New comprehensive biochemistry vol 28 free radical damage and its control

FREE RADICAL DAMAGE AND ITS CONTROL New Comprehensive Biochemistry Volume 28 General Editors A NEUBERGER London L.L.M van DEENEN Uti-echt ELSEVIER Amsterdam London New York Tokyo Free Radical Damage and its Control Editors Catherine A Rice-Evans Free Radical Research Group, United Medical and Dental Schools, Guy’s & St Thomas’s Hospital, St Thomas’s Street, London, U K SEl9RT Roy H Burdon Department of Bioscience & Biotechnology, The Todd Centre, University of Strathclyde, Glasgow, Scotland, U K G4 ONR Amsterdam 1994 ELSEVIER London New York Tokyo Elsevier Science B.V P.O Box 21 1000 AE Amsterdam The Netherlands Library of Congress Cataloging-in-Publication Data Free radical damage and its control /editors Catherine A Rice -Evans Roy H Burdon p cni (New comprehensive biochernislry ; v 2x1 Includes hihliographical references and index ISBN 4 - X Y 16-x (alk paper). ISBN 0-444- XO303 -3 (series: il I I Free radicals (Chemistry) Pathophysiology Activeoxypen Antioxidants Rice-Evnns,Catherine 11 Burdon R H (Roy Hunter) 111 series IDNLM: I Free Radicals Reactiveoxygen Species WI NE372F v 2X 1994 / Q V 312 F852S 19941 3.Antioxidmts QD41S.N48 vol 28 [ nB I 701 574 19'2s dc20 lhIh.07'I I DNLMiDLC 93 - 40 IS4 for Library o f Congress CIP ISBN 444 897 16-X ISBN 4 80303-3 (series) 1994 Elsevier Science B.V All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the publisher, Elsevier Science B.V., Copyright and Permissions Department, P.O Box 52 I , I000 AM Amsterdam, The Netherlands No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, necgligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of the rapid advances in the medical sciences the publisher recommends that independent verification of diagnoses and drug dosages should be made S p c ~ i c i /wLqir/otionsfor m i d t w iu rlic USA - This publication has been registered with the Copyright Clearance Center Inc (CCC), Salem, Massachusetts Information can be obtained from the CCC about conditions under which photocopies of parts of this publication may be made in the USA All other copyright questions, including photocopying outside ofthe USA, should be referred to the publisher Printed on acid-free paper Printed in the Netherlands V Preface In this volume of New Comprehensive Biochemistry the international authorship has aimed to provide a comprehensive treatise on the chemical and biochemical consequences of damaging free radical reactions, the implications for the pathogenesis of disease and how this might be controlled endogenously and by radicalscavenging drugs The important developments in biochemistry presented here impinge not only on fundamental biology, but are also of primary concern to clinical medicine and human nutrition Free radicals are essential to a number of normal biochemical and physiological processes but are kept under control by the primary antioxidants, the cytoprotective enzymes, and the secondary antioxidants, such as the transition-metal and haem protein binders and the interceptors of propagating radical reactions Oxidative stress is said to arise when “the balance between oxidants and antioxidants is tipped in favour of the former” This may be influenced by exogenous agents of oxidative stress, radiation, trauma, drug activation, oxygen excess, for example, or by endogenous oxidative stress which is associated with many pathological states including chronic inflammatory disorders, cardiovascular disease, injury to the central nervous system, connective-tissue damage, etc These are some of the aspects we have selected to emphasise in this volume The approach of novel potentially therapeutic iron-chelating agents and antioxidants, including the lazaroids and the hydroxypyridinones is also reviewed The scene is set by comprehensive in-depth reports on the chemistry of free radical reactions involving iron and copper, the major transition metals involved in metalloproteins in living cells, and the biochemical constraints of their participation in