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

      Free Reactive Oxygen Species and Nephrotoxicity of Contrast Agents

      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: The nephrotoxicity induced by contrast media remains a serious clinical problem, and the underlying mechanism has not been completely understood. Experimental and clinical investigations suggest that reactive oxygen species (ROS) are critical determinants of radiocontrast nephropathy (RCN), and that antioxidants can prevent this damage. Methods: Cultured human proximal renal tubule cells (HK-2) were exposed to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) at different concentrations. H<sub>2</sub>O<sub>2</sub>-induced tubular DNA damage was examined in the presence of the antioxidant MESNA (sodium-2-mercaptoethane sulphonate). The induction of DNA damage was measured with the alkaline comet assay (single cell gel electrophoresis). We also studied 12 patients with stable renal impairment (median baseline creatinine 296 µmol/l; range: 203–495 µmol/l) undergoing cardiac catheterization/intervention prospectively. Patients received 800 mg MESNA intravenously 30 min before exposure to the contrast agent in addition to 0.9% saline hydration. Results: In the cell cultures, oxidative stress on HK-2 cells induced increased DNA migration in the comet assay. Treatment of tubular cells with the antioxidant MESNA prior to the addition of H<sub>2</sub>O<sub>2</sub> significantly reduced DNA migration in the comet assay. In the clinical study, treatment of the patients with MESNA prevented the adverse renal effect of contrast media (median serum creatinine 293; range: 187–433 µmol/l) 48 h after coronary angiography/intervention. Conclusion: Both the in vivo and the in vitro studies suggest that the ROS-mediated renal injury could be inhibited by a potent antioxidant such as MESNA.

          Related collections

          Most cited references 7

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

          Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA.

          The endogenous production of oxidative damage in DNA by free radicals released as a by-product of respiration is a likely cause of mutations which, if they occur in appropriate genes, may lead to cancer. Using an endonuclease specific for oxidized pyrimidines, in conjunction with the highly sensitive method of single cell gel electrophoresis, we have detected significant oxidative damage in untreated, freshly isolated lymphocytes from normal, healthy individuals.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney

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

              Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering.

              Increased oxidative stress is a major characteristic of hypercholesterolemia-induced atherosclerosis. The oxidative environment is mainly created by the production of reactive oxygen species, which are assumed to mediate vascular tissue injury. Oxidative DNA damage resulting from free radical attack remains, however, a poorly examined field in atherosclerosis. Male New Zealand White rabbits were fed a cholesterol-rich diet (0.3%) for 24 weeks. The induced atherosclerotic plaques showed elevated levels of the DNA damage marker 7,8-dihydro-8-oxoguanine (8-oxoG) as demonstrated by immunohistochemistry. 8-oxoG immunoreactivity was found predominantly in the superficial layer of the plaque containing numerous macrophage-derived foam cells but not in the media or in arteries of age-matched control animals. Alkaline single-cell gel electrophoresis revealed that the number of DNA strand breaks was significantly higher in the plaque as compared with control samples of normolipemic animals. These changes were associated with the upregulation of DNA repair enzymes (poly[ADP-ribose] polymerase-1, p53, phospho-p53 [phosphorylated at Ser392], and XRCC1 [x-ray repair cross-complementing 1]). DNA strand breaks normalized after 4 weeks of dietary lipid lowering. However, a significant reduction of 8-oxoG immunoreactivity was only observed after a prolonged period of lipid lowering (12 to 24 weeks). Repair pathways started to decline progressively when cholesterol-fed animals were placed on a normal diet. In conclusion, oxidative DNA damage and increased levels of DNA repair, both associated with diet-induced hypercholesterolemia, are strongly reduced during dietary lipid lowering. These findings may provide a better insight into the benefits of lipid-lowering therapy on plaque stabilization.
                Bookmark

                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
                2004
                April 2004
                12 August 2004
                : 27
                : 3
                : 167-171
                Affiliations
                Nephrology, Medical Faculty University of Ulm, Ulm, Germany
                Article
                79805 Kidney Blood Press Res 2004;27:167–171
                10.1159/000079805
                15256812
                © 2004 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, References: 15, Pages: 5
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/79805
                Categories
                NephroPharmacology 7 Meeting

                Comments

                Comment on this article