1
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Tryptophan Metabolism via the Kynurenine Pathway in Experimental Chronic Renal Failure

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Kidneys are involved in tryptophan (TRP) metabolism in two ways. They eliminate TRP derivatives on the one hand, and they produce several enzymes taking part in TRP metabolism mainly via the kynurenine pathway on the other. The aim of the present study was to examine the time-course of changes in the peripheral kynurenine products degradation during experimental chronic renal failure in rats. Methods: Tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, anthranilic acid and quinolinic acid were determined in plasma using high-performance liquid chromatography technique with UV, fluorescence and electrochemical detection. Results: A decreased TRP level and significant increase in kynurenine pathway metabolite concentrations in plasma of uremic rats were found. Conclusions: Substantial disturbances in the peripheral kynurenic pathway were observed in experimental chronic renal failure. They may contribute to several symptoms of uremia.

          Related collections

          Most cited references 4

          • Record: found
          • Abstract: found
          • Article: not found

          Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.

          3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of hydrogen peroxide and hydroxyl radical is involved in the toxicity. Measurement of peroxide levels revealed that 3-HK caused intracellular accumulation of peroxide, which was largely attenuated by application of catalase. The peroxide accumulation and cell death caused by 1-10 microM 3-HK were also blocked by pretreatment with allopurinol or oxypurinol, suggesting that endogenous xanthine oxidase activity is involved in exacerbation of 3-HK neurotoxicity. Furthermore, NADPH diaphorase-containing neurons were spared from toxicity of these concentrations of 3-HK, a finding reminiscent of the pathological characteristics of several neurodegenerative disorders such as Huntington disease. These results suggest that 3-HK at pathologically relevant concentrations renders neuronal cells subject to oxidative stress leading to cell death, and therefore that this endogenous compound should be regarded as an important factor in pathogenesis of neurodegenerative disorders.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Cloning and Functional Expression of a Soluble Form of Kynurenine/α -Aminoadipate Aminotransferase from Rat Kidney

              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              2-Oxoacids Regulate Kynurenic Acid Production in the Rat Brain

                Bookmark

                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2002
                March 2002
                25 February 2002
                : 90
                : 3
                : 328-335
                Affiliations
                Departments of aPharmacodynamics, and bII General Surgery, Medical Academy of Bialystok, Poland
                Article
                49069 Nephron 2002;90:328–335
                10.1159/000049069
                11867954
                © 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: 31, Pages: 8
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/49069
                Categories
                Original Paper

                Comments

                Comment on this article