Oxidative Stress and Antioxidant Protection E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Oxidative Stress and Antioxidant Protection: The Science of Free Radical Biology and< Disease provides an overview of the basic principles of free radical formation. The text delves into free radical formation in molecular biology and its effect on subcellular damage, as well as the role of antioxidant reserves as a protective mechanism. Oxidative Stress and Antioxidant Protection begins with a historical perspective of pioneers in oxidative stress with an introductory section that explains the basic principles related to oxidative stress in biochemistry and molecular biology, demonstrating both pathways and biomarkers. This section also covers diagnostic imaging and differential diagnostics. The following section covers psychological, physiologic, pharmacologic and pathologic correlates. This section addresses inheritance, gender, nutrition, obesity, family history, behavior modification, natural herbal-botanical products, and supplementation in the treatment of disease. Clinical trials are also summarized for major medical disorders and efficacy of treatment, with particular focus on inflammation, immune response, recycling, disease progression, outcomes and interventions. Each of the chapters describes what biomarker(s) and physiological functions may be relevant to a concept of specific disease and potential alternative therapy. The chapters cover medical terminology, developmental change, effects of aging, senescence, lifespan, and wound healing, and also illustrates cross-over exposure to other fields. The final chapter covers how and when to interpret appropriate data used in entry level biostatistics and epidemiology. Authored and edited by leaders in the field, Oxidative Stress and Antioxidant Protection will be an invaluable resource for students and researchers studying cell biology, molecular biology, and biochemistry, as well professionals in various health science fields.
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Veröffentlichungsjahr: 2016
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Table of Contents
Cover
Title Page
Copyright
List of contributors
Special recognition
Foreword
Preface
Section I: Introduction
Chapter 1: Introduction to free radicals, inflammation, and recycling
Historical perspective
Oxidative stress concept
Free radicals
Inflammatory pathways
Mitochondria
Educational redox
References
Chapter 2: Diagnostic imaging and differential diagnosis
Diagnostic method in clinical practice
Biomarkers in biological investigation
Biological imaging
Multiple choice questions
References
Section II: Clinical Correlations on Acute and Chronic Diseases
Chapter 3: Free radicals: their role in brain function and dysfunction
Introduction
The beneficial role of oxidative stress in the brain
The harmful role of oxidative stress in the brain
The role of oxidative stress (OS) in programmed neuronal death (apoptosis)
Oxidative stress in neonatal hypoxic-ischemic encephalopathy (HIE)
OS in inflammatory brain disease due to infection
OS in neuroimmunological disorders
OS in cerebrovascular disease
OS in traumatic brain injury
OS in neurodegenerative disorders
Alzheimer disease
OS in Parkinson disease (PD)
Therapeutic implications and opportunities
Multiple choice questions
Additional Reading
Chapter 4: Mediators of neuroinflammation
Introduction
Cells mediating neuroinflammation
Characteristics of microglial activation
Neuron–microglia interplay
Pathological implications of dysregulated microglial activation
Microglial activation as a diagnostic biomarker and therapeutic target
Multiple choice questions
References
Chapter 5: Oxidative and nitrative stress in schizophrenia
Introduction
Oxidative stress and psychiatric disorders
Biomarkers of oxidative stress in schizophrenia
Reactive nitrogen species in the central nervous system
Nitrative stress in schizophrenia
Role of glutathione in schizophrenia
Antioxidants
Nitric oxide and antipsychotics in schizophrenia
Concluding remarks
Multiple choice questions
References
Chapter 6: The effects of hypoxia, hyperoxia, and oxygen fluctuations on oxidative signaling in the preterm infant and on retinopathy of prematurity
Introduction
Anatomy and physiology of the human eye in adult and development
Premature birth
Oxygen and oxidative stress
Human ROP phases
The role of oxygen in ROP
Link between oxidative stress and oxygen in ROP
Clinical applications
Conclusions
Multiple choice questions
References
Chapter 7: Oxidative damage in the retina
Introduction
The vitreous
The retina
Age-related macular degeneration
Diabetic retinopathy
Multiple choice questions
References
Chapter 8: The role of oxidative stress in hearing loss
Introduction
Age-related hearing loss
Noise-induced hearing loss
