybenzoates, Hydroxyl radical, Benzoate, Hippurate

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