Biology of Copper Complexes Experimental Biology and Medicine Biology of Copper Complexes, edited by John R. J. Sorenson, 1987 Epstein-Barr Virus and Human Disease, edited by P. H. Levine, D. V. Ablashi, M. Nonoyama, G. R. Pearson, and R. Glaser, 1987 Methods of Protein Sequence Analysis • 1986, edited by Kenneth A. Walsh, 1987 Regulation of Immune Gene Expression, edited by Marc Feldmann and Andrew McMichael, 1986 Biological Methylation and Drug Design, edited by Ronald T. Borchardt, Cyrus R. Creveling, and Per Magne Ueland, 1986 Retroviruses and Human Pathology, edited by Robert C. Gallo, Dominique Stehelin, and Oliviero E. Varnier, 1985 Directed Drug Delivery, edited by Ronald T. Borchardt, Arnold Repta, and Valentino Stella, 1985 Immune Regulation, edited by Marc Feldmann and N. A. Mitchison, 1985 Human T Cell Clones, edited by Marc Feldmann, Jonathan R. Lamb, and James N. Woody, 1985 Inositol and Phosphoinositides, edited by John E. Bleasdale, Joseph Eichberg, and George Hauser, 1985 Growth, Cancer, and the Cell Cycle, edited by Philip Skehan and Susan J. Friedman, 1984 Ir Genes, edited by Carl W. Pierce, Susan E. Cullen, Judith A. Kapp, Benjamin D. Schwartz, and Donald C. Shreffler, 1983 Methods in Protein Sequence Analysis, edited by Marshall Elzinga, 1982 Inflammatory Diseases and Copper, edited by John R. J. Sorenson, 1982 Membrane Fluidity, edited by Moms Kates and Arnis Kuksis, 1980 Biology of Copper Complexes Edited by John R. J. Sorenson University of Arkansas for Medical Sciences, Little Rock, Arkansas Humana Press • Clifton, New Jersey © Copyright 1987 by The Humana Press Inc. Softcover reprint of the hardcover 1s t edition 1987 Crescent Manor PO Box 2148 Clifton, NJ 07015 All rights of any nature whatsoever reserved. No part of this book may be reproduced, stored in a retrieval sytem, or transmitted in any form or by any means, including electronic, mechanical, photocopying, microfilming, recording, computer database entry, or networking, or in any other manner whatsoever without written permission from the publisher. Library of Congress Cataloging-in-Publication Data: Biology of copper complexes. (Experimental biology and medicine) Based on a symposium held in 1986. Includes index. 1. Copper-Physiological effect-Congresses. 2. Coordination compounds-Physiological effect-Congresses. 3. Copper-Metabolism-Congresses. 4. Coordination compounds-Metabolism-Congresses. 5. Copper-Therapeutic use-Congresses. 6. Coordination compounds-Therapeutic use-Congresses. I. Sorenson, John R. J. II. Series: Experimental biology and medicine (Clifton, NJ) [DNLM: 1. Copper-rnetabolism-congresses. 2. Copper-therapeutic use-congresses OU 1308614421986] OP 535.C9857 1987 612'.01524 87-17047 ISBN-13: 978-1-4612-8937-1 e-ISBN-13: 978-1-4612-4584-1 001:10.1007/978-1-4612-4584-1 Preface In 1928, it was discovered that copper was essential for normal human metabolism. Ten years later, 1938, it was observed that patients with rheumatoid arthritis had a higher than normal serum copper concentration, which returned to normal wi th remission of this disease. Thirteen years later, it was found that copper complexes were effective in treating arthritic diseaseS. The first report that copper complexes had antiinflammatory activity in an animal model of in flammation appeared twenty-two years after the discovery of essen tiality. In 1976, it was suggested that the active forms of the anti arthritic drugs are their copper complexes formed in vivo. This suggestion was confirmed and extended in the interim with over 1000 recent publications, and many of these were addressed in the proceed ings of our first symposium, published in 1982. The present symposium was organized to present new normal physiological, nutritional, and biochemical aspects of essential metal loelement metabolism as well as variations in metabolism associated with disease states. In addition new data concerning antimicrobial, antiinflammatory, antiulcer, anticancer, anticarcinogenic, analgesic, and radioprotectant activities of copper complexes were presented. These activities are consistent with the notion that they represent the facilitation of normal copper-dependent metabolic processes in dis ease states. The presentations and interactive discussions that fol lowed are contained in these proceedings. John R. J. Sorenson Dedication These proceedings are dedicated to those who made this truly memorable scientific and social Arkansas experience possible. They include: those whose persistent pioneering essential-metalloelement research efforts now provide important background information in support of new and exciting approaches to the understanding and treatment of chronic diseases; those who persist in providing new knowledge in these areas; Dr. Harry P. Ward, Chancellor of the University of Arkansas for Medical Sciences, and Dr. L. D. Milne, Dean of the College of Pharmacy, for the academic environment they provide and their personal and financial support; the sponsors, International Copper Research Association Arkansas Catfish Farmers Association Arkansas Forestry Association Arkansas Poultry Federation Arkansas Rice Festival Coca-Cola Bottling Company of Arkansas Dean Foods Mr. Floyd C. Villines, Little Rock City Director Kellogg Company Little Rock