Antioxidants in Disease Mechanisms and Therapy

, by August; Murad; Anders; Coyle; Packer

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ISBN: 9780120329397 | 0120329395
Cover: Hardcover
Copyright: 10/9/1996

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Antioxidants in Disease Mechanisms and Therapy presents molecular actions of natural and synthetic antioxidants and emphasizes the potential role in disease mechanisms and therapeutic strategies. The modulationof gene expression by the induction of antioxidant enzymes is a novel role beyond the direct antioxidant action. The volume explores the current state of knowledge on oxidants and antioxidants in disease processes, including arteriosclerosis, adult respiratory distress syndrome, cystic fibrosis, Down's syndrome, inflammation, cataract, age-related macular degeneration, afflications of the nervous system, AIDS, liver diseases, diabetes, skin diseases, and cancer. Key Features * Contains cutting-edge information on focused topics written by expert scientists * Provides the first in-depth treatment of novel compounds, such as melatonin and polyamines * Attempts molecular pathophysiology which links basic science and the clinic * Presents critical assessment of controversial topics

Contributors

xvii

(6)

Preface

xxiii

PART I Natural Antioxidants

(164)

Antioxidants: The Basics--What They Are and How to Evaluate Them

(18)

Barry Halliwell

I. Introduction

(3)

II. Biologically Relevant ROS/RNS

(10)

III. Proving That a Putative Antioxidant Is Important in Vivo

(1)

References

(4)

Metabolism of Vitamin C in Health and Disease

(28)

Ann M. Bode

I. Introduction and Overview

(1)

II. Changes in Vitamin C Status Associated with Disease

(2)

III. Mechanism of Changes in Vitamin C Status Associated with Disease

(11)

IV. Evidence for Therapeutic Effectiveness of Vitamin C

(4)

V. Significance and Conclusions

(1)

References

(9)

Regulation of Human Plasma Vitamin E

(16)

Maret G. Traber

I. Introduction

(1)

II. Plasma Kinetics

(2)

III. Discrimination between Tocopherols

(2)

IV. Genetic Studies

(4)

V. Conclusions

(1)

References

(6)

Glutathione and Glutathione Delivery Compounds

(14)

Mary E. Anderson

I. Glutathione

(5)

II. Glutathione Delivery Compounds

(4)

III. Summary

(1)

References

(5)

XXX-Lipoic Acid: A Metabolic Antioxidant and Potential Redox Modulator of Transcription

(24)

Lester Packer

Sashwati Roy

Chandan K. Sen

I. Introduction

(1)

II. Role of Lipoate in Metabolism

(5)

III. Antioxidant Properties

(6)

IV. NF-(k)B Role in Normal and Abnormal Cell Function

(5)

References

(7)

Antioxidant Actions of Melatonin

103

(16)

Russel J. Reiter

I. Introduction

103

(1)

II. Melatonin as a Free Radical Scavenger

104

(3)

III. Melatonin as an Antioxidant

107

(6)

IV. Effect of Melatonin on Enzymes Related to the Antioxidative Defense System

113

(1)

V. Concluding Remarks

114

(1)

References

115

(4)

Antioxidative and Metal-Chelating Effects of Polyamines

119

(32)

Erik Lovaas

I. Introduction

119

(2)

II. Chemistry and Type Reactions of Polyamines

121

(7)

III. Antioxidative Effects of Polyamines

128

(12)

IV. Conclusions

140

(1)

References

141

(10)

Antioxidant and Chelating Properties of Flavonoids

151

(16)

Ludmila G. Korkina

Igor B. Afanas'ev

I. Introduction

151

(1)

II. Free Radical-Scavenging, Antioxidant, and Chelatory Activities of Flavonoids

152

(4)

III. Prooxidant Activity of Flavonoids

156

(1)

IV. Cytotoxic Effects of Flavonoids against Tumor Cells

157

(2)

V. Mutagenic and Antimutagenic Properties of Flavonoids

159

(1)

