ANTIOXIDANTS IN THERAPY AND PREVENTIVE MEDICINE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 257 THE IMMUNE RESPONSE TO VIRAL INFECTIONS Edited by B. A. Askonas, B. Moss, G. Torrigiani, and S. Gorini Volume 258 COPPER BIOAVAILABILITY AND METABOLISM Edited by Constance Kies Volume 259 RENAL EICOSANOIDS Edited by Michael J. Dunn, Carlo Patrono, and Giulio A. Cinotti Volume 260 NEW PERSPECTIVES IN HEMODIALYSIS, PERITONEAL DIALYSIS, ARTERIOVENOUS HEMOFILTRATION, AND PLASMAPHERESIS Edited by W. H. HOri and P. J. Schollmeyer Volume 261 CONTROL OF THE THYROID GLAND: Regulation of Its Normal Function and Growth Edited by Ragnar Ekholm, Leonard D. Kohn, and Seymour H. Wollman Volume 262 ANTIOXIDANT NUTRIENTS AND IMMUNE FUNCTIONS Edited by Adrianne Bendich, Marshall Phillips, and Robert P. Tengerdy Volume 263 RAPID METHODS IN CLINICAL MICROBIOLOGY: Present Status and Future Trends Edited by Bruce Kleger, Donald Jungkind, Eileen Hinks, and Linda A. Miller Volume 264 ANTIOXIDANTS IN THERAPY AND PREVENTIVE MEDICINE Edited by Ingrid Emerit, Lester Packer, and Christian Auclair Volume 265 MOLECULAR ASPECTS OF DEVELOPMENT AND AGING OF THE NERVOUS SYSTEM Edited by Jean M. Lauder, Alain Privat, Ezio Giacobini, Paola S. Timiras, and Antonia Vernadakis A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. ANTIOXIDANTS IN THERAPY AND PREVENTIVE MEDICINE Edited by Ingrid Emerit Centre National de la Recherche Scientifique and University of Paris Paris, France Lester Packer University of California, Berkeley Berkeley, California and Christian Auclair Institut Gustave-Roussy ViIlejuif, France PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Society for Free Radical Research Winter Meeting on Free Radicals in Medicine: Cur rent Status of Antioxidant Therapy (1988: Paris, France) Antioxidants in therapy and preventive medicine I edited by Ingrid Emerit, Lester Packer, and Christian Auclair. p. cm. -(Advances in experimental medicine and biology; v. 264) Proceedings of the Society for Free Radical Research Winter Meeting on Free Radicals in Medicine: Current Status of Antioxidant Therapy, held December 9-10, 1988, in Paris, France-T.p. verso. Includes bibliographical references. ISBN-13: 978-1-4684-5732-2 e-ISBN-13: 978-1-4684-5730-8 001: 10.1007/978-1-4684-5730-8 1. Antioxidants - Therapeutic use-Testing -Congresses. 2. Active oxygen Pathophysiology-Congresses. I. Emerit, Ingrid. II. Packer, Lester. III. Auclair, Christian. IV. Society for Free Radical Research. V. Title. VI. Series. [DNLM: 1. Antioxidants-therapeutic use-congresses. 2. Free Radicals-congresses. 3. Superoxide-adverse effects-congresses. 4. Superoxide Dismutase-therapeutic use-congresses. WDI AD559 v. 264 I QV 800 S678a 1988) RM666.A555S65 1988 615'.7-dc20 DNLM/DLC 89-70966 for Library of Congress CIP Proceedings of the Society for Free Radical Research Winter Meeting on Free Radicals in Medicine: Current Status of Antioxidant Therapy, held December 9-10, 1988, in Paris, France © 1990 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1990 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE Twenty years ago, the enzyme superoxide dismutase which uses the superoxide radical anion as its specific substrate was reported. With this discovery was born a new scientific field, in which oxygen, necessary for aerobi c 1i fe on thi s planet, had to be cons i dered also in terms of its toxicity and stresses. This stimulated the search for knowledge of active oxygen species in biology and medicine. Superoxide and other reactive oxygen species are now implicated in many disease processes. Major advances