Free radicals in biology and medicine:
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Oxford [u.a.]
Oxford Univ. Press
1999
|
| Ausgabe: | 3. ed. |
| Schriftenreihe: | Oxford science publications
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XXXI, 936 S. Ill., graph. Darst. |
| ISBN: | 0198500459 0198500440 |
Internformat
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| 245 | 1 | 0 | |a Free radicals in biology and medicine |c Barry Halliwell and John M. C. Gutteridge |
| 250 | |a 3. ed. | ||
| 264 | 1 | |a Oxford [u.a.] |b Oxford Univ. Press |c 1999 | |
| 300 | |a XXXI, 936 S. |b Ill., graph. Darst. | ||
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Datensatz im Suchindex
| _version_ | 1804126758619840512 |
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| adam_text | Contents
Plate section falls between pages 128 and 129
List of abbreviations xxix
1 Oxygen is a toxic gas—an introduction to oxygen
toxicity and reactive oxygen species 1
1.1 The history of oxygen: a major air pollutant 1
1.2 Oxygen today 4
1.2.1 Oxygen in water and organic solvents 4
1.3 Oxygen and anaerobes 4
1.3.1 Why does oxygen injure anaerobes? 6
1.4 Oxygen and aerobes 7
1.4.1 Oxygen transport in mammals 7
1.4.2 Oxygen sensing 8
1.4.3 Mitochondrial electron transport 8
1.4.4 Bacterial electron transport chains 9
1.5 Oxidases and oxygenases in aerobes 13
1.5.1 Cytochromes P450 14
1.6 Oxygen toxicity in aerobes 17
1.6.1 Oxygen toxicity in bacteria and plants 17
1.6.2 Oxygen toxicity in humans and other animals 18
1.6.3 Retinopathy of prematurity 20
1.6.4 Factors affecting oxygen toxicity 21
1.7 What causes the toxic effects of oxygen? 22
1.8 What is a free radical? 22
1.9 Oxygen and its derivatives 24
1.9.1 Singlet oxygen 25
1.9.2 Superoxide radical 26
1.9.3 Ozone 26
1.10 Questions of terminology: oxygen derived species,
reactive oxygen species and oxidants 27
1.11 Sources of superoxide in aerobes 27
1.11.1 Enzymes 28
1.11.2 Auto oxidation reactions 28
1.11.3 Haem proteins 30
1.11.4 Mitochondrial electron transport 31
1.11.5 Bacterial superoxide production 32
1.11.6 Endoplasmic reticulum 32
1.11.7 The nucleus 33
1.11.8 Quantification 33
xiv Contents
3.16.6 Why do plants have so much peroxidase? 168
3.16.7 Chloroperoxidase and bromoperoxidase 169
3.16.8 Ascorbate peroxidase 169
3.16.9 Peroxidase mimics 1 70
3.17 Antioxidant defence enzymes: co operation 170
3.17.1 The need for co operation 170
3.17.2 Down s syndrome 171
3.18 Antioxidant defence: sequestration of metal ions 172
3.18.1 Iron metabolism 172
3.18.2 Copper metabolism 176
3.18.3 Haem proteins: potential pro oxidants 177
3.18.4 Evidence that metal ion sequestration is important 178
3.19 Metal ion sequestration in different environments 184
3.19.1 Intracellular requirements 184
3.19.2 Metallothioneins 184
3.19.3 Phytochelatins 186
3.19.4 The extracellular environment 186
3.20 Haem oxygenase 189
3.21 Antioxidant protection by low molecular mass agents:
compounds synthesized in vivo 191
3.21.1 Bilirubm 191
3.21.2 a Keto acids 192
3.21.3 Sex hormones 192
3.21.4 Melatomn 192
3.21.5 Lipoic acid 194
3.21.6 Coenzyme Q 194
3.21.7 Uric acid 195
3.21.8 Histidine containing dipeptides 198
3.21.9 Melanins 198
3.22 Antioxidant protection by low molecular mass agents:
compounds derived from the diet 200
3.22.1 Ascorbic acid (vitamin C) 200
3.22.2 Ascorbate as an antioxidant in vitro 202
3.22.3 Is ascorbate an antioxidant in vivo? 203
3.22.4 Recycling of ascorbate 205
3.22.5 Pro oxidant effects of ascorbate 206
3.22.6 Ascorbate and iron overload disease 208
3.22.7 Vitamin E 208
3.22.8 Chemistry of vitamin E 209
3.22.9 Recycling of a tocopheryl radicals 215
3.22.10 Pro oxidant effects of a tocopherol 216
3.22.11 Processing of dietary vitamin E 216
3.22.12 Evidence for an antioxidant effect of
oe tocopherol in vivo 217
3.23 Carotenoids: important biological antioxidants? 220