References

159

(8)

PART II Synthetic Antioxidants and Enzyme Mimics

167

(106)

Potential Use of Iron Chelators against Oxidative Damage

167

(38)

Jean-Baptiste Galey

I. Introduction

167

(2)

II. Iron Homeostasis

169

(3)

III. Iron Release during Oxidative Stress

172

(4)

IV. Iron Chelators

176

(15)

V. Protective Effect of Iron Chelators against Oxidative Damage

191

(4)

VI. Concluding Remarks

195

(1)

References

196

(9)

N-Acetylcysteine: Pharmacological Considerations and Experimental and Clinical Applications

205

(24)

Ian A. Cotgreave

I. Introduction

205

(1)

II. Biopharmaceutical and Pharmacological Aspects

206

(3)

III. General Biochemical and Cellular Effects

209

(4)

IV. Specific Therapeutic Effects of NAC in Animals and Humans

213

(8)

V. Summary

221

(1)

References

221

(8)

Ebselen as a Glutathione Peroxidase Mimic and as a Scavenger of Peroxynitrite

229

(18)

Helmut Sies

Hiroshi Masumoto

I. Introduction

229

(1)

II. Synthesis of Ebselen

230

(1)

III. Molecular Activities of Ebselen

230

(6)

IV. Activity in Biological Model Systems

236

(2)

V. Metabolism

238

(1)

VI. Clinical Assessment

239

(1)

VII. Other Selenoorganic Compounds

240

(1)

VIII. Concluding Remarks

240

(1)

References

241

(6)

Salen-Manganese Complexes: Combined Superoxide Dismutase/Catalase Mimics with Broad Pharmacological Efficacy

247

(26)

Susan R. Doctrow

Karl Huffman

Catherine B. Marcus

Wael Musleh

Annadora Bruce

Michel Baudry

Bernard Malfroy

I. Introduction

247

(2)

II. Multiple Catalytic Activities of EUK-8, a Prototype SOD/Catalase Mimic

249

(7)

III. Efficacy of EUK-8 in Experimental Models for Disease

256

(8)

IV. Conclusions and Future Directions

264

(1)

References

265

(8)

PART III Antioxidant Enzyme Induction and Pathophysiology

273

(152)

Antioxidant Drug Targeting

273

(20)

Anthony C. Allison

I. Introduction

273

(1)

II. Delivering Antioxidants to Organs or Tissues

274

(2)

III. Targeting Antioxidants to Particular Cell Types

276

(1)

IV. Effects of Antioxidants on Enzymes

277

(2)

V. Reactive Oxygen Intermediates as Signal Transducers

279

(2)

VI. Effects of Antioxidants on Transcription Factors

281

(3)

VII. Effects of Antioxidants on Gene Expression

284

(4)

VIII. Discussion

288

(1)

References

289

(4)

Antioxidant-Inducible Genes

293

(36)

Thomas Primiano

Thomas R. Sutter

Thomas W. Kensler

I. Introduction

293

(1)

II. Genes Induced by Antioxidants

294

(13)

III. Mechanisms of Gene Induction by Antioxidants

307

(8)

IV. Consequences of Antioxidant Gene Induction

315

(2)

V. Future Perspectives

317

(1)

References

317

(12)

Redox Signaling and the Control of Cell Growth and Death

329

(32)

Garth Powis

John R. Gasdaska

Amanda Baker

I. Introduction

329

(1)

II. Cellular Redox Systems

330

(5)

III. Redox Targets

335

(5)

IV. Cellular Responses to Redox Changes

340

(9)

V. Conclusion

349

(1)

References

349

(12)

Protective Action of Nitrone-Based Free Radical Traps against Oxidative Damage to the Central Nervous System

361

(18)

Robert A. Floyd

I. Introduction

361

(1)

II. CNS Is Sensitive to Oxidative Damage

362

(1)

III. Spin-Trapping Reactions of Nitrone-Based Free Radical Traps

363

(1)