oxidative stress The potential mode of action of reactive oxygen species in cell proliferation and the transmission of messages from the extracellular environment to the nucleus are also highlighted Recent research has focussed on the role of antioxidant nutrients in reducing the risk of developing coronary heart disease and cancer, the major killers in Western industrialised society Several epidemiological studies have reported in particular the relevance of a-tocopherol in the context of coronary heart disease and p-carotene in cancer, especially that of the lung The development of antioxidant drugs for the treatment of diseases associated with free radicals is a vibrant area of research but depends on the understanding of the mechanisms vi underlying the generation of excessive free radicals in vivo, the factors controlling their release and the site of their action In many disease states, the nature and original location of the radical species that amplify the primary damage are unknown, making the design and targeting of appropriate antioxidant drugs difficult Thus a detailed understanding of the processes leading to the radical-dependent pathology, as well as to the nature and sources of the toxic species, is crucial for the design of effective intervention strategies The individual chapters present up to date accounts of the current state of knowledge in these areas The editors warmly acknowledge all the contributing authors for participating in the production of this important text Catherine A Rice-Evans Roy H Burdon May 1993 vii List of contributors J.E Baker, 333 Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA M.S Baker, 301 Senior Lecture6 Department of Biological Sciences, University of Wollongong, NorthJield j Ave., Wollongong, NS W 2522, Australia D.R Blake, 361 InPammation Research Group, The London Hospital Medical College, University of London, Turner Street, London, UK E l 2AD R.H Burdon, 155 Department of Bioscience & Biotechnology, The Todd Centre, University of Strathclyde, Glasgow, Scotland, UK G4 ONR J Chaudiire, 25 Centre de Recherche BIOmTECH, Z.A des petits carreaux, avenue des coquelicots, 94385 Bonneuil-sur-Marne Cedex, France C.F Chignell, 319 Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA C.E Cooper, 67 Department of Paediatrics, University College London School of Medicine, The Rayne Institute, University Street, London, UK WCIE 6JJ A.T Diplock, 113 Free Radical Research Group, Division of Biochemistry, United Medical and Dental Schools of Guyk & St Thomas? Hospital, St Thomas Street, London, UK SEI 9RT P Duriez, 257 Dipartement d 'Etudes des Lipides et des Lipoprote'ines, SERLIA et U325 Inserm, rue du Prof Calmette, F59019 Lille Cedex, France J.C Fruchart, 257 Dipartement d 'Etudes des Lipides et des Lipoprotkines, SERLIA et U325 Inserm, rue du Pro$ Calmette, F59019 Lille Cedex, France E.D Hall, 217 Central Nervous System Diseases Research, The Upjohn Company, Kalamazoo, MI 49001, USA R.C Hider, 189 Department of Pharmacy, King j College London, University of London, Manresa Road, London, UK SW3 6LX Vlll J Joseph, 333 Biophysics Research Institute, Medical College o j Wisconsin, Milwaukee, WI 53226, USA B Kalyanaraman, 333 Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA E.A Konorev, 333 Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA W.H Koppenol, Departments of Chemistry and Biochemistry, Louisiana State University, Baton Rouge, LA 70803, USA R.P Mason, 19 Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA C.J Morris, 361 Injammation Research Group, The London Hospital Medical College, University of London, Turner Street, London, UK E l 2AD L Packer, 239 Department of Molecular and Cell Biology, University of Callfornia, Berkeley, CA 94720, USA B.J Parsons, 281 Multidisciplinary Research and Innovation Centre, North East Wales Institute, Deeside, Clwyd, UK CH5 4BR C.A Rice-Evans, 131 Reader in Biochemistry, Free Radical Research Group, United Medical and Dental Schools, G u y ) & St Thomas) Hospital, St Thomas Street, London, UK SEl 