have been achieved during these past years with respect to free radical generation and mechanisms of free radical action in causing tissue injury. In parallel, the possibil ity of influencing free radical related disease processes by antioxidant treatment was studied in various in vitro and in vivo systems. This was the unique theme of a conference organized in Paris by the Society for Free Radical Research (December 9-10, 1988) which brought together experts from basic sciences and clinicians in order to evaluate the current status of antioxidant therapy. The conference emphasized fundamental processes in antioxidant action. Among the major topics were superoxide dismutase (SOD) and low molecular weight substances with such activity, called SOD mimics. Other antioxidant enzymes were also considered. Antioxidant vitamins, in particular vitamins E and C, other naturally occurri ng antioxidants and vari ous synthet i c antioxidants were included in the presentations as there is now a rapidly developing series of compounds with potentially interesting clinical applications. Clinical trials and results obtained in animal models were considered together with the use of antioxidant therapy in various diseases. Examples are ischemia-reperfusion injury, rheumatic, pulmonary, neuromuscular and ocular diseases, pancreatitis, cystic fibrosis and diabetes. Another important topic was the possibility to influence various dermatological disorders, photooxidative stress and cutaneous aging. Radiation and chemotherapy of cancer were discussed in terms of minimizing side effects by antioxidant therapy. Many reports of clinical trials were preliminary. There is a great need for controlled trials. Nevertheless, the overall impression at the conference and in these proceedings is optimistic for future developments. We gratefully acknowledge support for the conference which was provided by the following sponsors: Institut de Recherches Internationales Servier France Fondation IPSEN p.la Recherche lherapeutique France Henkel Corp. USA and Henkel KG FRG Nestle SA Switzerland Laboratoires Chauvin Blache France Laboratoires Sandoz France Nattermann GMBH FRG Laboratories Labcatal France Parfums Rochas Paris France v Lutsia Paris France Groupement des Enterprises Francaises dans la Lutte contre le Cancer Paris - Ile de France The Editors CONTENTS SUPEROXIDE DISMUTASE ExtraceLLuLar Superoxide Dismutase: Distribution in the Body and Therapeutic AppLications............................ 1 S. MarkLund and K. KarLsson Targeting SOD by Gene and Protein Engineering and Inhibition of Oxidative Stress in Various Diseases........... 5 M. Inoue and N. Watanabe The RoLe of Superoxide Dismutase (SOD) in Preventinq Postischemic SpinaL Cord Injury.............................. 13 K. Grabitz, E. Freye, R. Prior, R. KoLvenbach and W. Sandmann SOD in Rat ModeLs of Shock and Organ Failure....................... 17 H. RedL, C. Lieners, S. Bahrami, G. Schlag, I.P.T. van Bebber and R.J.A. Goris The Protective RoLe of Superoxide Dismutase During Activation of RibonucLeotide Reductase....................... ~9 M. Fontecave and P. Reichard Effect of Superoxide Dismutase on the Autoxidation of Hydroquinones Formed during DT-Diaphorase CataLysis and GLutathione NucLeophiLic Addition........................ 37 E. Cadenas and L. Ernster COPPER COMPLEXES AND OTHER SOD MIMICKS Superoxide Scavengers and SOD or SOD Mimicks....................... 45 G. Czapski and S. GoLdstein Reactivity of Active Centre AnaLogues of CU2Zn2 Superoxide Dismutase......................................... 