IV. Antioxidant Activity of PBN

364

(1)

V. PBN Exhibits Protective Activity in Septic Shock Models

365

(1)

VI. PBN and Related Compounds Are Neuroprotective

365

(1)

VII. Pharmacology Studies of PBN and Related Compounds

366

(1)

VIII. PBN Prevents LPS-Mediated NO Formation in Liver

367

(1)

IX. NO Chemistry and Its Potential Neurotoxic Action

368

(2)

X. Hypothesis to Explain the Neuroprotective Action of PBN

370

(4)

References

374

(5)

Reactive Oxygen Species and Their Contribution to Pathology in Down Syndrome

379

(24)

Judy B. de Haan

Ernst J. Wolvetang

Francesca Cristiano

Rocco Iannello

Cecile Bladier

Michael J. Kelner

Ismail Kola

I. Introduction

379

(2)

II. Sodl and Gpxl Expression Levels in Down Syndrome

381

(2)

III. Premature Aging of Down Syndrome Individuals

383

(8)

IV. Apoptosis and Down Syndrome

391

(6)

V. Conclusion and Discussion

397

(1)

References

398

(5)

Antioxidants, Redox-Regulated Transcription Factors, and Inflammation

403

(22)

Paul G. Winyard

David R. Blake

I. Background

403

(3)

II. Two Redox-Controlled Transcription Factors: AP-I and NF-(k)B

406

(3)

III. ROI/RNI and NF-(k)B in Human Diseases

409

(1)

IV. Ischemic-Reperfusion Injury, Rheumatoid Arthritis, and Redox-Regulated Transcription Factors

410

(1)

V. NF-(k)B and Anti-inflammatory Drugs

411

(1)

VI. What Is the Cellular Source of ROI Involved in NF-(k)B Activation?

412

(4)

VII. Conclusion

416

(1)

References

416

(9)

PART IV Disease Processes

425

(252)

Relationships among Oxidation of Low-Density Lipoprotein, Antioxidant Protection, and Atherosclerosis

425

(32)

Hermann Esterbauer

Reinhold Schmidt

Marianne Hayn

I. Introduction

425

(2)

II. The Low-Density Lipoprotein Oxidation Hypothesis

427

(4)

III. Assessment of Oxidation Resistance of Low-Density Lipoprotein

431

(3)

IV. Vitamin E Supplementation Increases Oxidation Resistance of Low-Density Lipoprotein as Judged by the Conjugated Diene Method

434

(3)

V. Plasma Low-Density Lipoprotein Antioxidant Levels

437

(3)

VI. Epidemiological Studies

440

(7)

VII. Conclusion

447

(1)

References

448

(9)

Adult Respiratory Distress Syndrome: A Radical Perspective

457

(34)

Samuel Louie

Barry Halliwell

Carroll Edward Cross

I. Introduction

457

(3)

II. Pathobiologic Considerations

460

(12)

III. Therapeutic Strategies

472

(8)

IV. Conclusion

480

(1)

References

481

(10)

Oxidative Stress in Cystic Fibrosis: Does It Occur and Does It Matter?

491

(25)

Albert van der Vliet

Jason P. Eiserich

Gregory P. Marelich

Barry Halliwell

Carroll E. Cross

I. Introduction

491

(1)

II. Role of Oxygen-Derived Species

492

(2)

III. Oxidative Stress and Lung Disease

494

(1)

IV. Evidence for Oxidative Stress in Cystic Fibrosis

494

(3)

V. The Special Case of XXX-Carotene Deficiency

497

(1)

VI. Oxidative Stress at the Airway Surface

498

(2)

VII. Potential Role of Nitric Oxide and Related Species in Cystic Fibrosis

500

(3)

VIII. Other Considerations

503

(1)

IX. Potential for Antioxidant Therapy

503

(1)

X. Dilemma of Administering Aerosolized Thiols or Ascorbic Acid

504

(1)