Drug-induced hearing loss
Summary and conclusions
Multiple choice questions
References
Chapter 9: Disorders of children
Introduction – reactive oxygen species, antioxidative systems, and oxidative stress
Biomarkers for oxidative stress
Nitric oxide system blockade, endothelial dysfunction, and oxidative stress
Pregnancy as a state of oxidative stress
Prenatal disorders
Oxidative stress in fetal-to-neonatal transition
Evaluation of oxidative stress status in neonates using specific biomarkers
Breast milk – a rich source of antioxidants
Oxidative stress biomarkers in pediatric medicine
Infectious and inflammatory disorders (especially acute encephalopathy)
Redox modulation strategy for severe influenza encephalopathy
Summary and conclusions
Acknowledgments
Multiple choice questions
References
Chapter 10: Oxidative stress in oral cavity: interplay between reactive oxygen species and antioxidants in health, inflammation, and cancer
Oxidative stress – significance for oral and general environment
Reactive oxygen species – general outline
Oxidative stress – damage to cellular structures
Oxidative stress and antioxidants – implications in general and oral diseases
Multiple choice questions
References
Chapter 11: Oxidative stress and the skin
Introduction
Mechanisms of oxidative stress in the skin
Reactive oxygen species
Skin aging
Skin cancer
Vitiligo
Intrinsic defenses against free radicals
Topical antioxidants
Drug-induced skin photosensitization
Conclusion
Multiple choice questions
References
Chapter 12: Oxidative stress in osteoarticular diseases
Introduction
Rheumatoid arthritis
Osteoarthritis
Osteoporosis
Acknowledgments
Multiple choice questions
References
Chapter 13: Gene therapy to reduce joint inflammation in horses
Introduction
Animal model considerations
The nature and origins of horses
Pathobiology of joint disease
Current therapy for traumatic arthritis
Development of gene therapy in horses
Gene selection
Delivery system
Studies developing gene therapy for arthritis
Multiple choice questions
References
Chapter 14: Muscle and oxidative stress
Vitamins E and C and oxidative stress in muscle
Muscular disease and nutrition
Multiple choice questions
References
Chapter 15: Role of oxidants and antioxidants in male reproduction
Introduction
Male infertility: an oxidative role
Methods used to measure OS and TAC
Physiological role of ROS in reproductive system
Pathological roles of ROS in male reproduction
Antioxidants
Antioxidants: a therapeutic approach
Conclusion and key points
Multiple choice questions
References
Chapter 16: Role of oxidants and antioxidants in female reproduction
Introduction
Reactive oxygen species
Characteristics of reactive nitrogen species, physiological roles, and mechanisms of damage
Antioxidants
Antioxidant treatment for female infertility
Methods of detection of ROS in the female
Physiological roles and sources of ROS
Factors contributing to oxidative stress in the female
Pathological effects and associations of oxidative stress
Conclusion and key points
Multiple choice questions
References
Chapter 17: Reactive oxygen species, oxidative stress, and cardiovascular diseases
Introduction
Impact of oxidative stress on pathogenesis of hypertension
Impact of oxidative stress on pathogenesis of atherosclerosis
Impact of oxidative stress on pathogenesis of ischemia/reperfusion injury
Impact of oxidative stress on pathogenesis of cardiac arrhythmia
Multiple choice questions
References
Chapter 18: Oxidative stress and antioxidant imbalance: respiratory disorders
Summary
Introduction
Respiratory infections
Airway diseases
Interstitial lung diseases
Asbestosis and lung cancer
Pulmonary arterial hypertension
Respiratory muscle dysfunction
Role of antioxidants in the management of lung diseases
Multiple choice questions
References
Chapter 19: Oxidative stress and type 1 diabetes
Introduction
Role of
β
-cell oxidative stress in T1D
Genetics of
β
cell sensitivity and resistance to ROS
ROS and autoimmunity in T1D
NADPH oxidase and T1D
Conclusions
Multiple choice questions
References
Chapter 20: Metabolic syndrome, inflammation, and reactive oxygen species in children and adults
Introduction
The biology of insulin resistance
The consequences of hyperinsulinism
The consequences of inadequate insulinization
Inflammation and the liver: prooxidant hepatocellular damage
Diabetes and reactive oxygen species
Conclusion
Multiple choice questions
References
Chapter 21: Oxidative stress in chronic pancreatitis
Summary
Introduction
Pancreas, chronic pancreatitis (CP), and symptoms
CP-induced production of oxidative stress
Alcoholic pancreatitis and oxidative stress
Environmental factors induction of ROS/RNS production, pancreatic inflammation, and cellular injuries
Application of antioxidants in amelioration of ROS/RNS-mediated pancreatic inflammation