9RT S Singh, 189 Department of Pharmacy, King j College London, University of London, Manresa Road, London, UK SW3 6LX VR Winrow, 36 Inflammation Research Group, The London Hospital Medical College, University of London, Turner Street, London, UK E l 2AD PG Winyard, 361 Injammation Research Group, The London Hospital Medical College, University of London, Turner Street, London, UK E l 2AD M Zaidi, 361 Department of Cellular and Molecular Sciences, St George b Hospital Medical School, London, UK IX Contents Preface List of contributors PART I V vii Chemical and Biochemical Aspects Chapter Chemistry of iron and copper in radical reactions KH Koppenol Abbreviations Introduction Autoxidation reactions 2.1 Oxygen 2.2 Thermodynamics 2.3 Kinetics and mechanisms Fenton reactions 3.1, Introduction 3.2 Thermodynamics 3.3 Kinetics 3.4 Intermediates Speciation and effectiveness in promoting oxyradical d Acknowledgement References 11 12 13 13 18 20 20 Chapter Some chemical and biochemical constraints of oxidative stress in living cells Jean ChaudiBre 25 Abbreviations I The birth of the concept The basic properties of oxygen and th cept of oxygen activation The puzzling toxicity of superoxide Toxicity of hydroperoxides and their radical by-products 4.1 Hydrogen peroxide 4.2 Organic hydroperoxides 4.3 Sodium and calcium homeostasis 25 25 27 34 39 39 40 43 3 6 II 378 that TPA-activated cells contained increased levels of 8-OHdG (about 8-OHdG per 600 guanine bases in their DNA) compared with non-activated cells This increase was prevented by the presence of SOD during exposure of the cells to TPA This observation suggests that levels of 8-OHdG might be increased in the DNA of inflammatory cells from patients with various inflammatory diseases, making this DNA oxidation product a sensitive marker of cellular activation Recently, Perrett’s group [143] measured the rate of DNA unwinding (a measure of DNA strand breaks) in circulating mononuclear cells They found that the rate of DNA unwinding was significantly increased in RA, compared with normal control cells and osteoarthritis cells It appears that DNA damage is an early event in cells killed by oxygen radicals The capacity of endogenous intracellular antioxidants or of repair mechanisms for oxidative DNA damage might determine the susceptibility of different cell populations to either killing or mutation Lawley et al [ 1441 have demonstrated that circulating lymphocytes from patients with certain autoimmune diseases (e.g RA, systemic lupus erythematosus and Behcet’s syndrome) show increased sensitivity to the toxic effects of the alkylating agent N-methyl-N-nitrosourea compared with normal subjects and patients with other disorders The autoimmune disease cells are also relatively deficient in the DNA repair of 06-methylguanine Furthermore, lymphocytes from patients with a wide variety of autoimmune inflammatory conditions (e.g RA, systemic lupus erythematosus) have a higher susceptibility to Xirradiation [145] Such ionising radiation can damage DNA by production of ‘OH radicals formed in the aqueous surroundings of the target DNA Recently, we have found [ 1461 that the mean levels of 8-OHdG in lymphocyte and PMN DNA from normal healthy subjects were 68 and 118 mol of 8-OHdG per lo6 mol of deoxyguanosine, respectively However, the levels of 8-OHdG were elevated significantly in lymphocyte DNA from donors with inflammatory autoimmune diseases such as RA, systemic lupus erythematosus and vasculitis in comparison with healthy donors, with the exception of lymphocyte DNA from scleroderma patients We speculated that these differences might reflect a deficiency of DNA repair, rather than increased DNA damage In view of these findings, it is noteworthy that there is increasing evidence that oxygen radicals may play a part in mutation induced by a wide variety of agents [ 147,1481 We suggest that oxygen-radical-induced somatic mutation may play a role in the aetiology of certain autoimmune diseases, for example, by producing mutant cells displaying “altered self” antigenic