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      Electron Paramagnetic Resonance Imaging of Oxidative Stress in Renal Disease

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          Abstract

          The importance of analyzing the kinetics of reactive oxygen species or related substances in vivo is increasing. Electron paramagnetic resonance (EPR) is currently a powerful method for in vivo, non-invasive analysis of oxidative stress. We have applied EPR imaging for murine renal ischemia-reperfusion injury, as a model of acute renal damage, and NF-E2-related factor 2 (Nrf2)-deficient mice, a model for chronic progressive renal disease. In the ischemia-reperfusion model, EPR imaging revealed that the renal radical-reducing activity showed only partial recovery when serum creatinine and BUN have recovered. In the Nrf2-deficient mice, we have revealed that the impaired antioxidant activity is brought by both Nrf2 deficiency and the aging process and may play a key role in the onset of autoimmune nephritis in this model. In addition, EPR imaging is recently being applied to the redox analysis of several nephrosis models, hypertensive rats and streptozotocin-induced diabetic rats. This article summarizes the nephrological application of EPR imaging and in vivo EPR.

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          Trapping of free radicals with direct in vivo EPR detection: a comparison of 5,5-dimethyl-1-pyrroline-N-oxide and 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide as spin traps for HO and SO4•−

          Graham S. Timmins, Ke Jian Liu, Etelvino Bechara … (1999)
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            Oxidative stress measurement by in vivo electron spin resonance spectroscopy in rats with streptozotocin-induced diabetes.

            T. Hashimoto, H Utsumi, H Nawata … (1998)
            Enhanced oxidative stress in diabetic patients may contribute to the pathogenesis of diabetic angiopathy. We have recently developed a method to determine the electron spin resonance (ESR, electron paramagnetic resonance; EPR) of reactive oxygen species and free radicals in vivo, using the nitroxide derivative, carbamoyl-PROXYL as a probe. In this study, diabetes was induced in Wistar rats by streptozotocin (STZ) injection (65 mg/kg, body weight, intravenously). Two, 4, and 8 weeks later, the animals received carbamoyl-PROXYL (300 nmol/g, intravenously), and ESR was measured at the upper abdominal level at a frequency of 300 MHz. The intensity of the carbamoyl-PROXYL ESR signal decreased gradually after the injection, and the spin clearance rate was determined over the first 5 min. At all time points, the spin clearance rate was significantly greater in the diabetic rats than in control rats. Moreover, the spin clearance rate in the diabetic rats was significantly correlated with urinary malondialdehyde (MDA) levels, which serve as a marker for lipid peroxidation. Daily treatment with 4 units neutral protamin Hagedorn (NPH) insulin for 4 weeks reduced the spin clearance rate in the diabetic rats. Simultaneous injection of carbamoyl-PROXYL and superoxide dismutase reduced the spin clearance rate in the diabetic rats in a dose-dependent manner. Injection of the antioxidant alpha-tocopherol (40 mg/kg, intraperitoneally) for 2 weeks restored the spin clearance rate in the diabetic rats without concomitant glycaemic restoration. These results suggest that a diabetic state enhances the generation of free radicals in vivo, and that both glycaemic control and antioxidant treatment can reduce this oxidative stress. Non-invasive in vivo ESR measurement may be useful for evaluating oxidative stress in diabetes.
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              In vivo imaging of oxidative stress in the kidney of diabetic mice and its normalization by angiotensin II type 1 receptor blocker.

              Toshiyo Sonta, Toyoshi Inoguchi, Shingo Matsumoto … (2005)
              This study was undertaken to evaluate oxidative stress in the kidney of diabetic mice by electron spin resonance (ESR) imaging technique. Oxidative stress in the kidney was evaluated as organ-specific reducing activity with the signal decay rates of carbamoyl-PROXYL probe using ESR imaging. The signal decay rates were significantly faster in corresponding image pixels of the kidneys of streptozotocin-induced diabetic mice than in those of controls. This technique further demonstrated that administration of angiotensin II type 1 receptor blocker (ARB), olmesartan (5 mg/kg), completely restored the signal decay rates in the diabetic kidneys to control values. In conclusion, this study provided for the first time the in vivo evidence for increased oxidative stress in the kidneys of diabetic mice and its normalization by ARB as evaluated by ESR imaging. This technique would be useful as a means of further elucidating the role of oxidative stress in diabetic nephropathy.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISBN: 978-3-8055-8074-8
                ISBN: 978-3-318-01315-3
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2006
                Publication date (Print): March 2006
                Publication date (Electronic): 10 March 2006
                Volume: 103
                Issue: 2
                Pages: c71-c76
                Affiliations
                Department of Nephrology, Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
                Article
                Publisher ID: 90612 Other ID: Nephron Clin Pract 2006;103:c71–c76
                DOI: 10.1159/000090612
                PubMed ID: 16543759
                SO-VID: 2ea7cbb0-5c1e-40fc-8479-d06a491ff2e4
                Copyright © © 2006 S. Karger AG, Basel
                License:

                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.

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                Figures: 4, References: 20, Pages: 1
                Categories
                Subject: Radiologic Imaging

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Electron paramagnetic resonance,Ischemia-reperfusion renal injury,Oxidative stress,Electron paramagnetic resonance imaging,Spin probe
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Electron paramagnetic resonance, Ischemia-reperfusion renal injury, Oxidative stress, Electron paramagnetic resonance imaging, Spin probe

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