Phytochemicals as chemoprevention regimen against CP
Conclusion
Multiple choice questions
References
Chapter 22: Wound healing and hyperbaric oxygen therapy physiology: oxidative damage and antioxidant imbalance
Introduction
Hyperbaric oxygen environment
Wound environment
Conclusion
Multiple choice questions
References
Chapter 23: Radiobiology and radiotherapy
A brief history of radiation therapy
Mechanism of radiation
Biology in cancer
4 R's: repair, redistribution, reoxygenation, and repopulation
The impact of free radicals
The role of oxygen in clinical radiation therapy
Hyperbaric oxygen
High linear energy transfer radiation
Neutrons in radiotherapy
Protons in radiotherapy
Chemical radiosensitizers
Conclusion
Multiple choice questions
References
Chapter 24: Chemotherapy-mediated pain and peripheral neuropathy: impact of oxidative stress and inflammation
Introduction
History of chemotherapy-induced peripheral neuropathy
Pathways involved in CIPN
Classes of chemotherapy associated peripheral neuropathy
Induction of peripheral neuropathy
Classifications of CIPN based on the severity
Amelioration of pain: current status
Summary and conclusions
Multiple choice questions
References
Chapter 25: Grape polyphenol-rich products with antioxidant and anti-inflammatory properties
Bioactive compounds in grape, wine, and wine by-products: phenolic compounds
Antioxidant and anti-inflammatory properties of grape extracts
Conventional and alternative solvent extraction processes
Concentration and purification
Conclusions
Multiple choice questions
References
Chapter 26: Isotonic oligomeric proanthocyanidins
Introduction
The discovery of OPCs
The characteristics of OPCs
The health-promoting properties of OPCs
Dosage and safety
Why isotonic?
Multiple choice questions
References
Chapter 27: Superoxide dismutase mimics and other redox-active therapeutics
Introduction – redoxome
Superoxide dismutases
What is an SOD mimic?
Design of an SOD mimic – introduction
Phase I. Mimicking the thermodynamics and kinetics of enzymatic dismutation establishes the first lead and efficacious SOD mimic – MnTE-2-PyP
5+
Phase II. Improving the Mn porphyrin bioavailability – third lead compound MnTnHex-2-PyP
5+
was identified
Phase III. Suppressing the toxicity of amphiphilic MnTnHex-2-PyP
5+
– fourth lead compound MnTnBuOE-2-PyP
5+
was identified
The activities of SOD mimics other than catalysis of dismutation
Interaction with signaling proteins and other cellular proteins
Which type of reaction(s) will an SOD mimic undergo
in vivo
?
Therapeutic effects of Mn porphyrins
Other SOD mimics
Is therapeutic efficacy proportional to SOD-like activity of SOD mimics?
Redox-active synthetic compounds other than SOD mimics
Redox-active natural compounds
Purity of drugs
Pharmacokinetics and bioavailability of redox-active drugs and SOD mimics
Summary
Acknowledgment
Multiple choice questions
References
Chapter 28: Herbal medicine: past, present, and future with emphasis on the use of some common species
Early Islamic herbal medicine
Ayurvedic, siddha, and traditional Chinese medicine
Present eminence of herbal medicine
Curcuma longa
, Zingiberacease
Nigella sativa
Zinzibar officinale
(Zingiberaceae, ginger)
Future potential of herbal medicine
Multiple choice questions
References
Chapter 29: Ayurvedic perspective on oxidative stress management
Ayurveda
Basic concepts of Ayurveda
Role of oxidative stress in disease development: Ayurvedic perspective
Pathophysiological basis of oxidative stress in Ayurveda
Ayurvedic management of oxidative stress
Current advances
Multiple choice questions
References
Chapter 30: Clinical trials and antioxidant outcomes
Introduction
Pathophysiology of oxidative pathways
Clinical trials
Clinical implications of research findings
Limitations of current clinical trials
Summary points
Multiple choice questions
References
Chapter 31: Statistical approaches to make decisions in clinical experiments
Introduction, preliminaries, and basic components of statistical decision-making mechanisms
R: statistical software
Likelihood
Tests on means of continuous data
The exact likelihood ratio test for equality of two normal populations
Empirical likelihood
Receiver operating characteristic curve analysis
Goodness-of-fit tests
Wilcoxon rank-sum tests
Tests for independence
Numerical methods for calculating critical values and powers of statistical tests
Concluding remarks
Appendix
Multiple choice questions
References
Webliographies
Index
End User License Agreement
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Guide
Cover
Table of Contents
Foreword
Preface
Section I: Introduction
Begin Reading
List of Illustrations
Chapter 1: Introduction to free radicals, inflammation, and recycling
Figure 1.1 Homeostasis is a balance between levels of free radicals (FR) and antioxidants (AOX).