3.23.1 Carotenoid chemistry 220
Contents xv
3.23.2 Metabolic roles of carotenoids 222
3.23.3 Carotenoids as antioxidants 223
3.24 Plant phenols 225
3.24.1 Phenols in the diet 225
3.24.2 Are plant phenols antioxidants in vivo ? 229
3.24.3 Herbal medicines 230
References 231
Notes 245
4 Oxidative stress: adaptation, damage, repair and death 246
4.1 Introduction 246
4.2 Consequences of oxidative stress: adaptation, damage
or stimulation? 246
4.2.1 Adaptation 247
4.2.2 Cell injury 249
4.2.3 Changes in cell behaviour 250
4.3 Consequences of oxidative stress: cell death 251
4.4 Oxidative stress and calcium 253
4.4.1 Cell calcium metabolism 253
4.4.2 Dysregulation by oxidative stress 254
4.4.3 The mitochondrial permeability transition 256
4.5 Oxidative stress and transition metals 257
4.5.1 Iron 257
4.5.2 Evidence for dysregulation of iron 257
4.5.3 Copper 262
4.6 Mechanisms of damage to cellular targets by oxidative
stress: DNA 262
4.6.1 DNA and chromatin structure 264
4.6.2 DNA cleavage and replication 266
4.6.3 Telomeres 267
4.6.4 Damage to DNA by ROS and RNS 267
4.6.5 Damage to mitochondrial and chloroplast DNA 273
4.6.6 Why does hydrogen peroxide lead to DNA damage? 274
4.6.7 Use of iron and hydrogen peroxide for DNA
footpnnting 276
4.6.8 Histidine as an extracellular pro oxidant for
DNA damage 276
4.7 Consequences of damage to DNA by ROS/RNS:
mutation 277
4.7.1 Mutagenicity ot oxidative base damage 27S
4.8 Consequences of damage to DNA by ROS/RNS:
DNA repair 278
4.8.1 Sanitization of the nucleotide pool 280
4.8.2 Repair of pyrimidme dimers 280
4.8.3 Excision repair 281
4.8.4 Repair of 8 hydroxyguanine 282
xvi Contents
4.8.5 Repair of double strand breaks and mitochondrial
repair 282
4.8.6 Evidence that DNA repair is important 282
4.9 Mechanisms of damage to cellular targets by oxidative
stress: lipid peroxidation 284
4.9.1 A history of peroxidation: from oils to textiles 284
4.9.2 Targets of attack: membrane lipids 285
4.9.3 Membrane structure 287
4.9.4 Targets of attack: fatty acids and lipoproteins 289
4.9.5 How does lipid peroxidation begin? 291
4.9.6 Propagation of lipid peroxidation 293
4.9.7 Iron and lipid peroxidation 296
4.9.8 Which iron chelates stimulate lipid peroxidation? 298
4.9.9 Copper and other metals as promoters of lipid
peroxidation 299
4.9.10 Products of peroxide decomposition 300
4.9.11 Damage to membrane proteins during lipid
peroxidation 304
4.9.12 Toxicity of peroxides 306
4.9.13 Isoprostanes 307
4.9.14 Platelet activating factor and lipid peroxidation 307
4.9.15 Cholesterol oxidation 308
4.9.16 Peroxidation of microsomes 310
4.9.17 Acceleration of lipid peroxidation by species other
than oxygen radicals 311
4.9.18 Peroxidation of other molecules 313
4.9.19 Repair of lipid peroxidation 313
4.10 Mechanisms of damage to cellular targets by oxidative
stress: protein damage 313
4.10.1 Chemistry and significance of protein damage 315
4.10.2 Damage to specific amino acid residues 316
4.11 Consequences of oxidative protein damage: interference
with cell function 319
4.12 How organisms deal with oxidative protein damage 320
4.12.1 Repair 320
4.12.2 Protein degradation 321
4.12.3 The proteasome 321
4.13 Consequences of oxidative stress: adaptation 322
4.13.1 Bacterial redox regulation: o.vyR 322
4.13.2 Bacterial redox regulation: .so.vRS 323
4.13.3 Bacterial redox regulation: the role of iron 323
4.13.4 Redox regulation in yeast 324
4.13.5 Redox regulation in mammals: NF kB 324
4.13.6 Redox regulation in mammals: AP 1 and the
antioxidant response element 326
4.13.7 GA binding protein 327
Contents xvii
4.14 Are ROS/RNS important signal molecules in Vivo? 327
4.14.1 It can occur, but does it matter? 329
4.15 Heat shock and related stress induced proteins 330
4.15.1 Chaperones 331
4.15.2 The role of ubiquitin 333
4.15.3 Haem oxygenase as a heat shock protein 333
4.15.4 Bacterial stress proteins 333
4.15.5 Heat shock transcription factor 334