XI. Conclusion

505

(1)

References

505

(11)

Oxidative Stress and Antioxidant Function in Relation to Risk for Cataract

516

(21)

Allen Taylor

Thomas Nowell

I. Introduction

516

(1)

II. Public Health Issues Regarding Cataract

517

(1)

III. Clinical Features of Cataract

518

(1)

IV. Oxidation, Smoking, and Cataract Formation

518

(1)

V. Associations between Antioxidants and Cataract

519

(12)

VI. Conclusions

531

(1)

References

532

(5)

The Macular Pigment: A Possible Role in Protection from Age-Related Macular Degeneration

537

(20)

John T. Landrum

Richard A. Bone

Mark D. Kilburn

I. Introduction

537

(1)

II. The Macular Pigment

538

(3)

III. Age-Related Macular Degeneration

541

(1)

IV. Methods

542

(5)

V. Results

547

(4)

VI. Discussion and Conclusions

551

(2)

References

553

(4)

Neurological Disease

557

(24)

David P. R. Muller

I. Introduction

557

(1)

II. Antioxidant Deficiency

558

(5)

III. Increased Concentrations of Reactive Oxygen Species

563

(9)

IV. Conclusions

572

(1)

References

572

(9)

Role of Cysteine and Glutathione in HIV Infection and Cancer Cachexia: Therapeutic Intervention with N-Acetylcysteine

581

(20)

Wulf Droge

Andrea Gross

Volker Hack

Ralf Kinscherf

Michael Schykowski

Michael Bockstette

Sabine Mihm

Dagmar Galter

I. Introduction

581

(2)

II. Elevated Venous Plasma Glutamate Levels as an Early and Possibly Universal Marker for Catabolic and Precatabolic Conditions

583

(2)

III. "Push" and "Pull" Mechanisms in Catabolic and Precatabolic Processes

585

(4)

IV. Immunological Implications

589

(3)

V. Therapeutic Intervention with a Cysteine Derivative: Effects of Long-Term Treatment with N-Acetylcysteine

592

(3)

VI. Concluding Remarks

595

(1)

References

596

(5)

Role of Oxidative Stress and Antioxidant Therapy in Alcoholic and Nonalcoholic Liver Diseases

601

(28)

Charles S. Lieber

I. Metabolism of Ethanol

601

(9)

II. Acetaldehyde: Its Metabolism and Toxicity, Including Peroxidation

610

(1)

III. Antioxidant Therapy

611

(7)

IV. Summary

618

(1)

References

619

(10)

Antioxidant Therapy for the Prevention of Type I Diabetes

629

(10)

Birgit Heller

Volker Burkart

Eberhard Lampeter

Hubert Kolb

I. Introduction

629

(1)

II. Mechanism of Reactive Oxygen Intermediates and Nitric Oxide Toxicity

630

(2)

III. Intervention Studies in Animals

632

(2)

IV. Intervention Studies in Humans

634

(1)

V. Concluding Remarks

635

(1)

References

635

(4)

Photoaging of the Connective Tissue of Skin: Its Prevention and Therapy

639

(18)

Karin Scharffetter-Kochanek

I. Introduction

639

(1)

II. The Nature of Photoaging

640

(2)

III. Role of Ultraviolet-Generated Oxygen Species in Cutaneous Photoaging

642

(5)

IV. Prevention and Therapy of Connective Tissue Damage

647

(3)

References

650

(7)

Antioxidant Nutrients and Cancer Incidence and Mortality: An Epidemiologic Perspective

657

(20)

Susan T. Mayne

I. Introduction

657

(2)

II. Antioxidant Nutrients and Cancer Prevention

659

(7)

III. Antioxidant Nutrients and Cancer Survival

666

(2)

IV. Antioxidants and Cancer: Emerging Issues

668

(2)

V. Conclusions and Policy Implications

670

(1)

References

671

(6)

Index

677

(16)

Contents of Previous Volumes

693

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