Figure 1.2 Oxidative stress starts a cascade that can lead to chronic disease if not modified by corrective actions.
Figure 1.3 Free radicals (FR) are key to initiation and propagation of the paths that lead to disease. Antioxidants (AOX) are key to protection.
Chapter 2: Diagnostic imaging and differential diagnosis
Figure 2.1 Electroretinogram waveform.
t
0
is the time of light stimulus,
t
a
is the time to the peak of the negative deflection and
t
b
is the time to the peak of the positive deflection. A wave is the amplitude of the negative deflection, mainly from the photoreceptor cell depolarization; B wave is the amplitude of the positive deflection from the neurosensory retinal response to the photoreceptor cell depolarization. Times vary with species, but are generally in the 10–300 ms range. Amplitudes also vary widely, but are in the 20–500 mV range.
Figure 2.2 Simple mass spectrogram of methane. The less abundant
13
C is hidden in the
12
C peaks except for
13
C
1
H
4
visible right of
12
C
1
H
4
peak.
Chapter 3: Free radicals: their role in brain function and dysfunction
Figure 3.1 The early and late cascade of events leading to nerve cell death in neonatal HIE.
Chapter 4: Mediators of neuroinflammation
Figure 4.1 Interplay between neuronal injury and microglial activation and the various mediators of neuroinflammation. TNF-α, tumor necrosis factor alpha; TACE, TNF-α converting enzyme; IL-1β, interleukin-1 beta; ICE, IL-1β converting enzyme; IL-1RA, interleukin-1 receptor antagonist; ROS, reactive oxygen species; NOX, NADPH oxidase; NO, nitric oxide; iNOS, inducible nitric oxide synthase; PGs, prostaglandins; COX, cyclooxygenase; HSP60, heat shock protein 60; MMP3, matrix metalloproteinase 3; siRNA, small interfering RNA.
Chapter 5: Oxidative and nitrative stress in schizophrenia
Figure 5.1 The predominance of oxidation processes caused by oxidative stress. (Figure prepared by A. Dietrich-Muszalska.)
Figure 5.2 Nitric oxide (NO) and peroxynitrite (ONOO
−
) syntheses; cNOS – cellular NOS. (Figure prepared by A. Dietrich-Muszalska.)
Figure 5.3 NO involvement in nitrative stress. (Figure prepared by A. Dietrich-Muszalska.)
Chapter 6: The effects of hypoxia, hyperoxia, and oxygen fluctuations on oxidative signaling in the preterm infant and on retinopathy of prematurity
Figure 6.1 Anatomy of the eye and vasculature. (Drawing by James Gilman, CRA, FOPS.)
Figure 6.2 Oxyhemoglobin dissociation curve depicting oxygen saturations with fetal and adult hemoglobin. (Drawing by James Gilman, CRA, FOPS.)
Figure 6.3 VEGF dilemma: retinal vascular development requires VEGF. (Drawing by James Gilman, CRA, FOPS.)
Figure 6.4 Subunits of NADPH oxidase and activation. The isoform NOX4 does not require aggregation with cytoplasmic subunits and becomes activated when it aggregates with p22phox. (Drawing by James Gilman, CRA, FOPS.)