determinants The increased incidence of malignancy found at sites of chronic inflammation may also be noted It has been suggested that the link may be oxygen radicals, since these are thought to be involved in both processes 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Parums, D.V, Brown, D.L and Mitchinson, M (1990) Arch Pathol Lab Med 114, 383-387 [I341 Loeb, L.A., James, E.A., Waltersdorph, A.M and Klebanoff, S.J (1988) Proc Natl Acad Sci U.S.A 85, 3918-3922 [135] Kasai, H., Crain, P.F., Kuchino, Y., Nishimura, S., Ootsuyama, A and Tanooka, H (1986) Carcinogenesis 7, 1849-1 85 [136] Kuchino, Y., Mori, F., Kasai, H., Inoue, H., Iwai, S., Miura, K., Ohtsuka, E and Nishimura, S (1987) Nature 327, 77-79 [137] Aruoma, O.I., Halliwell, B and Dizdaroglu, M (1989) J Biol Chem 264, 13024-13028 [I381 Cramp, W.A., George, A.M., Khan, H and Yatvin, M.B (1989) In: Free Radicals, Metal Ions and Biopolymers (Beaumont, P.C., Deeble, D.J., Parsons, B.J and Rice-Evans, C., Eds.), pp 127-141, Richelieu Press, London [139] Floyd, R.A., Watson, J.J., Harris, J., West, M and Wong, P.K (1986) Biochem Biophys Res Commun 137, 841-846 [I401 Richter, C., Park, J.-W and Ames, B.N (1988) Proc Natl Acad Sci U.S.A 85, 64654467 [141] Cundy, K.C., Kohen, R and Ames, B.N (1988) In: Oxygen Radicals in Biology and Medicine (Simic, M.G., Taylor, K.A., Ward, J.F and von Sonntag, C., Eds.), pp 479-482, Plenum Press, New York 11421 Bergtold, D.S., Simic, M.G., Alessio, H and Cutler, R.G (1988) In: Oxygen Radicals in Biology and Medicine (Simic, M.G., Taylor, K.A., Ward, J.F and von Sonntag, C , Eds.), pp 483489, Plenum Press, New York 11431 Bhusate, L.L., Herbert, K.E., Scott, D.L and Perrett, D (1992) Ann Rheum Dis 51, 8-12 11441 Lawley, PD., Topper, R., Denman, A.M., Hylton, W., Hill, I.D and Harris, G (1988) Ann Rheum Dis 47, 4 5 [145] Harris, G., Cramp, W.A., Edwards, J.C., George, A.M., Sabovljev, S.A., Hart, L., Hughes, G.R.V., Denman, A.M and Yatvin, M.B (1985) Int J Radiat Biol 47, 689-699 11461 Bashir, S., Harris, G., Denman, A.M., Blake, D.R and Winyard, P.G (1993) Ann Rheum Dis 52, 659-666 [147] Hsie, A.W., Recio, L., Katz, D.S., Lee, C.Q., Wagner, M and Schenley, R.L (1986) Proc Natl Acad Sci U.S.A., 83, 9616-9620 [148] Fiala, E.S., Conaway, C.C and Mathis, J.E (1989) Cancer Res 49, 5518-5522 [149] Schraufstatter, I.U., Hyslop, P.A., Jackson, J and Cochrane, C.C (1987) Int J Tiss Reac 9, 17-324 [ 1501 Trush, M.A., Seed, J.L and Kensler, T.W (1 985) Proc Natl Acad Sci U.S.A , 194-5 198 This Page Intentionally Left Blank 385 Subject Index absorption, 193 acetohydroxamic acid( I), 193 activated oxygen-derived molecules, 123 activator protein 1, 370 active oxygen species (AOS) as intercellular signals, I78 adenyl-cyclase, 162 adhesion molecules, 369 ADP-ribosylation, 1 adrenochrome, 365 adriamycin, 324, 368 affinity constants, 193 agranulocytosis, 200 albumin, 143, 157 aldehyde dehydrogenase, 162 aldehydes, 371 alkanals, 136 alkenals, 136 alkoxyl, 135, 138 alkoxyl radical, alkyl peroxyl free radicals, 103 alkyldioxyl radical, allopurinol, 167, 168, 363 alpha-1 antitrypsin, 172 a?-antiplasmin, 14, 373 a,-antiproteinax, 137 a1-antitrypsin, 372 a-tocopherol, 147, 149, 157-159, 162, 178, 240, 366 4-aminobenzoic acid, 325 aminocarboxylate, 199 21 -aminosteroid, 22 anaemia, 192 anchorin, 303 anion channels, 169 anti-inflammatory, 205, 365 anti-malarial, 21 anticancer agents, 195 antioxidant enzymes, 365 antioxidants, 113, 134, 259, 267, 321 antiproteases, 177 antiproteinases, 173 antithrombin 111, 373 apo B, 375 apotransfernn, 190 arachidonic acid, 77, 21 arrhythmogenic, 275 arthritis, 21 1, 309 articular cartilage, 303 ascorbate, 101, 102, 142, 144, 157, 240, 324 ascorbic acid, 366, 371, 372 asthma, 21 atheromatous disease, 125 atherosclerosis, 100, 139, 147, 257, 260, 375 atherosclerotic lesion, 142 atherosclerotic plaque, 145, 375 ATP, 363 ATP depletion, 10 autocrine, 174 autoimmunity, 376 autooxidation, 148 autoxidation, bacterial siderophore, 195 Behcet’s syndrome, 378 benzene, 101 p-carotene, 178, 366, 375 BHK-21, 