4.16 Cytokines 334
4.16.1 TNFa 335
4.16.2 Interleukins 336
4.16.3 The acute phase response 336
4.17 Consequences of oxidative stress: cell death 337
4.17.1 Necrosis 337
4.17.2 Apoptosis 338
4.17.3 Genetics and mechanism of apoptosis 340
4.18 Summary: what is oxidative stress? 341
References 343
Notes 350
5 Detection of free radicals and other reactive species:
trapping and fingerprinting 351
5.1 Introduction 351
5.2 ESR and spin trapping 352
5.2.1 Spin trapping 355
5.2.2 DMPO and PBN 357
5.2.3 Metabolism of spin traps 359
5.2.4 Trapping of thiyl radicals 360
5.3 Other trapping methods, as exemplified by
hydroxyl radical trapping 361
5.3.1 Aromatic hydroxylation 361
5.3.2 The deoxyribose assay for hydroxyl radical 366
5.3.3 Other trapping methods for hydroxyl radical 370
5.4 Detection of superoxide 370
5.4.1 Histochemical detection 371
5.5 Detection of nitric oxide 376
5.5.1 Interference by peroxynitrite 376
5.5.2 Calibration 377
5.6 Detection of peroxynitrite 377
5.6.1 Nitration assays 377
5.7 Detection of chlorinating species 379
5.8 Detection of hydrogen peroxide 380
5.8.1 Dichlorofluorescin diacetate 381
5.9 Detection of singlet oxygen 385
5.9.1 Direct detection 385
5.9.2 Use of scavengers and traps 386
xviii Contents
5.9.3 Deuterium oxide 386
5.10 Studies of generalized light emission
(luminescence/fluorescence) 387
5.10.1 Luminol and lucigenin 387
5.11 Fingerprinting methods:
oxidative DNA damage 388
5.11.1 Introduction 388
5.11.2 Products of DNA damage 388
5.11.3 DNA damage in vivo 389
5.11.4 Measurement of oxidative DNA damage:
basic principles 390
5.11.5 Measurement of guanine damage products in
isolated DNA 390
5.11.6 DNA isolation problems 392
5.11.7 DNA aldehyde adducts 393
5.12 Fingerprinting methods: lipid peroxidation 393
5.12.1 Measurement of lipid peroxidation; general
principles 393
5.12.2 Loss of substrates 393
5.12.3 Measurement of peroxides 399
5.12.4 Diene conjugation 400
5.12.5 Interpretation of conjugated diene assays 400
5.12.6 Measurement of hydrocarbon gases 402
5.12.7 Light emission 404
5.12.8 Measurement of fluorescence 405
5.12.9 Parinaric acid 407
5.12.10 The thiobarbituric acid test 407
5.12.11 Urinary TBARS 411
5.12.12 Isoprostanes 411
5.12.13 Aldehydes other than MDA:
4 hydroxy 2 tra«s nonenal 412
5.12.14 Summary 412
5.13 Fingerprinting methods: protein damage by
ROS and RNS 413
5.13.1 Reactive nitrogen species 413
5.13.2 Reactive chlorine species 416
5.13.3 Reactive oxygen species 416
5.13.4 The carbonyl assay 416
5.13.5 Can total oxidative protein damage be
measured in vivo? 417
5.14 Fingerprinting methods: small molecules 422
5.14.1 Ascorbate 422
5.14.2 Uric acid 422
5.15 Assays of total antioxidant activity 422
5.15.1 How useful are total antioxidant assays? 425
References 425
Contents xix
6 Reactive species as useful biomolecules 430
6.1 Introduction 430
6.2 Radical enzymes: ribonucleotide reductase 430
6.2.1 The enzyme mechanism 431
6.2.2 Inhibitors of the enzyme 432
6.2.3 An alternative radical 432
6.3 Cobalamin radical enzymes 432
6.4 Pyruvate metabolizing enzymes 434
6.5 Oxidation, carboxylation and hydroxylation
reactions 435
6.6 Yet more useful peroxidase enzymes 436
6.6.1 Thyroid hormone synthesis 437
6.6.2 An anti molestation spray 437
6.6.3 A fertilization membrane 438
6.6.4 Lignification and ligninolysis 439
6.6.5 Light production 441
6.7 Phagocytosis 442
6.7.1 Phagocyte recruitment and adhesion 446
6.7.2 The killing mechanism of phagocytes 448
6.7.3 Significance of extracellular ROS/RNS production
by phagocytes 462
6.7.4 Bacterial and fungal avoidance strategies 465
6.8 NAD(P)H oxidases in other cell types 465
6.8.1 Endothelial cells 465
6.8.2 Lymphocytes and fibroblasts 466
6.8.3 Sensing of hypoxia 466
6.8.4 Platelets 466
6.8.5 Other cells 467
6.9 Fruit ripening and the wound response of plant tissues 467
6.9.1 Lipoxygenases 467
6.9.2 The wound response 469
