Free Radical Damage and its Control (eBook)

Front Cover 1
Free Radical Damage and its Control 4
Copyright Page 5
Contents 10
Preface 6
List of contributors 8
Part I: Chemical and Biochemical Aspects 18
Chapter 1. Chemistry of iron and copper in radical reactions 20
Abbreviations 20
1. Introduction 20
2. Autoxidation reactions 23
3. Fenton reactions 28
4. Speciation and effectiveness in promoting oxyradical damage 35
Acknowledgement 37
References 37
Chapter 2. Some chemical and biochemical constraints of oxidative stress in living cells 42
Abbreviations 42
1. The birth of the concept 42
2. The basic properties of oxygen and the concept of oxygen activation 44
3. The puzzling toxicity of superoxide 51
4. Toxicity of hydroperoxides and their radical by-products 56
5. Iron transport and the iron-transit pool 62
6. Protective pathways of mammalian cells and tissues 63
7. Protein S-thiolation: signal or damage? 71
8. Conclusion 74
References 75
Chapter 3. Ferryl iron and protein free radicals 84
Abbreviations 84
1. Introduction 84
2. Chemical structure of FeIV 87
3. Enzyme catalysis by ferryl ion and free radicals 89
4. Methods for detecting ferryl iron and protein free radicals 100
5. Radicals and disease – ferryl gone wrong 117
Acknowledgements 120
References 121
Chapter 4. Antioxidants and free radical scavengers 130
1. Introduction 130
2. Enzymatic mechanisms of protection 131
3. Control of secondary radicals 136
4. Removal of lipid hydroperoxides 143
5. Other antioxidant mechanisms 144
References 145
Chapter 5. Formation of free radicals and mechanisms of action in normal biochemical processes and pathological states 148
1. Free radical-generating systems in normal processes in vivo 148
2. Free radical-mediated tissue damage 150
3. Haem proteins and the potential for the formation of reactive radical species in pathological states 158
Acknowledgements 168
References 168
Chapter 6. Free radicals and cell proiferation 172
1. Introduction 172
2. Proliferation of mammalian cells 172
3. Oxidative stress and cell proliferation 175
4.Oxygen radicals, and related species that stimulate cell proliferation 180
5. Cellular rclease of superoxide and hydrogen peroxide 181
6. lntracellular generation of superoxide 182
7. Superoxide and hydrogen peroxide as cellular 'massengers' 183
8. Mechanisms whereby superoxide and hydrogen peroxide promote cell growth or growth responses 185
9. Active oxygen species and normal cell proliferation 191
10. Active oxygen species and carcinogenesis 192
11. Radicals and the role of ribonucleotide reductase 196
12. An overview 196
References 197
Part II: Pathological Aspects 204
Chapter 7. Therapeutic iron-chelating agents 206
1.Introduction 206
2. Iron overload 208
3. Bidentate and hexadentate iron chelators 210
4. Chelation therapy 211
5. Requirements for selective iron chelation 212
6. Design of orally active chelating agents 216
7. Localised and temporary elevation of iron levels 218
8. Selective inhibition of non-hacm-containing enzymes 224
9. Treatment of anaemia with iron complexes 229
10. Conclusion 230
References 230
Chapter 8. Free radicals in central nervous system injury 234
1. Introduction 234
2. Oxygen radicals in spinal cord injury 235
3. Oxygen radicals in head injury 245
4. Clinical evidence of the importance of oxygen radicals in CNS injury 249
5. Summary 250
References 251
Chapter 9. Ultraviolet radiation (UVA, UVB) and skin antioxidants 256
1. Introduction 256
2. Studies on excised hairless mouse skin 257
3. In vivo irradiation of hairless mouse skin 262
4. Conclusions 268
Acknowledgements 270
References 270
Chapter 10. Free radicals and atherosclerosis 274
1. Introduction 274
2. Arterial wall and oxyradicals 274
3. Oxidised low-density lipoproteins (Ox-LDL) 276
4. The macrophage scavenger receptors (Fig. 1 ) 287
5. Ox-LDL and vasoconstriction 290
6. Arrhythmogenic effects of Ox-LDL 292
7. Conclusion 292
References 293
Chapter 11. Chemical aspects of free radical reactions in connective tissue 298
1. Introduction 298
2. Reactions of free radicals with hyaluronic acid in simple solutions 302
References 315
Chapter 12. Free radicals and connective tissue damage 318
1. Introduction 318
2. The release of reactive oxygen intermediates (ROls) during inflammation 318
3. Composition and organization of connective tissues (with special reference to articular cartilage) 319
4. Connective tissue injury by oxidants 322
References 333
Chapter 13. Free radicals in toxicology with an emphasis on electron spin resonance investigations 336
1. Introduction 336
2. Detection and identification of free radicals in biological systems 337
3. Criteria for free radical toxicity 338
4. Formation of free radicals in biological sysems 339
5. Spin trapping 344
6. Conclusions 347
References 347
Chapter 14. Radical generation and detection in myocardial injury 350
1. Free radicals in myocardial injury 350
2. Indirect evidence for the role of the oxy radicals 351
3. Compartmentalization of radical reactions in the heart 352
4. Detection of oxygen-derived free radicals 355
5. Spin traps in myocardial ischemia and reperfusion injury 359
6. Future prospects 371
Acknowledgments 372
References 372
Chapter 15. Free radical pathways in the inflammatory response 378
1. Introduction 378
2. The generation of free radicals in inflammatory diseases 378
3. Inhibition of free radical pathways in inflammation 382
4. Pathways involving free radicals as second messengers in inflammation – some topical examples 384
5. Free radical pathways of macromolecular damage and tissue destruction – some topical examples 389
Acknowledgements 396
References 396
Index 402