51 U. Weser, R. MieseL and M. Linss SOD Mimicking Properties of Copper(II) CompLexes: HeaLth Side Effects.......................................... 59 G. LapLuye Radiation Recovery Agents: Cu(II), Mn(II), Zn(II) or Fe(III) 3,5-DiisopropyLsaLicyLate CompLexes FaciLitate Recovery from Ionizing Radiation Induced RadicaL Mediated Tissue Damage....................................... 69 J.J.R. Sorenson, L.S.F. Soderberg, M.L. Baker, J.B. Barnett, L.-W. Chang, H. SaLari and W.M. WiLLingham VII Effects of Glycyl-Histidyl-Lysyl Chelated Cu{ll) on Ferritin Dependent Lipid Peroxidation........................ 79 D.M. Miller, D. De Silva, L. Pickart and S.D. Aust SOD-Like Activity of 5-Membered Ring Nitroxide Spin Labels......... 85 A. Samuni, A. Min, C.M. Krishna, J.B. Mitchell and A. Russo ANTIOXIDANT VITAMINS Vitamin E in Biological Systems.................................... 93 L. Packer and S. Landvik The Role of Vitamine E in the Hepatotoxicity by Glutathione Depleting Agents................................. 105 A.F. Casini, E. Maellaro, B. Del Bello and M. Comporti Regulation of Lipid Peroxidation by Glutathione and Lipoic Acid: Involvement of Liver Microsomal Vitamin E free radical reductase............................. 111 A. Bast and G.R.M.M. Haenen Quenching of Singlet Oxygen by Tocopherols......................... 117 S. Kaiser, P. Di Mascio, M.E. Murphy and H. Sies Antioxidant Properties of Vitamin E and Membrane PermeabiLity in Human Fibroblast Cultures.................... 125 M. Conti, M. couturier, F. Lemonnier and A. Lemonnier Vitamin E and Tumor Growth......................................... 129 M. Gerber, S. Richardson, F. Favier and A. Crastes de Paulet Abnormal Susceptibility to Lipid Peroxidation of Plasma LDL and its Prevention by Alpha-Tocopherol during Experimental Cholestasis in the Rat.......................... 133 L.G. Alcindor, H. Antebi, M. Fadel-Khadra, M.C. Piot Y. Giudicelli and R. Nordmann The Role of Oxidative Modification and Antioxidants in LDL Metabolism and Atherosclerosis........................... 139 W. Jessup, R.T. Dean, C.V. de Whalley, S.M. Rankin, D.S. Leake Effects of Vitamin E Treatment in Cholestatic Childre~............. 143 F. Lemonnier, F. Alvarez, F. Babin, M. Couturier, D. Alagille Efficacy of Vitamin E as a Drug in Inflammatory Joint Diseases..................................................... 147 K.H. Schmidt and W. Bayer Vitamin E and Correlated Antioxidants: A y Radiolysis Study....... ••••••••••••••.•••....•••.....•.. ..•••.•.•....••. 151 D. Jore, M.N. Kaouadji and C. Ferradini Ascorbate: The Most Effective Antioxidant in Human Plasma.......... 155 B. Frei, R. Stocker, L. England and B.N. Ames VIII OTHER NATURAL AND SYNTHETIC ANTIOXIDANTS Radical Chemistry of Flavonoid Antioxidants........................ 165 W. Bors, W. Heller, C. Michel and M. Saran Scavenging Effects of Aspalathus Linealis (Rooibos Tea) on Active Oxygen Species..................................... 171 T. Yoshikawa, Y. Naito, H. Oyamada, S. Ueda, T. Tanigawa ~. Takemura, S. Sugino and M. Kondo Selenium and Oxidant Injury in Patients with Cystic Fibrosis....... 175 M.J. Richard, B. Aguilaniu, J. Arnaud, J.P. Gout and A. Favier Selenium and Glutathione Peroxidase Activity in Diploid Human Fibroblasts. Their Effects against H202 or UVB Induced Toxicity......................................... 179 M.J. Richard, P. Frappat, J. Arnaud, A. Favier Selenium Therapy in Down Syndrome. A Theory and a Clinical Trial............................................... 