6.9.3 The hypersensitive response 470
6.10 Animal lipoxygenases and cyclooxygenases: stereospecific
lipid peroxidation 471
6.10.1 Eicosanoids: prostaglandins and leukotrienes 471
6.10.2 Prostaglandins and thromboxanes 471
6.10.3 Prostaglandin structure 473
6.10.4 Prostaglandin synthesis 473
6.10.5 Regulation by peroxide tone 474
6.10.6 Prostacyclins and thromboxanes 476
6.10.7 Gene knockouts 477
6.10.8 Leukotrienes and other lipoxygenase
products 478
6.10.9 Commercial PUFAs: a warning 481
References 481
Notes 484
xx Contents
7 Oxidative stress and antioxidant protection: some
special cases 485
7.1 Introduction 485
7.2 Erythrocytes 485
7.2.1 What problems do erythrocytes face? 487
7.2.2 Solutions: antioxidant defence enzymes 489
7.2.3 Solutions: low molecular mass antioxidants 490
7.2.4 Erythrocyte peroxidation in health and disease 490
7.2.5 Glucose 6 phosphate dehydrogenase deficiency 491
7.2.6 Solutions: destruction 491
7.3 Erythrocytes as targets for toxins 493
7.3.1 Nitrite 493
7.3.2 Hydrazines 493
7.3.3 Sulphur containing haemolytic drugs 495
7.4 Inborn defects in erythrocyte antioxidant defences:
the link to malaria 495
7.4.1 Favism 495
7.4.2 Malaria, oxidative stress and an ancient Chinese herb 497
7.5 Chloroplasts 499
7.5.1 Structure and genetics 499
7.5.2 Trapping of light energy 499
7.5.3 The splitting of water 501
7.5.4 What problems do chloroplasts face? 502
7.5.5 Catalytic metal ions in plants? 505
7.5.6 Solutions: antioxidant defence enzymes 505
7.5.7 Ascorbate and glutathione 507
7.5.8 Plant tocopherols 507
7.5.9 Carotenoids 508
7.5.10 The xanthophyll cycle 509
7.5.11 Solutions: repair and replacement 510
7.6 Chloroplasts as targets for toxins 510
7.6.1 Inhibition of electron transport and carotenoid synthesis 510
7.6.2 Bipyridyl herbicides 511
7.6.3 Air pollutants 514
7.6.4 Environmental stress 515
7.7 The eye 516
7.7.1 What problems does the eye face? 518
7.7.2 Solutions 519
7.7.3 The question of carotenoids 521
7.8 Reproduction and oxidative stress 522
7.8.1 Pre conception 522
7.8.2 Post conception 524
7.8.3 Normal and premature birth 526
7.9 The skin 529
7.9.1 Insults to the skin 530
7.9.2 Inflammation 533
Contents xxi
7.9.3 The solutions 534
7.10 Exercise: an oxidative stress? 534
7.10.1 Does exercise cause oxidative damage? 535
7.10.2 Exercise, health and free radicals 536
7.10.3 Muscle as a target for toxins 536
References 537
Notes 543
8 Free radicals, reactive species and toxicology 544
8.1 Introduction 544
8.1.1 What is toxicology? 544
8.1.2 Principles of toxin metabolism 544
8.1.3 How can ROS/RNS contribute to toxicology? 546
8.2 Carbon tetrachloride 547
8.2.1 CCU synthesis: a free radical chain reaction 548
8.2.2 Toxicity of CC14 548
8.2.3 How does CC1* cause damage? 550
8.3 Other halogenated hydrocarbons 552
8.3.1 Chloroform and bromotrichloromethane 553
8.3.2 Bromoethane and bromobenzene 553
8.3.3 Halothane 554
8.3.4 Molecules similar to halothane 556
8.3.5 Pentachlorophenol and related environmental
pollutants 556
8.4 Redox cycling toxins: bipyridyl herbicides 557
8.4.1 Toxicity to bacteria 557
8.4.2 Protection by extracellular SOD 557
8.4.3 Toxicity to animals 558
8.4.4 Why is paraquat toxic to the lung? 559
8.4.5 Paraquat, lipid peroxidation and hydroxyl radical
formation 560
8.5 Diabetogenic drugs 561
8.5.1 Alloxan 561
8.5.2 Streptozotocin 563
8.6 Redox cycling toxins: diphenols and quinones 564
8.6.1 Interaction with O; and superoxide 564
8.6.2 Formation of hydroxyl radical 565
8.6.3 Menadione and quinone reductase
(DT diaphorase) 566
8.6.4 Substituted dihydroxyphenylalanines and
manganese madness 569
8.6.5 Neurotoxicity of 6 hydroxydopamine 570
8.6.6 Methyl DOPA 570
8.6.7 Benzene and its derivatives 570
8.6.8 Toxic oil syndrome 571
xxii Contents
8.7 Redox cycling agents: toxins derived from Pseudomonas
aeruginosa 572
8.8 Alcohols 573
8.8.1 Ethanol 573
8.8.2 Allyl alcohol and acrolein 575