165, 166, 172 BHK-21 cells, 166 bidentate, 193, 200 bidentate ligands, 194 bile, 196 biliary, 196 bilirubin, 371 biodistribution, 200 biological membranes, 195 biomolecules, 282 biopotency, 120 bleomycin, 367, 368 blood-barrier, 195 blood transfusions, 191 blood-brain barrier, 194, 198, 200 Bloom’s syndrome, 175 bone marrow, 190 bone-marrow transplantation, 192 bone resorption, 374 butylated hydroxytoluene, 147 C-fos, 163, 169, 171 c-fos products, 370 386 c j u n , 163, 171 c-jun products, 370 c-myc, 169, 370 c-ras, 370 caeruloplasmin, 142, 157, 365, 366, 376 calcium homeostasis, 43 carbon-radical, 83 carbon tetrachloride, 324 carbonyl, 138, 139 carboxylates, 193 carcinogenesis, 175 cardiac surgery, 333 carotenoids, 124, 125 cartilage, 373 catalase, 50, 72, 74, 77, 78, 83, 91, 94, 116, 158, 166, 167, 175, 176, 240, 323 catalase and glutathione peroxidase, 116 catalases, 68, 74, 75 catalysis, catalysis by divalent transition metal cation complexes, 126 catalytic copper, 376 catalytic iron, 366, 368 catalytic mechanisms of GSHPx, 118 catechol, 199 catecholates, 193 cation radical, 73, 76-78, 81, 82, 84, 88, 91, 94 cell differentiation, 162 cell division cycle, 155, 179, 208 cell growth, 161, 168 cell proliferation, 155, 159, 160, 163, 172, 180, 195 cell synchronisation, 10 cellular growth-fator receptors, 176 cellular reducing potential, 201 cellular release of active oxygen species, 164 cellular release of superoxide, 164 Ce(OOH)2, 310 CGD, 377 chain scission, 287 charge density, 193 chelatable iron, 195, 198 chelate, 193 chelation, 366 chemotaxis, 212 chemotherapeutic drugs, 368 chloroform, 101 chloroplast carotenoids, 125 chlorpormazine sulfoxide, 329 chlorpromazine, 325 chronic granulomatous disease, 362 chronic haemolysis, 193 cigarette smoking, 372 CNS injury, 217 CNS toxicity, 198 collagenase, 373 collagens, 303, 367, 368, 371, 372 colonic epithelial cells, 309 conductivity, 288 connective tissue, 281, 301, 302 control of secondary radicals, 19 coordinate bonds, 193 coordination, copper, 3, 78, 366, 376, 377 copper, zinc-superoxide dismutase (Cu, Zn-SOD), 177 copper complex, ~opper(II)-(3,5-diisopropylsalicylate)~ (CuDIPS), 166-168, 178 covalent binding, 321 cross-linked hyaluronic acids, 289 Cu2+, 365 Cu(II), 295 Cu(I1)-hyaluronic acid complex, 295 cutaneous antioxidants, 239 cutaneous pathology, 252 CdZn-containing enzyme, 14 cyclic AMP, 156, 157 cyclins, 157 cyclooxygenase, 101, 161, 211 cysteine switch, 12 cytochrome c, 103 cytochrome c oxidase, 67, 72 cytochrome oxidase, 68, 78, 79, 87, 98 cytochrome P-450, 68, 72, 78-80, 83, 100, 133 cytokine stimulus, 174 cytokines, 165, 369, 374 declomycin,, 325 dehydroascorbate, 122 deoxyhaemoglobin, 147 deoxymyoglobin, 143 depolymerisation, 288 dermis, 250 desferrioxamine, 144, 146, 179, 193, 202 desferrithiocin, 201 DFO, 195, 198 di-oxigenases, 82 dicarbonyls, 139 diethyldithiocarbamate, 166 differentiation, 163 387 3-(4,5-dimethylthiazol-2-yl)-2,5diphenylformazan bromide (MTT), 166 dioxygenase, 69, 82 diphenylene iodonium, 165 DMPO, 143 DNA, 376 DNA damage, 368 DNA repair, 368, 378 DNA synthesis, 156 docosahexaenoic acid, 161 dopamine, 207 double strand breaks, 368 doxorubicin, 209 drug-resistant, 1 DTPA(3), 199 early growth-regulated genes, 163, 169 early response genes, 371 EC SOD, 374 edema, 229 efficacy, 197 eicosapentaenoic acid, 160, 161 elastase, 372 elastase and cathepsin G, 15 electron paramagnetic resonance (EPR), 87, 320 electron spin resonance spectroscopy, 320, 338, 363 electron transport, 364 endocrine glands, 191 endoplasmic reticulum, 364 ENDOR, 87-89 endosome, 190 endothelial cells, 132, 146, 365, 374-376 endothelium-derived relaxing factor, 205, 344, 367 energetics, enzymatic mechanisms of protection, 114 epidermis, 250 epithelial cells, 190, 196 EPR, 88, 89, 93, 96, 97, 99, 102, 103, 143 erythrocyte, 142, 146-150 estradiol, 324 ethanol, 101 ethylenediamine tetra-acetic acid, 198 EXAFS, 85, 86 exercise, 142, 364, 373 extended X-ray absorption fine structure, see EXAFS extracellular protease inhibitors, 171 faeces, 196 Fanconi 