86. Natural Antioxidants In Human Health & Disease

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86. Natural Antioxidants In Human Health & Disease

 

 

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COURSE NUMBER: 86

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Syllabus

Contributors xv
Foreword xix
BRUCE N. AMES
Preface xxvii
BALZ FREI

I. Oxidants and Antioxidants
1. Free Radicals and Lipid Peroxidation: What They Are
and How They Got That Way
WILLIAM A. PRYOR
I. Introduction
II. Putting the Proper Spin on Radicals 2
III. Radical Lifetimes 4
IV. Radical Chain Reactions and Lipid Autoxidation 6
V. Autoxidation and Kinetic Chain Length 10
VI. The Effects of Antioxidants I I
VII. Sources of Radicals in Living Systems 13

VIII. Cooxidations and Related Troublemakers 15
IX. Generation of Radicals in the Lipid or Water Phase 16
X. Autoxidation of PUFAs in LDL 17
XI. Epilogue 19
References 19
2. Free Radicals in Biology: Sources, Reactivities, and Roles
in the Etiology of Human Diseases
JAMES P. KEHRER and CHARLES V. SMITH
I. Introduction 25
II. Definitions 27
III. Chemistry and Reactivity of Free Radicals in Biological Systems 30
IV. Cellular Sources of Free Radicals 33
V. Radical Reactivity in Biological Systems 38
VI. Free Radicals, Antioxidants, and Disease 40
VII. Conclusions 54
References 55
3. Oxidants and Mitochondrial Decay in Aging
MARK K. SHIGENAGA and BRUCE N. AMES
I. Introduction 63
II. Age-Related Oxidative Damage to Cellular Macromolecules 65
III. Age-Related Changes in Mitochondria 72
IV. Effects of Calorie Restriction on Mitochondrial Function
and Reactive Oxygen Species Production 84
V. Role of Mitochondrial Dysfunction and Reactive Oxygen
Species in the Neuroendocrine, Immune,
and Glycation Theories of Aging 88
VI. Summary 95
References 96

4. Nonenzymatic Antioxidant Defense Systems
KARLIS BRIVIBA and HELMUT SIES
I. Introduction 107
II. Water-Soluble Antioxidants 110
III. Lipid-Soluble Antioxidants 113
IV. Concluding Remarks 121
References 122

II. Cancer

5. Ascorbic Acid and Cancer: Animal and Cell Culture Data
GLADYS BLOCK and RICHARD SCHWARZ
I. Introduction 129
II. Animal Data 129
III. Cell Culture Studies of Possible Mechanisms
of Ascorbate Action 142
IV. Conclusions 149
References 149
6. Vitamin C, Vitamin C-Rich Foods, and Cancer:
Epidemiologic Studies
ELIZABETH T. H. FONTHAM
I. Introduction 157
II. Analytic Studies by Cancer Site 159
III. Chemoprevention Trials 184
IV. Summary 188
References 189
7. Vitamin E and Cancer Prevention
PAUL KNEKT
I. Introduction 199
II. Vitamin E 199
III. Experimental Models 202
IV. Epidemiologic Studies 206
V. Intervention Trials 227
VI. Conclusions and Recommendations 227
References 228
8. Carotenoids and Cancer: Basic Research Studies
NORMAN I. KRINSKY
I. Introduction 239
II. How Do Carotenoids Interact with Cells? 240
III. How Do Carotenoids Prevent Cancer in Animals? 246
IV. Can Dietary ~-Carotene Materially Reduce
Human Cancer Rates? 252
V. Mechanisms of Carotenoid Anticarcinogenesis 254
VI. Summary 255
References 255

9. The Epidemiology of Selenium and Human Cancer
MIRIAM GARLAND, MEIRJ. STAMPFER, WALTER C. WILLEn,
and DAVID J. HUNTER
I. Introduction 263
II. Ecologic Studies 264
III. Analytical Epidemiologic Studies 265
IV. Conclusions and Outlook 280
References 281
III. Cardiovascular Disease