8.9 Paracetamol (acetaminophen) 576
8.10 Air pollutants 577
8.10.1 Nitrogen dioxide 577
8.10.2 Ozone 581
8.10.3 Sulphur dioxide 583
8.10.4 Mixtures 584
8.11 Toxicity of complex mixtures: cigarette smoke and other
toxic smokes 584
8.11.1 Chemistry of cigarette smoke 584
8.11.2 Mechanisms of damage by cigarette smoke 587
8.11.3 Lung defences against cigarette smoke 588
8.11.4 Adaptation 589
8.11.5 Other tobacco usage 590
8.11.6 Fire smoke 590
8.11.7 Diesel exhaust 590
8.12 Toxicity of metals 591
8.12.1 Cause or consequence? 591
8.12.2 Titanium 591
8.12.3 Aluminium 591
8.12.4 Lead 594
8.12.5 Vanadium 594
8.12.6 Molybdenum 595
8.12.7 Chromium 595
8.12.8 Nickel 596
8.12.9 Cobalt 596
8.12.10 Mercury 597
8.12.11 Cadmium 597
8.12.12 Arsenic 597
8.13 Antibiotics 598
8.13.1 Peroxidation of antibiotics 598
8.13.2 Tetracyclines as pro and anti oxidants 598
8.13.3 Quinone antibiotics 600
8.13.4 Aminoglycoside nephrotoxicity and ototoxicity 600
8.14 Nitro and azo compounds 601
8.14.1 Nitro radicals and redox cycling 601
8.14.2 Further reduction of nitro radicals 601
8.14.3 Cocaine teratogenicity 603
8.14.4 Azo compounds 603
8.15 3 Methylindole 604
8.16 Radiation damage 604
8.16.1 The oxygen effect 605
Contents xxiii
8.16.2 The role of superoxide 606
8.16.3 Hypoxic cell sensitizers 607
8.16.4 Food irradiation 608
8.17 General conclusion 608
References 609
9 Free radicals, other reactive species and disease 617
9.1 Introduction 617
9.1.1 Origin of oxidative stress in disease 619
9.1.2 Consequences of oxidative stress in disease 621
9.1.3 Significance of oxidative stress in disease 623
9.2 Atherosclerosis 625
9.2.1 Nature of atherosclerosis 625
9.2.2 The link to fat 625
9.2.3 What initiates atherosclerosis? 626
9.2.4 What roles are played by ROS/RNS in
atherosclerosis? 627
9.2.5 Evidence relating to the oxidation theory
of atherosclerosis 630
9.2.6 Chemistry of LDL oxidation 631
9.2.7 Antioxidants and LDL oxidation 634
9.2.8 The role of high density lipoproteins 637
9.2.9 Conclusion 638
9.3 Hypertension 638
9.4 Diabetes 639
9.4.1 Oxidative stress and the origins of diabetes 639
9.4.2 Oxidative stress in diabetic patients 640
9.4.3 Mechanisms of glucose toxicity: aldose reductase 641
9.4.4 Non enzymatic glycation and glycoxidation 641
9.4.5 How important is oxidative stress in diabetes? 645
9.5 Ischaemia—reperfusion 645
9.5.1 Consequences of hypoxia 646
9.5.2 Reoxygenation injury 646
9.5.3 Adaptation to hypoxia: the role of transcription
factors 648
9.5.4 Intestinal ischaemia reoxygenation 648
9.5.5 Cardiac ischaemia reoxygenation 649
9.5.6 Ischaemic preconditioning 654
9.5.7 Shock related ischaemia—reoxygenation 655
9.5.8 Birth trauma 655
9.5.9 Kidney damage 656
9.5.10 Liver transplantation 658
9.5.11 Organ preservation fluids 658
9.5.12 The eye 659
9.5.13 Limbs, digits, and sex organs 659
9.5.14 Plants 660
xxiv Contents
9.5.15 Chemical ischaemia—reoxygenation: carbon
monoxide poisoning 660
9.5.16 Freezing injury 660
9.6 Chronic inflammatory diseases: an introduction 661
9.6.1 Anti inflammatory effects of antioxidants 661
9.6.2 Tissue damage by inflammation 662
9.6.3 Are ROS/RNS important mediators of
autoimmune diseases? 663
9.6.4 Clastogenic factors 663
9.6.5 Antiphospholipid antibodies 664
9.6.6 Artefacts of sample storage: a cautionary note 664
9.7 Rheumatoid arthritis 664
9.7.1 The normal joint 665
9.7.2 The RA joint 665
9.7.3 Oxidative damage in RA 666
9.7.4 Sources of ROS/RNS in RA 667
9.7.5 Consequences of oxidative damage in RA 674
9.7.6 Iron and rheumatoid arthritis 675
9.7.7 Alkaptonuria 677
9.8 Inflammatory bowel disease 677
9.8.1 The salazines 678
9.9 Other chronic inflammations 678
9.9.1 The pancreas 678
9.9.2 Other parts of the gastro intestinal tract 679
9.10 Lung damage and the adult respiratory distress syndrome 679
9.10.1 Oxygen and the lung 679
9.10.2 Phagocytes and adult respiratory distress syndrome 680
9.10.3 Oxidative stress and ARDS 681
