
Molecular Basis of Oxidative Stress
Chemistry, Toxicology, Disease Pathogenesis, Diagnosis, and Therapeutics
By: Frederick A. Villamena (Editor), Henry Jay Forman (Editor)
Hardcover | 23 January 2025 | Edition Number 2
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560 Pages
27.94 x 21.59 x 3.18
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In-depth resource on mechanisms of oxidative stress and damage and the role of free radicals in disease, diagnosis, and therapeutics
Molecular Basis of Oxidative Stress is a comprehensive resource on the molecular and chemical bases of oxidative stress, providing insight on various diseases caused by oxidative stress (cancer, cardiovascular, neurodegenerative) and the role of reactive oxygen species (ROS) in disease pathogenesis along with in-depth knowledge about the mechanisms of oxidative stress and damage, free radical chemistry, and the role of free radicals in disease, diagnosis, and therapeutics.
Thoroughly updated and expanded to reflect advances in the years since its original publication, the Second Edition includes new chapters covering topics like oxidative stress mechanisms, biomarkers, and therapeutic strategies in the management and treatment of diseases. The disease section features 10 new emerging diseases, including kidney and eye diseases and COPD.
This Second Edition also covers developments in the field in the last several years, such as an increase in mortality rate from air pollution and obstructive pulmonary diseases in which exogenous oxidants are initiators.
Written by a team of highly qualified academics, Molecular Basis of Oxidative Stress discusses sample topics including:
- Classification, physico-chemical properties, sources, and detection of reactive species and etiology of COPD from cigarette smoke and pollution
- Oxidative, reductive and indirect non-redox modifications of key biomolecular systems such as lipids, proteins, and DNA by reactive species
- Gene expression of antioxidant defense enzymes, mitochondrial dysfunction and aberrant activation of NOX and cell signaling
- Biomarkers of oxidative stress in neurodegenerative diseases and emerging fields inbiomarker discovery such as cysteinylated albumin and nitroalkene fatty acids
Imparting strong foundational knowledge of redox chemistry, chemistry of oxidative damage and mechanisms of oxidative stress, and oxidative stress-mediated disease pathogenesis, Molecular Basis of Oxidative Stress is an essential reference for both novice and advanced toxicologists, biochemists, and pharmacologists, along with clinical and medical scientists in various fields such as oncology, cardiovascular, andneuroscience.
List of Contributors xxi
Preface to Second Edition xxix
Preface First Edition xxxi
1 Chemistry of Reactive Species 1
Frederick A. Villamena
1.1 Redox Chemistry, 1
1.2 Classification of Reactive Species, 2
1.3 Reactive Oxygen Species, 4
1.4 Reactive Nitrogen Species, 15
1.5 Reactive Sulfur and Chlorine Species, 18
1.6 Reactivity, 23
1.7 Origins of Reactive Species, 27
1.8 Methods of Detection, 32
2 Lipid Peroxidation and Nitration 49
Sean S. Davies and Lilu Guo
2.1 Peroxidation of PUFAs, 49
2.2 Cyclic Endoperoxides and Their Products, 52
2.3 Fragmented Products of Lipid Peroxidation, 58
2.4 Epoxy Fatty Acids, 62
2.5 Lipid Nitrosylation, 62
3 Protein Posttranslational Modification 71