's syndrome, 175 fatty streaks, 375, 316 Fe(I1)-chelates, 282 Fenton, 3, 31, 77, 102, 103, 324 ferric-hydroxide-phosphate, 191 ferric maltol, 12 ferritin, 142, 190, 191, 195 ferryl, 38, 67, 71, 72, 81-84, 86, 87, 91, 93-98, lOG103 ferryl haemoglobin, 102, 147, I50 ferryl myoglobin, 92, 94, 95, 97, 98, 103, 143, 144, 146 fibroblast proliferation, 368 fibroblasts, 132, 367, 371 fibroblasts, baby hamster kidney (BHK-21), 159, 163 fibroblasts, 208F, 167 fibromodulin, 303 fibronectin, 303, 308 fibrosis, 174, 367, 375 foam cells, 139, 375, 376 Fos, 156, 170, 171 free radicals, 26, 67, 72, 75, 87, 88, 97, 102, 155, 239,257,281, 301, 319 GI-phase, 155, 162 G-proteins, 156, 176 gamma irradiation, 368 gamma radiolysis, 288 GAPDH, 10 Gas chromatography-mass spectrometry, 377 gene transcription, 369 Gibbs energy, globus pallidus, 205 glomerulonephritis, 100 glutathione, 48, 127, 144, 240 glutathione peroxidase, 50, 117, 150, 158, 177, 240, 323 glutathione reductase, 240 glutathione-S-transferase family, 127 glutathione transferase, 159, 162 glycation, 139 glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 10 glycocalyx, 157, 172 glycosaminoglycans, 285 growth factor, 173, 174, 176 growth responses, 168, 180 guanylate cyclase, 133 388 Haber-Weiss reaction, 366 haem (or heme), 68, 71, 72, 74, 75, 77, 78, 80, 88, 90, 93, 97, 102, 322 haem oxygenase, 370, 371 haem protein (or hemoprotein), 134, 136, 141, 147, 150, 322 haemochromatosis, 193 haemoglobin, 73, 102, 141-146, 148-150, 189, 191, 192 haemolysate, 149 haemosiderin, 19 hairless mouse, 240 hamster (BHK-21), 169 haptoglobidhaemopexin, 143 HBED, 200 heart failure, 193 heat-shock proteins, 370 HeLa, 166-1 68 heme, see haem hemoprotein, see haem protein heparin, 365, 374 hepatocyte, 190, 323 hepatotoxic, 101 hexadentate ligands, 193, 194 high bioavailibility, 200 high-performance liquid chromatography, 377 higher molecular weight, 194 HNE, 163 horseradish peroxidase, 322 15-HPETE, 149, 151 human immunodeficiency virus-1, 369 human tumours, 161 hyalocytes, 28 hyaluronate, 306 hyaluronic acid, 28 hydoxypyridinones, 198 hydrogen dioxide, hydrogen peroxide, 3, 39, 102, 114, 141, 143, 149, 163, 164, 168, 169, 173, 174, 177, 180, 189, 198,295, 309, 322, 363 hydroperoxide, 39, 135, 147, 149, 150, 322 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 149 hydrophilic complex, 197 hydroxamate, 144, 199 hydroxy alkenals, 137 8-hydroxydeoxyguanosine (or 8-OHdG), 368, 77 hydroxyl radical, 3, 72, 100, 141, 143, 189, 194, 283, 366 hydroxylase, 82 hydroxylation, 368 hydroxylation of proline, 82 4-hydroxynonenal, 137, 138, 158, 162, 178 3-hydroxypyridin-4-ones, 200 hydroxypyridinones, 193 3-hydroxypyrones, 212 hydroxyurea, 208 Hylans, 289 hypervalent iron, 39 hypochlorous acid, 362, 373 hypoxanthine, 363 hypoxic reperfusion injury, 363 idiopathic haemochromatosis, 19 InB, 369 immune responses, 369 immunoglobulin G, 364 ineffective erythropoiesis, 197 inflammation, 101, 164, 205, 301, 361 inflammatory bowel disease, 174 inflammatory joint disease, 282, 375 initiation, 175 insulin, 169 interleukins, 369, 375 intestine, 196 intra- and intercellular messengers, 180 intra-articular pressures, 363 intracellular generation of superoxide, 166 intracellular signal transducers, 176 intracellularly generated superoxide, 167 iodoacetic acid, 10 ionising radiation, 365, 369, 371, 378 iron, 3, 67, 83, 86, 87, 93-95, 102, 189, 283, 306, 366-368, 371, 377 iron absorption, 189, 190 iron balance, 197 iron-catalysed Haber-Weiss reaction, 283 iron chelation, 179, 193, 202, 368 iron complex, 3, 196 iron excretion, 194 iron storage, 189 iron toxicity, 194 iron transport, 189, 190 iron(I1) sulphate, 212 irradiated skin, 239 ischaemia, 103, 219, 363 ischaemic tissue, 201 joint, 363 Jun, 156, 170, 171 389 Kachin-Beck Disease, 119 Keshan Disease, 119 kinetics, 9, 30 lactoperoxidase, 322, 323 leukotrienes, 160, 21 light-scattering, 290 link protein, 303 lipid hydroperoxides, 101, 136, 180, 246 lipid hydroperoxy radicals, 375 lipid peroxidation, 100-102, 113, 128, 135, 136, 138, 149, 159, 160, 