9.10.4 Lung transplantation 684
9.10.5 Asthma 684
9.11 Cystic fibrosis 685
9.11.1 Cystic fibrosis and carotenoids 686
9.12 Oxidative stress and cancer: a complex relationship 687
9.12.1 The cell cycle 687
9.12.2 Tumours 688
9.12.3 Carcinogenesis 689
9.12.4 Oncogenes 691
9.12.5 Tumour suppressor genes 694
9.12.6 ROS/RNS and carcinogenesis 694
9.12.7 Changes in antioxidant defences in cancer 699
9.12.8 Transition metals and cancer 700
9.13 Carcinogens: oxygen and others 701
9.13.1 Carcinogen metabolism 702
9.13.2 Benzpyrene 705
9.13.3 Detoxification of carcinogens 705
9.13.4 Carcinogens and oxidative DNA damage 706
Contents xxv
9.13.5 Peroxisome proliferators 706
9.13.6 Reactive nitrogen species 707
9.14 Cancer chemotherapy 710
9.14.1 Natural products in chemotherapy 710
9.14.2 Bleomycin 711
9.14.3 Quinone antitumour agents 715
9.14.4 Protein antitumour drugs 720
9.14.5 Resistance to cancer chemotherapy 721
9.15 Oxidative stress and disorders of the nervous
system: general principles 721
9.15.1 Introduction 721
9.15.2 Energy metabolism 722
9.15.3 Calcium and nitric oxide 723
9.15.4 Excitotoxicity 725
9.15.5 Why should the brain be prone to oxidative stress? 726
9.15.6 Consequences of oxidative stress 729
9.15.7 Antioxidant defences in the brain 731
9.16 Oxidative stress and ischaemic or traumatic brain injury 733
9.16.1 Definition of terms 733
9.16.2 Mediators of damage 734
9.16.3 Therapeutic interventions 735
9.16.4 Traumatic injury 735
9.17 Oxidative stress in Parkinson s disease 736
9.17.1 Pathology of the disease 736
9.17.2 Treatment 737
9.17.3 What is the cause of PD? 738
9.17.4 Oxidative stress and mitochondrial defects in PI) 740
9.17.5 Distinguishing cause from consequence 740
9.18 Oxidative stress in Alzheimer s disease 744
9.18.1 Pathology of the disease 744
9.18.2 The nature of amyloid m AD 746
9.18.3 Genetics of AD 748
9.18.4 Mechanisms of plaque toxicity 749
9.18.5 Aluminium in Alzheimer s disease 750
9.19 Amyotrophic lateral sclerosis 751
9.19.1 ALS and superoxide dismutase 751
9.19.2 Mechanisms of SOD toxicity 752
9.19.3 Oxidative damage in ALS 754
9.20 Other neurodegenerative diseases 755
9.20.1 Down s syndrome 755
9.20.2 Multiple sclerosis 755
9.20.3 Neuronal ceroid lipofuscinoses 756
9.20.4 Huntington s disease 757
9.20.5 Friedreich s ataxia 758
9.20.6 Tardive dyskinesia 759
9.20.7 Prion diseases 759
xxvi Contents
9.20.8 Does emotional stress lead to oxidative stress? 760
9.21 Oxidative stress and viral infections 761
9.21.1 Origin of oxidative stress 761
9.21.2 HIV infection 762
9.21.3 Oxidative stress in HIV disease? 764
9.21.4 Redox regulation of viral expression 765
9.21.5 Drug toxicity 765
9.22 Conclusion 767
References 767
Notes 783
10 Ageing, nutrition, disease and therapy: a role
for antioxidants? 784
10.1 Introduction 784
10.2 Theories of ageing 784
10.2.1 General principles of ageing 784
10.2.2 What features of ageing must theories explain? 785
10.2.3 Genetic theories of ageing 786
10.2.4 Human disorders of premature ageing 786
10.2.5 Telomeres and telomerase 788
10.2.6 Damage accumulation theories of ageing 789
10.3 Oxidative damage: a common link between all the
ageing theories? 790
10.3.1 Experimental tests of the theory: altering
antioxidant levels 793
10.3.2 Transgenic organisms 795
10.3.3 Does antioxidant protection fail with age? 796
10.3.4 Does net oxidative damage increase with age? 798
10.3.5 Lipofuscin 799
10.3.6 Ceroid 800
10.3.7 The free radical theory of ageing: current status 802
10.3.8 Differentiation 802
10 4 Nutrition, health and oxidative stress 803
10.4.1 Lessons from epidemiology 803
10.4.2 Problems of interpretation 805
10.4.3 Types of study 806
10.4.4 Cause and consequence 807
10.4.5 Experimental epidemiology 811
10.4.6 The need for biomarkers 813
10.4.7 Some examples of epidemiological studies 814
10.4.8 A status summary: antioxidants and
cardiovascular disease 816