James L. Hougland, Joseph Darling, and Susan Flynn
3.1 Oxidative Stress-Related PTMs: Oxidation Reactions, 71
3.2 Amino Acid Modification by Oxidation-Produced Electrophiles, 80
3.3 Detection of Oxidative-Stress Related PTMs, 81
3.4 Role of PTMs in Cellular Redox Signaling, 84
4 DNA Oxidation 93
Dessalegn B. Nemera, Amy R. Jones, and Edward J. Merino
4.1 The Context of Cellular DNA Oxidation, 93
4.2 Oxidation of Oligonucleotides, 94
4.3 Examination of Specific Oxidative Lesions, 96
5 Cellular Antioxidants and Phase 2 Proteins 113
Yunbo Li
5.1 Definitions, 113
5.2 Roles in Oxidative Stress, 113
5.3 Molecular Regulation, 117
5.4 Induction in Chemoprevention, 119
5.5 Inactivation, 119
5.6 Conclusions and Perspectives, 121
6 Mitochondrial Dysfunction 129
Yeong-Renn Chen and Chwen-Lin Chen
6.1 Mitochondria and Submitochondrial Particles, 129
6.2 Energy Transduction, 131
6.3 Mitochondrial Stress, 132
6.4 Superoxide Anion Radical Generation as Mediated by ΔPH, Δψ, ETC, and Disease Pathogenesis, 133
7 NADPH Oxidases: Structure and Function 147
Mark T. Quinn
7.1 Introduction, 147
7.2 Phagocyte NADPH Oxidase Structure, 147
7.3 Phagocyte ROS Production, 152
7.4 Phagocyte NADPH Oxidase Function, 155
7.5 Nonphagocyte NADPH Oxidase Structure, 156
7.6 Nonphagocyte ROS Production, 161
7.7 Functions of Nonphagocyte NADPH Oxidases, 162
8 Cell Signaling and Transcription 189
Imran Rehmani, Fange Liu, and Aimin Liu
8.1 Common Mechanisms of Redox Signaling, 189
8.2 Redox and Oxygen-Sensitive Transcription Factors in Prokaryotes, 191
8.4 Oxygen Sensing in Metazoans, 200
8.5 Medical Significance of Redox and Oxygen-Sensing Pathways, 204
9 Oxidative Stress and Redox Signaling in Carcinogenesis 213
Rodrigo Franco, Aracely Garcia-Garcia, Thomas B. Kryston, Alexandros G. Georgakilas, Mihalis I. Panayiotidis, and Aglaia Pappa
9.1 Redox Environment and Cancer, 213
9.2 Oxidative Modifications to Biomolecules and Carcinogenesis, 217
9.3 Measurement of Oxidative DNA Damage in Human Cancer, 223
9.4 Epigenetic Involvement in Oxidative Stress-Induced Carcinogenesis, 223
9.5 Deregulation of Cell Death Pathways by Oxidative Stress in Cancer Progression, 226
10 Neurodegeneration from Drugs and Aging-Derived Free Radicals 247
Annmarie Ramkissoon, Aaron M. Shapiro, Margaret M. Loniewska, and Peter G. Wells
10.1 ROS Formation, 247
10.2 Protection against ROS, 273
10.3 Nrf2 Regulation of Protective Responses, 279
11 Cardiac Ischemia and Reperfusion 321
Murugesan Velayutham and Jay L. Zweier
11.1 Oxygen in the Heart, 321
11.2 Sources of ROS during Ischemia and Reperfusion, 322
11.3 Modulation of Substrates, Metabolites, and Cofactors during I-R, 326
11.4 ROS-Mediated Cellular Communication during I-R, 328
11.5 ROS and Cell Death during Ischemia and Reperfusion, 329
11.6 Potential Therapeutic Strategies, 330
12 Atherosclerosis: Oxidation Hypothesis 339
Chandrakala Aluganti Narasimhulu, Dmitry Litvinov, Xueting Jiang, Zhaohui Yang, and Sampath Parthasarathy
12.1 Lipid Peroxidation, 339
12.2 Oxidation Hypothesis of Atherosclerosis, 340
12.3 Animal Models of Atherosclerosis, 341
12.4 Aldehyde Generation from Peroxidized Lipids, 343
13 Cystic Fibrosis 355
Neal S. Gould and Brian J. Day
13.1 Lung Disease Characteristics in CF, 355
13.2 Role of CFTR in the Lung, 358
13.3 Oxidative Stress in the CFTR-Deficient Lung, 358
13.4 Antioxidant Therapies for CF, 361