10. The Pathogenesis of Atherosclerosis
COLIN J. SCHWARTZ and ANTHONY J. VALENTE
I. Introduction 287
II. Initial Events in the Pathogenesis of Atherosclerosis 288
III. Mechanisms Leading to Progression: The Transitional Lesion 294
IV. The Mature or Complex Lesion 296
V. Atherosclerosis: A Substrate for Clinical Events 298
VI. Risk Factors and Atherogenesis 298
VII. Conclusions 299
References 300
11. Antioxidant Protection of Low-Density Lipoprotein and Its Role
in the Prevention of Atherosclerotic Vascular Disease
JOHN F. KEANEY, JR., and BALZ FREI
I. Introduction 303
II. Mechanisms of LDL Oxidation 305
III. Antioxidant Protection of LDL 315
IV. Antioxidant Protection of Lipoprotein (a) 326
V. Small-Scale Clinical Trials of LDL Antioxidant Protection 327
VI. Alternative Mechanisms of Antioxidant Action 335
VII. Conclusions 338
References 339
12. Antioxidants as Antiatherogens: Animal Studies
SEAN M. LYNCH and BALZ FREI
I. Introduction 353
II. Antiatherogenic Effects of Antioxidants
in Experimental Animals 354

III. Summary and Conclusions 376
References 376
13. Natural Antioxidants and Cardiovascular Disease:
Observational Epidemiologic Studies and Randomized Trials
J. MICHAEL GAZIANO, JOANN E. MANSON, and CHARLES H. HENNEKENS
I. Introduction 387
II. Descriptive Studies 388
III. Case-Control Studies 391
IV. Prospective Cohort Studies 393
V. Limitations of Observational Epidemiologic Data 40 I
VI. Randomized Trials 402
VII. Conclusions 405
References 406
14. Myocardial Ischemia-Reperfusion Injury and the
Cardioprotective Potential ofNatural Antioxidants
DAVID R.JANERO
I. The Disease State of Myocardial Ischemia-Reperfusion 41 I
II. Oxidative Stress and the Pathogenesis of Myocardial
Ischemia-Reperfusion Injury 415
III. The Clinical Significance of (Oxidative) Myocardial
Ischemia-Reperfusion Injury 420
IV. Natural Antioxidants as Cardioactive Agents
against Ischemia-Reperfusion Injury 421
V. Therapy with (Natural) Antioxidants for Myocardial
Ischemia-Reperfusion Injury? 430
References 432
IV. Immunity and Infection

15. Role of Antioxidants in the Maintenance ofImmune Functions
ADRIANNE BENDICH
I. Introduction 447
II. Free Radicals and Antioxidants 447
III. Immune Responses 448
IV. Risk Factors for Increased Exposure to Free Radicals,
and/or Lowered Antioxidant Status:
Effects on Immune Responses 449

V. Summary and Conclusions 460
References 462
16. Ascorbic Acid in Neutrophils
MARK LEVINE, KULDEEP R. DHARIWAL, YAOHUI WANG,
JAE B. PARK, and RICHARD W. WELCH
I. Introduction and Experimental Limitations 469
II. Ascorbate Accumulation 470
III. Ascorbate and Neutrophil Function 475
IV. Summary 482
References 484
17. Oxidants and Antioxidants in Viral Diseases:
Metabolic Regulation and Autotoxicity
ERNST PETERHANS
I. Introduction 489
II. In Vitro Studies of Viral Pathogenesis 490
III. In Vivo Studies of Viral Pathogenesis 496
IV. Infections with Human and Simian Lentiviruses 50 I
V. Is There a Case for Antioxidants in the Therapy
of Viral Diseases? 503
VI. Conclusions 506
References 507

v. Cataracts, Neurological Disorders,

and Exercise
18. Relationships between Natural Antioxidants
and Cataract Formation
PAUL F. JACQUES, LEO T. CHYLACK, JR., and ALLEN TAYLOR
I. Normal Lens and Age-Related Cataract 515
II. Prevalence of Cataract and Related Disability:
Public Health Impact 516
III. Oxidation and Cataract Formation 517
IV. Natural Antioxidants and Prevention of Cataract 519
V. Summary 527
References 529

19. Vitamin E and Other Antioxidants in Neurological
Function and Disease
DAVID P. R. MULLER
I. Introduction 535
II. Antioxidant Deficiency 536
III. Increased Concentrations of Reactive Oxygen Species 546
IV. Summary and Conclusions 556
References 558
20. The Role of Vitamin E and Other Antioxidants
in Physical Exercise
LESTER PACKER, ABRAHAM Z. REZNICK, and SHARON LANDVIK
I. Introduction 567
II. Physiological Effects of Exercise and Possible Mechanisms
of Exercise-Induced Free Radical Generation 567
III. Antioxidant Defenses 569
IV. Summary 574
References 575
Index 577

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