183 E. Antila, U.R. Nordberg, E.L. Syvaoja, T. Westermarck Protection by Seleno-Organlc Compound, Ebselen, against Acute Gastric Mucosal Injury Induced by Ischemia- Reperfusion in Rats.......................................... 187 S. Ueda, T. Yoshikawa, S. Takahashi, Y. Naito, H. Oyamada, T. Takemura, Y. Morita, T. Tanigawa, S. Sugino and M. Kondo Biological Activities and Clinical Potential of Ebselen............ 193 M.J. Parnham Glutathione Level in Mouse Brain after Testosterone Administration............................................... 199 F. Atroshi, L. Paulin, T. Paalanen and T. Westermarck Prostaglandins, Glutathione Metabolism and Lipid Peroxidation in Relation to Inflammation in Bovine Mastitis..................................................... 203 F. Atroshi, S. Sankari, A. Rizzo, T. Westermarck, J. Parantainen Sulfur Containing Compounds as Antioxidants........................ 209 P.M. Dansette, A. Sassi, C. Deschamps and D. Mansuy Zinc, a Redox-Inactive Metal Provides a Novel Approach for Protection against Metal-Mediated Free Radical Induced Injury: Study of Paraquat Toxicity in E.coli......... 217 M. Chevion, P. Korbashi, J. Katzhandler and P. Saltman Antioxidative Action of Zinc-Carnosine Compound Z-103.............. 223 T. Tanigawa, T. Yoshikawa, Y. Naito, T. Yoneta, S. Ueda, H. Oyamada, T. Takemura, Y. Morita, K. Tainaka, N. Yoshida, S. Sugino, M. Kondo High Molecular Weight Forms of Deferoxamine: Novel Therapeutic Agents for Treatment of Iron Mediated Tissue Injury.... •••• ••••• 229 B.E. Hedlund, P.E. Hallaway and J.R. Mahoney IX Oxygen Toxicity: RoLe of Hydrogen Peroxide and Iron................ 235 B.S. van Asbeck Antioxidant Properties of an Anti;schaemic Agent: Trimetazidine................................................ ~47 P. CLauser and C. Harpey Oxidative Damage in Chronic Heart FaiLure: Protection by CaptopriL through Free RadicaL Scavenging?............... 251 M. Chopra, J.M. Murray, J. McLay, A. Bridges and J.J.F. BeLch Free RadicaL Scavenging Capacity and Anti-InfLammatory Activity of CBS-113 A........................................ ~57 C. Bonne, G. Tissie, H.N. Trong, E. Latour and C. CoqueLet Mechanism, whereby Different Antioxidants and Lipoxy- genase Pathway Inhibitors Suppress IL2 Synthesis............. 261 J. Dornand and M. Gerber Reactive Oxygen Species ReLeased by Human BLood neutrophiLs from Piroxicam-Treated HeaLthy Subjects...................... 265 M. Damon, C. Chavis, C. Le Doucen, F. BLotman and A. Crastes de PauLet Antioxidative properties of met- and Leu-EnkephaLin................ 271 T. Marotti, V. Sverko and I. Hrsak PLateLet-Activating Factor AmpLifies Tumour Necrosis Factor-Induced Superoxide Generation by Human NeutrophiLs.................................................. 275 M. Paubert-Braquet, P. KoLtz, J. GuiLbaud, D. Hosford P. Braquet Comparison of Antioxidant and Prooxidant Activity of Various Synthetic Antioxidants............................... 283 R. KahL, S. Weinke and H. Kappus RADIATION AND CHEMOTHERAPY Antioxidant Effects in Radioprotection............................. 291 P. Bienvenu, F. ~erodin, M. Fantome and J.F. Kergonou NucLear GLutathione Transferases which Detoxify Irradiated DNA............................................... 301 B. Ketterer, G. Fraser and D.J. Meyer Urinary Biomarkers in Radiation Therapy of Cancer.................. 311 D.S. BergtoLd, C.D. Berg, M.G. Simic Redox Parameters Associated to Cytotoxic and Antitumor Activities in the Series of Antitumor Drugs ELLipticines and Derivatives................................. 317 C. AucLair Peroxidase Induced Metabolism and Lipid Peroxide Scavenging by Antitumor Agents............................... 323 P. KoLodziejczyk and J.W. Lown x