14 Cigarette Smoking and Air Pollution 369
Andrew J. Ghio and Urmila Kodavanti
14.1 Exposure to Cigarette Smoke, 369
14.2 Air Pollution Particles, 371
14.3 Ozone, 374
14.4 Nitrogen and Sulfur Oxides, 374
14.5 Interaction between PM and Oxidant Gases, 375
14.6 Oxidative Stress and Mechanistic Pathways of Disease After Exposure to Air Pollutants, 375
15 Oxidative Stress in Chronic Obstructive Pulmonary Disease 381
Peter J. Barnes
15.1 Introduction, 381
15.2 Increased Oxidative Stress in COPD, 382
15.3 Effects of Oxidative Stress in COPD, 384
15.4 Strategies for Reducing Oxidative Stress, 386
15.5 Conclusions 389
16 Oxidative Stress in the Eye 395
Annie K. Ryan, Wade W. Rich, Peter A. Jansen, Megan M. Allyn, Katelyn E. Swindle-Reilly, and Matthew A. Reilly
16.1 Introduction, 395
16.2 The Cornea, 396
16.3 The Lens, 400
16.4 The Vitreous Humor, 403
16.5 The Retina and Optic Nerve, 404
16.6 Therapeutic Approaches to ROS Elevation in the Eye, 407
16.7 Conclusion, 408
17 The Role of Oxidative Stress in Chronic Kidney Disease (CKD) 417
Ara Aboolian, Jordan Younes, Alejandra Romero, Jay C. Jha, Karin Jandeleit-Dahm, and Jaroslawna Meister
17.1 Introduction, 417
17.2 Sources of Oxidative Stress in CKD, 419
17.3 Mechanisms by Which Oxidative Stress Contributes to CKD, 421
17.4 Interplay Between Oxidative Stress and Senescence in CKD, 423
17.5 Treatment Options for CKD, 423
18 Biomarkers of Oxidative Stress in Neurodegenerative Diseases 437
Rukhsana Sultana, Giovanna Cenini, and D. Allan Butterfield
18.1 Introduction, 437
18.2 Biomarkers of Protein Oxidation/Nitration, 439
18.3 Biomarkers of Lipid Peroxidation, 441
18.4 Biomarkers of Carbohydrate Oxidation, 444
18.5 Biomarkers of Nucleic Acid Oxidation, 445
19 Cysteinylated Albumin as Oxidative Stress Biomarker and Therapeutic Target 455
Alessandra Altomare, Giulio Vistoli, Cristina Banfi, and Giancarlo Aldini
19.1 Introduction, 455
19.2 Cellular and Extracellular Thiols Distribution, 455
19.3 HSA and CYS34, 456
19.4 CYS34 Reactivity and Reactions, 458
19.5 CYS34 Oxidized Forms in Physio-Pathological Conditions, 460
19.6 Endogenous Regulation of Intracellular and Extracellular Thiol-Redox Homeostasis, 462
19.7 Molecular and Therapeutic Strategies for Reversing Mercaptalbumin from the Oxidized Forms, 462
19.8 Conclusion, 464
20 Nitroalkene Fatty Acids: Formation, Metabolism, Reactivity, and Signaling 469
Martina Steglich, Martin Sosa, Francisco J. Schopfer, and Lucia Turell
20.1 Introduction, 469
20.2 Diet and Fatty Acids, 469
20.3 Nitroalkene Fatty Acids in Vivo Formation, 470
20.4 Metabolism and Distribution, 471
20.5 Reactivity of Nitroalkene Fatty Acids, 472
20.6 Nitroalkylation as A Protein Post-Translational Modification, 473
20.7 Nitrooleic Acid and Disease, 475
20.8 Concluding Remarks, 477
21 Synthetic Antioxidants 483
Gregory Durand
21.1 Endogenous Enzymatic System of Defense, 483
21.2 Metal-Based Synthetic Antioxidants, 484
21.3 Nonmetal-Based Antioxidants, 488
21.4 Nitrones, 495
References, 504
Index 513
ISBN: 9781119790266
ISBN-10: 1119790263
Published: 23rd January 2025
Format: Hardcover
Language: English
Number of Pages: 560
Audience: Professional and Scholarly
Publisher: John Wiley & Sons Inc (US)
Country of Publication: GB
Edition Number: 2
Dimensions (cm): 27.94 x 21.59 x 3.18
Weight (kg): 1.58
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