178, 240, 257, 262, 321, 366-368, 371, 375 lipid peroxides, 180, 260 lipid peroxydation, 17 lipid peroxyl radicals, 366 lipophilic complex, 197 lipoproteins, 134, 143 lipoxygenase, 101 133, 134, 149, 150, 161, 195, 207 5-lipoxygenase, 198 liver, 191 liver cirrhosis, 101, 193 low-angle laser-light scattering, 287 low density lipoprotein (LDL), 102, 138, 145-147, 151, 257, 366, 375 low density lipoprotein PUFA, 119 lymphocytes, 132, 369, 374, 378 macrophages, 77, 146, 151, 374-376 magnetic circular dichroism (MCD), 93 magnetic susceptibility, 86 Maillard reaction, 139 malaria, 21 malondialdehyde (or malonyldialdehyde), 137, 138, 202, 240 malonyldialdehyde, see malondialdehyde manganese-superoxide dismutase (Mn-SOD), 177, 365 matrix metalloproteinases (MMPs), 12 MCD, 92 mercaptopropionyl glycine, 144 metalloenzyme inhibitors, 195 metalloenzymes, 207 metalloproteinases, 372 metastasis, 173 methaemoglobin (or methemoglobin), 148, 149, 323 methemoglobin, see methaemoglobin methionine sulphoxide, 372 methylprednisolone, 21 metmyoglobin, 90, 92, 103, 143, 323 minerals and nutrional deficiency, 19 minimal erythema1 dose, 245 mitochondria, 166 monocytes, 146 monooxygenase, 69, 82, 92 monosaccharides, 138, 139 monounsaturated fatty acids, 128 Mossbauer, 94, 95, 97 mouse keratinocytes, 179 MPO, 306 M P k o m p o u n d I1 complex, 307 muscle, 142, 143 mutagen, 377 mutation, 378 myeloperoxidase, 68, 72-74, 76, 77, 83, 98, 100, 132, 322, 362, 373 myocardial infarction, 142 myocardial injury, 202 myocardial ischemia, 333, 342 myocyte, 142 myoglobin, 83, 84, 86, 89, 94, 102, 141-143 N-acetyl cysteine, 144, 369 N-methyl-N-acetyl hydroxamate, 145 N-methyl-N-acyl hydroxamate, 146 N-methyl-N-acyl monohydroxamate, 144 N-methyl-N-hexanoyl hydroxamate, 144 NADPH oxidase, 131, 164, 165, 362 NADPH-cytochrome P-450 reductase, 325 Na+/K+-ATPase, 162 neoplastic cells, 177 neutrophil, 77, 100, 132, 322, 375 neutrophil oxidase, 100 NF-kappa B, see nuclear factor KB (NFKB) nilutamide, 324 nitric oxide, 133, 205, 367, 374 nitrite, 375 nitroblue tetrazolium, 166 nitrofurantoin, 324 NO-synthase, 367 non-transferrin-bound iron (NTBI), 19 nuclear factor KB (NFKB), 170, 369 nuclear magnetic resonance (NMR), 97 nuclear transcription factors, 176 8-OHdG, see 8-hydroxydeoxyguanosine optical spectroscopy, 90 organic NO donor, 344 organic peroxide, ornithine-decarboxylase,1 62 390 osteoblast, 374 osteoclast, 374 osteoporosis, 374 OX-LDL,257, 260-265, 273 oxidation of a-T, 120 oxidative damage, 364 oxidative modification, 375 oxidative phosphorylation, 20 oxidative stress, 321 oxidised low-density lipoproteins (Ox-LDL), see also Ox-LDL, 257, 260-265, 273 oxygen, 71, 78, 80, 82, 84, 98, 101, 189, 364 oxygen toxicity, 158 oxyhaemoglobin (or oxyhemoglobin), 147, 150, 323 oxyhemoglobin, see oxyhaemoglobin oxymyoglobin, 143 oxypurinol, 167, 168 P-450, 101 PAI-I, 314 PAI-2, 314 paraquat, 324 Parkinson’s disease, 207 pathogenicity, 195 penicillamine, 13 peroxidase, 68, 72-80, 83, 86-89, 91, 92, 94, 95, 97, 98, 100, 102 peroxidation, 158, 260 peroxide, 75, 90, 98, 103 peroxisomes, 16, 323 peroxy radicals, 290 peroxyl, 135, 138 peroxynitrite, 374 phagocyte, 134 phagocytic cells, 131 pharmacokinetics, 198 phenoxy radicals, 93, 99 phorbol ester, 164, 165 phospholipase, 138, 156, 162 phospholipase A*, 169 photoaging, 239 photoallergy, 326 photosensitivity, 326 photosensitization, 239 phototoxicity, 326 plasmin, 15 plasminogen activator-inhibitor, 373 platelet aggregation, 212 poly-ADP ribosylation, 171 polymorphonuclear leukocyte (PMN), 301, 362, 374 polysaccharides, 285 polyunsaturated fatty acid, 134-136, 147, 149, 160 porphyrin, 68, 71, 72, 75, 78, 82, 87, 88, 91, 93, 94 porphyrin cation radical, 96-98 porphyrin radicals, 93, 96, 98 probucol, 147 proline-hydroxylase, 69, 101 promotion, 175 prostaglandin, 77, 160, 161, 21 prostaglandin synthase, 68, 72, 77, 89, 91, 92, 101, 133, 134, 323 protease, 138, 376 protease inhibitor, 372 protease nexin I, 373 protein cross-linking, 102 protein free radicals, 67, 83, 102 protein-kinase, 157, 176 protein