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      The Inhibition of Bovine Lens Aldose Reductase by Clinoril, Its Absorption into the Human Red Cell and Its Effect on Human Red Cell Aldose Reductase Activity

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          Abstract

          The protein aldose reductase has been implicated in cataract in diabetes and galactosaemia. Recently it has been suggested that a number of non-steroidal anti-inflammatory agents have inhibitory activity against aldose reductase activity, and therefore might be used to prevent diabetic complications including cataract. Steady state kinetic experiments show that Clinoril® (Sulindac sulphoxide) acts as a non-competitive inhibitor of NADPH oxidation with purified bovine lens aldose reductase, with an action that may involve binding to more than one site on the protein. As a preliminary to studying the effect on human lens and cataract, a double-masked, placebo-controlled study using random allocation into parallel groups was conducted on 20 volunteers to determine the penetration of Clinoril (Sulindac) and its metabolites into normal human red cells, and the effect of the drug on red cell NADPH-oxidising activity. It was found that while Clinoril, the sulphoxide form of the drug, and its metabolites the sulphone and the sulphide could be detected in the appropriate plasma samples (up to 36 μg of the sulphone / ml of plasma), very little could be detected in the red cells. There was no significant effect on red cell NADPH-oxidising activity.

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          Author and article information

          Journal
          ORE
          Ophthalmic Res
          10.1159/issn.0030-3747
          Ophthalmic Research
          S. Karger AG
          0030-3747
          1423-0259
          1985
          1985
          04 December 2009
          : 17
          : 2
          : 85-89
          Affiliations
          Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK
          Article
          265355 Ophthalmic Res 1985;17:85–89
          10.1159/000265355
          3920599
          6022ade7-6792-413c-be07-2996395e04b3
          © 1985 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.

          History
          : 14 February 1984
          : 11 May 1984
          Page count
          Pages: 5
          Categories
          Original Paper

          Vision sciences,Ophthalmology & Optometry,Pathology
          Cataract,Diabetes,Lens,Aldose reductase,Sulindac,Clinoril,Red Cell

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