Convention Center Little Rock Regional Airport Mericon Industries, Incorporated Post Winery Silbernagel Company, Incorporated Skaggs Alpha-Beta Stores Smith Whetstones, Inc. and the participants for their persistent efforts and support in organ izing this meeting, as well as their free exchange of knowledge. Special thanks are also due to Mrs. Stacie A. Hronas for manu script corrections and retyping as well as transcribing and inserting recorded proceeding discussions, Mrs. Catherine M. Vaughan for her assistance in these proceedings, and Mrs. Mary Vick for her efforts in premeeting organization and coordinating activities during the meet ing. John R. J. Sorenson Contents Physiologic Aspects of Copper Complexes Session Chairperson: Peter Lipsky 3 A Physiological Basis for Pharmacological Activities of Copper Complexes: An Hypothesis, John R. J. Sorenson 17 Regulation of Ceruloplasmin Synthesis by Retinoic Acid and Interleukin-l, Robert J. Cousins and Ellen F. Barber 31 Role of Ceruloplasmin in Copper Transport, Edward D. Harris 43 Copper and the Regulation of Superoxide Dismutase Activ ity in Aortic Tissue, Charles T. Dameron and Edward D. Harris Biochemical Aspects of Copper Complexes Session Chairperson: Edward D. Harris 59 Influence of Diet and Inflammation on Serum Copper Enzymes, Robert A. DiSilvestro 67 Copper and Connective Tissue: The Mechanism of Lysyl Oxi dase, Frederick T. Greenaway and Coleen Young O'Gara 81 Copper-A Modulator of Peptide Release in the Brain, Ayalla Barnea 95 Copper-Dependent a-Amidations in the Synthesis of Neuroendocrine Peptide Hormones, Thomas R. Gibson and Christopher C. Glembotski 108 General Discussion vii viii Contents Copper Complexes in Essential Metalloelement Nutriture and Disease States Session Chairperson: Robert J. Cousins 115 Indices for Assessing Copper Nutriture in Animals and Humans, J. Cecil Smith, Jr. 127 Dietary Simple Sugars Increase the Severity of Copper Deficiency in Experimental Animals, Meira Fields 141 Hypertension Induced Alterations in Copper and Zinc Metabolism: A Link to Vascular Disease? Carl L. Keen, Michael S. Clegg, Fay Ferrell, Glenn C. Hunter, and Michael A. Dubick 155 Manifestations of Copper Deficiency in Dairy Cattle, Alfred W. Anderson 165 Observations on Biological Effects of Low Dietary Copper in Nebraska Beef Cattle, Jerre L. Johnson. N. R. Schneider, A. R. Doster, M. P. Carlson, and H. W. Leipold 175 Cuprous Sebacate Treatment in Menkes' Disease, Darryl M. Williams, John R. Clement, F. Scott Kennedy, and Harold Chen Biological Aspects of Copper and Iron in Inflammation Session Chairperson: Carl L. Keen 187 Role of Neutrophils in Inflammatory Tissue Injury, Edwin L. Thomas 201 Effect of Cu-DIPS on Ischemia-Reperfusion Injury, Lucrecia A. Hernandez, Matthew B. Grisham, and D. Neil Granger 215 Modulation of Lymphocyte Function by Copper and Thiols, Peter E. Lipsky Contents ix 229 Copper Regulation of Macrophage Eicosanoid and Cyclic Amp Synthesis, Graham R. Elliot, M. J. P. Adolfs, M. van Batenburg, and Ivan L. Bonta Antiinflammatory Activities of Copper Complexes Session Chairperson: Dean P. Loven 243 Antiinflammatory and Antiulcer Activities of Non-Steroidal Antiinflammatory Agent Copper Complexes, John R. J. Sorenson 259 Comparative Pharmacokinetics of Salicylic Acid and Cop per-Salicylate in Rats, Bhasker V. Shetty and Srikumaran Melethil 273 Iamin: A Human Growth Factor with Multiple Wound Healing Properties, Loren Pickart 287 Peroxide Scavenging by Cu(II) Sulfate and Cu(II) (3,5-Diiso propylsalicylate)2' Gregory A. Reed and Cherukury Madhu Analgesic and Antimicrobial Activities of Copper Complexes Session Chairperson: Ayalla Barnea 301 Copper Complexes Have Potent Analgesic Activity and They May Activate Opioid Receptors, Shigeru Okuyama, Sanae Hashimoto, Hironaka Aihara, William M. Willingham, and John R. J. Sorenson 315 Peptides and Opiates in Copper Deficiency, Sam J. Bhathena and Lillian Recant 329 Mechanism of the Antimycoplasmal Activity of 2,2' Bipyridyl Copper Complexes, H. van der Goot, H. T. Smit, H. -D. Gaisser, and H. Timmerman 343 Copper (I)-Nicotinic Acid Complex: An Immunopotentiator in Chickens Vaccinated Against Newcastle Disease, S. A. Musa, A. H. Hafez, A. Y. Nassar, and M. A. Gohar 351 General Discussion Anticancer Activities of Copper Complexes and Iron Chela tors Session Chairperson: Miera Fields 361 Anticancer Effects of Cu(II) (3, 5-Diisopropylsalicylate)2 in Mice Inoculated Intramuscularly with Ehrlich Ascites Carci noma Cells, Scott L. Kasemeier, Hamid Salari, and John R. J. Sorenson 371 Effect of Cu(II)(3,5-DIPS)2 on the Solid Ehrlich Tumor Growth in Mice: A Pathological Study, Doris Torregrosa, Louis W. Chang, Aubrey Hough, Jr., Scott L. Kasemeier, and John R. J. Sorenson 387 Copper and Copper Enzymes in the Development and Treatment of Cancer, Dean P. Loven 399 Catechol amide Iron Chelators: Antiproliferative Activity on Human Pathogens and Neoplasm, Gary T. Elliott Anticarcinogenic and Radioprotectant Activities of Copper Complexes Session Chairperson: Loren Pickart 413 Effects of Copper Complexes on Multistage Carcinogenesis, P. A. Egner, B. G. Taffe, and T. W. Kensler 425 Modulation of Benzopyrene Dependent Mutagenesis and Xanthine Oxidase Activity by Copper Complexes, John J. Reiners, Jr.