10.4.9 The Linxian study 817
10.4.10 The Finnish study (a tocopherol//? carotene
cancer prevention study) and CARET 817
10.4.11 Other dietary factors and cardiovascular disease 819
Contents xxvii
10.5 Antioxidants and the treatment of disease 820
10.5.1 Therapeutic antioxidants 820
10.5.2 Approaches to antioxidant characterization 821
10.5.3 Superoxide dismutase 828
10.5.4 Mimics of SOD 831
10.5.5 Spin traps 832
10.5.6 Vitamins C and E and their derivatives 837
10.5.7 Other chain breaking antioxidants: probucol
and ubiquinol 838
10.5.8 BHA, BHT and plant phenolics 839
10.5.9 The lazaroids 839
10.5.10 Thiol compounds 840
10.5.11 Glutathione peroxidase mimics 842
10.6 Iron chelators 843
10.6.1 Desferrioxamine 843
10.6.2 Other iron chelating agents 851
10.7 Inhibitors of ROS/RNS generation 852
10.7.1 Xanthine oxidase inhibitors 852
10.7.2 Inhibitors of ROS generation by phagocytes 853
10.7.3 Inhibitors of nitric oxide synthase 854
References 854
Notes 859
Appendix I Some basic chemistry for the life scientist 860
A 1.1 Atomic structure 860
A1.2 Bonding between atoms 868
Al .2.1 Ionic bonding 868
Al.2.2 Covalent bonding 869
A 1.2.3 Non ideal character of bonds 871
A 1.2.4 Hydrocarbons and electron
delocalization 873
A1.3 Moles and molarity 875
A 1.4 pH and pK, 875
A 1.5 Some useful data 87(
Appendix II Some basic molecular biology for the chemist 880
A2.1 Introduction 880
A2.2 Transcription and editing 881
A2.3 Translation 881
A2.4 Regulation ot transcription 883
A2.5 Structure and regulation ot
transcription factors 885
A2.5.1 Zinc fingers 885
A2.5.2 Leucine zippers 88(
A2.6 Cell growth signals, kinases and immediate
early genes K8f
xxviii Contents
A2.7 Identifying DNA binding proteins in the
laboratory 887
A2.8 Reverse transcription 888
A2.9 Studying the genome 888
A2.10 Recombinant DNA technology 890
A2.11 Libraries 891
A2.12 Polymerase chain reaction 892
A2.13 Gene expression in mammalian cells 892
A2.14 Antisense technology 894
A2.15 Transgenic organisms 894
References 897
Index 899
|
| any_adam_object | 1 |
| author | Halliwell, Barry Gutteridge, John M. |
| author_facet | Halliwell, Barry Gutteridge, John M. |
| author_role | aut aut |
| author_sort | Halliwell, Barry |
| author_variant | b h bh j m g jm jmg |
| building | Verbundindex |
| bvnumber | BV012149567 |
| callnumber-first | R - Medicine |
| callnumber-label | RB170 |
| callnumber-raw | RB170 |
| callnumber-search | RB170 |
| callnumber-sort | RB 3170 |
| callnumber-subject | RB - Pathology |
| classification_rvk | WD 2200 WD 4750 |
| ctrlnum | (OCoLC)300190044 (DE-599)BVBBV012149567 |
| dewey-full | 616.07 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.07 |
| dewey-search | 616.07 |
| dewey-sort | 3616.07 |
| dewey-tens | 610 - Medicine and health |
| discipline | Biologie Medizin |
| edition | 3. ed. |
| format | Book |
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| id | DE-604.BV012149567 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:22:33Z |
| institution | BVB |
| isbn | 0198500459 0198500440 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-008228784 |
| oclc_num | 300190044 |
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| owner | DE-20 DE-634 DE-11 |
| owner_facet | DE-20 DE-634 DE-11 |
| physical | XXXI, 936 S. Ill., graph. Darst. |
| publishDate | 1999 |
| publishDateSearch | 1999 |
| publishDateSort | 1999 |
| publisher | Oxford Univ. Press |
| record_format | marc |
| series2 | Oxford science publications |
