Site of Methylguanidine Production and Factors That Influence Production Levels

Abstract

The site of methylguanidine (MG) production in the kidney was investigated using animal models of renal disease and cultured renal epithelial cells. In rats with proximal tubular injury induced by adenine, the blood and urinary levels of MG increased as the severity of injury increased. In contrast, in cases of glomerular injury, there were no such changes in MG levels. Thus, it was apparent that proximal tubular injury served to promote MG production. In addition, a marked increase was observed in the intensities of bands attributable to 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH in the electron spin resonance spectrum of the kidney in the rats given adenine. In these rats, the activity of the radical-scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase was decreased. This suggests that the formation of excessive radicals and deterioration of defense mechanisms that contribute to the development of oxidative stress underlie the enhanced MG production. The experiments using cultured cells revealed that an oxide of adenine, 2,8-dihydroxyadenine (DHOA), directly induced renal tubular injury. These findings indicate that the accumulation of creatinine due to DHOA, combined with oxidative stress, resulted in increased MG production.

Journal

Journal ID (publisher-id): NEF

Journal ID (nlm-ta): Nephron

Journal ID (doi): 10.1159/issn.1660-8151

Title: Nephron

Publisher: S. Karger AG

ISSN (Print): 1660-8151

ISSN (Electronic): 2235-3186

Publication date Subscription-year: 2002

Publication date (Print): October 2002

Publication date (Electronic): 02 September 2002

Volume: 92

Issue: 2

Pages: 356-362

Affiliations

^aInstitute of Natural Medicine, ^bFaculty of Medicine, and ^cFaculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan

Article

Publisher ID: 63301 Other ID: Nephron 2002;92:356–362

DOI: 10.1159/000063301

PubMed ID: 12218314

Copyright statement: © 2002 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.

Page count

Figures: 2, Tables: 4, References: 51, Pages: 7

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Categories

Subject: Original Paper