kinase C, 161, 165, 169-171, 173 proteoglycan aggregates, 303 proteoglycans, 285, 303, 307 proteolysis, 374 protooncogene, 156, 176, 369 protoporphyrin, 325 psoriasis, 1 pulmonary emphysema, 372 pulmonary fibrosis, 101 pulse radiolysis, 287 radiation, 282 rat (208F) fibroblasts, 163, 169 Raynaud’s phenomenon, 368 red blood cells, 192 redox cycling, 189 redox potentials, 72, 76-78, 100, 170 redox regulatory paradigm, 170 reduction potential, relative molecular mass, 17 released superoxide, 173 removal of lipid hydroperoxides, 126 renal damage, 142 reperfusion, 103, 142, 201, 363 reperfusion injury, 103, 143, 195, 333 resonance Raman spectroscopy, 98, 99 respiratory burst, 164, 362 reticulocytes, 190 reticuloendothelial cells, 195 rheumatoid arthritis, 101, 361, 372 39 rheumatoid joint, 142 rhodotorulic acid, 199 ribonucleotide reductase, 77, M , 87, 89, 96, 99, 133, 179, 195, 198, 200,207, 208 S-phase, 155, 179 S-thiolation, 54 scavenger receptors, 147, 264, 270, 375 SchifPbase, 137, 140 scleroderma, 368, 378 second messengers, 367 selenium, 50, 157, 178 selenoenzyme phospholipid hydroperoxide GSHPx, 127 semidehydroascorbate, I22 serpins, 314, 372 serum deprivation, 159 shock proteins, 370 sickle-cell anaemia, 195 siderophores, 197 signal transduction, 44, 161 simple diffusion, 195 single strand breaks, 368 singlet oxygen, 100, 101, 125, 327 skin, 239 skin cancer, 239 small intestine, 190 smooth muscle cells, 132, 146 sodium hyaluronate, 28 somatic mutation, 378 spectroscopic methods, 67 spin trap, 90, 103, 143, 327, 338, 342, 363, 74 splenectomized patients, 197 Streptomyces antibioricus, 201 stress proteins, 370 stromelysin, 373 structure, 120 substantia nigra, 205 sugar diabetes, 193 superoxide, 34, 131, 141, 146, 148, 158, 163, 168, 169, 177, 180, 189 superoxide dismutase, 49, 114, 166, 167, 175, 176,201,240, 365 superoxide radical, 114, 142, 180, 282 superoxide release, 165 synovial fluid, 281, 307, 372 systemic lupus erythematosus, 378 t-butyl hydroperoxide, 149 t-butyl hydroxide, 150 thalassaemia, 192 thalassaemia major, 195 thiol, 150 thiyl radical, 127 thrombospondin, 303 thymine glycols, 175 thyroxine, 323 TPA (12-0-tetradecanoy phorbol-13 acetate), 169, 170 transcription factors, 173, 369, 372 transferrin, 142, 190 transforming growth factor beta, 372 transfusion cycle, 197 transfusion requirements, 197 transition metals, 70, 87, 90 tridentate, 201 tryptophan, 68, 75, 84, 89, 94, 97, 102 tryptophan radical, 92 tumour formation, 175 tumour necrosis factor alpha, 324, 325, 369 tumour progression, 177 tumour promotion, 164, 176 tyrosine, 68, 72, 75, 77, 78, 80-82, 84, 88, 89, 91, 93, 97, 99 tyrosine hydroxylase, 207 tyrosine-peroxyl radical, 143 tyrosine-phenoxyl radical, 143 tyrosine phosphatase, 371 tyrosine radical, 92 U-78517F, 232 U-74006F (tirilazad mesylate), 22 ubiquinol, 240 ubiquinone (coenzyme Q), 126, 240 ultraviolet (UV) light, 239 unscheduled DNA synthesis, 368 uric acid, 128, 324 urine, I96 vasculitis, 378 vasoconstriction, 273 vasodilation, 367 vasodilatory effect, 343 venesection, 193 vitamin C (ascorbic acid), 47, 122 vitamin E (a-tocopherol), 46, 120, 259, 267, 366, 375 vitamin E antioxidant activity of a food, 120 vitamin E deficiency, 121 vitamin E deficiency in animals, 12 vitamin E deficiency in humans, 122 sT Wilson’s disease, 13 X-ray crystallography, 83 xanthine, 363 xanthine dehydrogenase, 362 xanthine oxidase, 131, 363 xanthine oxidase inhibitors, 168 Xeroderma pigmentosum, 175 .. .FREE RADICAL DAMAGE AND ITS CONTROL New Comprehensive Biochemistry Volume 28 General Editors A NEUBERGER London L.L.M van DEENEN Uti-echt ELSEVIER Amsterdam London New York Tokyo Free Radical. .. acid -free paper Printed in the Netherlands V Preface In this volume of New Comprehensive Biochemistry the international authorship has aimed to provide a comprehensive treatise on the chemical and. .. 374 375 376 379 370 PART I Chemical and Biochemical Aspects This Page Intentionally Left Blank C.A Rice-Evans and R.H Burdon (Eds.), Free Radical Damage and its Control 1994 Elsevier Science B.V