| spelling | Halliwell, Barry Verfasser aut Free radicals in biology and medicine Barry Halliwell and John M. C. Gutteridge 3. ed. Oxford [u.a.] Oxford Univ. Press 1999 XXXI, 936 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Oxford science publications Antioxydants - Physiologie Biochimie ram Biologie - Recherche Biologie ram Médecine - Recherche Pathologie moléculaire ram Radical libre (Biologie) Radicaux libres (Chimie) - Effets physiologiques Radicaux libres (chimie) ram Radicaux libres - Physiologie Réactions chimiques Réactions radicalaires Stress oxydatif Superoxyde - Effets physiologiques Hyperoxide (DE-588)4161081-7 gnd rswk-swf Freies Radikal (DE-588)4137149-5 gnd rswk-swf Biologie (DE-588)4006851-1 gnd rswk-swf Biologisches System (DE-588)4122930-7 gnd rswk-swf Biochemie (DE-588)4006777-4 gnd rswk-swf Physiologische Chemie (DE-588)4076124-1 gnd rswk-swf Medizin (DE-588)4038243-6 gnd rswk-swf Antioxidans (DE-588)4142729-4 gnd rswk-swf Biochemie (DE-588)4006777-4 s Freies Radikal (DE-588)4137149-5 s Antioxidans (DE-588)4142729-4 s Hyperoxide (DE-588)4161081-7 s Biologisches System (DE-588)4122930-7 s 1\p DE-604 Medizin (DE-588)4038243-6 s 2\p DE-604 Biologie (DE-588)4006851-1 s 3\p DE-604 Physiologische Chemie (DE-588)4076124-1 s 4\p DE-604 Gutteridge, John M. Verfasser aut HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=008228784&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 3\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 4\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Halliwell, Barry Gutteridge, John M. Free radicals in biology and medicine Antioxydants - Physiologie Biochimie ram Biologie - Recherche Biologie ram Médecine - Recherche Pathologie moléculaire ram Radical libre (Biologie) Radicaux libres (Chimie) - Effets physiologiques Radicaux libres (chimie) ram Radicaux libres - Physiologie Réactions chimiques Réactions radicalaires Stress oxydatif Superoxyde - Effets physiologiques Hyperoxide (DE-588)4161081-7 gnd Freies Radikal (DE-588)4137149-5 gnd Biologie (DE-588)4006851-1 gnd Biologisches System (DE-588)4122930-7 gnd Biochemie (DE-588)4006777-4 gnd Physiologische Chemie (DE-588)4076124-1 gnd Medizin (DE-588)4038243-6 gnd Antioxidans (DE-588)4142729-4 gnd |
| subject_GND | (DE-588)4161081-7 (DE-588)4137149-5 (DE-588)4006851-1 (DE-588)4122930-7 (DE-588)4006777-4 (DE-588)4076124-1 (DE-588)4038243-6 (DE-588)4142729-4 |
| title | Free radicals in biology and medicine |
| title_auth | Free radicals in biology and medicine |
| title_exact_search | Free radicals in biology and medicine |
| title_full | Free radicals in biology and medicine Barry Halliwell and John M. C. Gutteridge |
| title_fullStr | Free radicals in biology and medicine Barry Halliwell and John M. C. Gutteridge |
| title_full_unstemmed | Free radicals in biology and medicine Barry Halliwell and John M. C. Gutteridge |
| title_short | Free radicals in biology and medicine |
| title_sort | free radicals in biology and medicine |
| topic | Antioxydants - Physiologie Biochimie ram Biologie - Recherche Biologie ram Médecine - Recherche Pathologie moléculaire ram Radical libre (Biologie) Radicaux libres (Chimie) - Effets physiologiques Radicaux libres (chimie) ram Radicaux libres - Physiologie Réactions chimiques Réactions radicalaires Stress oxydatif Superoxyde - Effets physiologiques Hyperoxide (DE-588)4161081-7 gnd Freies Radikal (DE-588)4137149-5 gnd Biologie (DE-588)4006851-1 gnd Biologisches System (DE-588)4122930-7 gnd Biochemie (DE-588)4006777-4 gnd Physiologische Chemie (DE-588)4076124-1 gnd Medizin (DE-588)4038243-6 gnd Antioxidans (DE-588)4142729-4 gnd |
| topic_facet | Antioxydants - Physiologie Biochimie Biologie - Recherche Biologie Médecine - Recherche Pathologie moléculaire Radical libre (Biologie) Radicaux libres (Chimie) - Effets physiologiques Radicaux libres (chimie) Radicaux libres - Physiologie Réactions chimiques Réactions radicalaires Stress oxydatif Superoxyde - Effets physiologiques Hyperoxide Freies Radikal Biologisches System Biochemie Physiologische Chemie Medizin Antioxidans |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=008228784&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT halliwellbarry freeradicalsinbiologyandmedicine AT gutteridgejohnm freeradicalsinbiologyandmedicine |