Chapter 7: Oxidative damage in the retina
Figure 7.1 The rod photoreceptor cell (PRC) outer segment is the top Figure and the retinal pigment epithelial (RPE) cell is the bottom Figure The active form of rhodopsin visual pigment is an outer segment disk membrane-bound protein that absorbs light causing a conformational shift in the 11-
cis
-retinal (11-
cis
-RAL) moiety to all-
trans
-retinal (all-
trans
-RAL), resulting in cleavage of all-
trans
-RAL and opsin protein that stimulates the photoreceptor to trigger a neuronal impulse through a cyclic GMP pathway. The all-
trans
-RAL aldehyde is reduced to all-
trans
-retinol (all-
trans
-ROL) by an NADPH-dependent retinal dehydrogenase (RDH). The all-
trans
-ROL is transported through the interphotoreceptor matrix and into the RPE through a partially understood mechanism involving specific retinal-binding proteins in the interphotoreceptor matrix and in the RPE microsome. The all-
trans
-ROL is esterified by lecithin retinol acyltransferase to a fatty acid all-
trans
-retinyl ester, which then aggregates in a specialized microsome called a retinosome. RPE65 isomerase then hydrates the all-
trans
-retinyl ester and changes the ROL to the 11-
cis
-isomer and a free fatty acid. An NAD
+
-dependent retinal dehydrogenase oxidizes the 11-
cis
-ROL to 11-
cis
–RAL, which is then transported back to the membrane-bound apo-opsin where the two are covalently joined to form the activated rhodopsin, 11-
cis
-RAL-opsin.
Chapter 9: Disorders of children
Figure 9.1 Oxidative stress biomarkers in exhaled breath (“lung biomarkers”). Abbreviations: ADMA, asymmetric dimethylarginine; CO, carbon monoxide; NO, nitric oxide.
Figure 9.2 Effects of chronic nitric oxide blockade on oxidative stress status in young rats.
8, 9
Abbreviations: Cr, creatinine; L-NAME,
N
G
-nitro-L-arginine methyl ester; 8-OHdG, 8-hydroxy-2′-deoxyguanosine. Presented data are mean values of the markers. Oral administration of L-NAME (20, 50, and 80 mg/dl of drinking water), but not aminoguanidine (400 mg/dl), for 4 weeks of induced systemic hypertension and a significant reduction in urinary excretion of nitrite/nitrate. Rats treated with L-NAME also showed a significant increase in urinary 8-OHdG excretion compared with the control animals. The above effects were dependent on the dosage of L-NAME. The effects of L-NAME (50 mg/dl) on blood pressure and urinary nitrite/nitrate and 8-OHdG were restored by a large dose of L-arginine (2.0 g/dl), a precursor for nitric oxide synthesis.
Figure 9.3 Oxidative stress status in the fetoplacental unit. Increased generation of reactive oxygen species during growth of the fetoplacental unit is a prominent feature of pregnancy. Further enhancement of oxidative stress is likely to promote several pregnancy-related disorders including preeclampsia, fetal growth restriction, preterm labor, and low birthweight.
Figure 9.4 Correlations between oxidative stress biomarkers (total antioxidative capacity (TAC), thioredoxin-1) and clinical data (maternal body weight, body mass index).
16
Figure 9.5 Correlations between oxidative stress biomarkers (total hydroperoxides (TH), total antioxidative capacity (TAC), oxidative stress index (OSI), thioredoxin-1) and neonatal birthweight.
16
Figure 9.6 Urinary levels of acrolein-lysine, 8-hydroxy-2′-deoxyguanosine, and nitrite/nitrate in 1-month-old term and preterm neonates.
29
Abbreviations: Cr, creatinine; 8-OHdG, 8-hydroxy-2′-deoxyguanosine. Presented data are mean values of the markers. (a) Group 1: healthy term neonates (
n
= 10); Group 2a: stable preterm neonates (
n
= 21); Group 2b: sick preterm neonates (
n
= 16). *
p
< 0.05 versus Group 1, Group 2a. (b) In Group 2b, neonates developing active retinopathy exhibited significantly higher levels of acrolein-lysine than the other neonates without retinopathy did. *
p
< 0.05 versus sick preterm neonates without retinopathy.
Figure 9.7 Age-related changes of urinary levels of acrolein-lysine (a), 8-hydroxy-2′-deoxyguanosine, pentosidine, and nitrite/nitrate (b) in healthy children.
37
Abbreviations: Cr, creatinine; 8-OHdG, 8-hydroxy-2′-deoxyguanosine. Presented data are mean values of the markers. Note that younger subjects exhibit higher levels of urinary markers.
Figure 9.8 Mechanisms of brain damage in influenza-associated acute encephalopathy (IAE).
38
The findings presented in recent reports suggest that, in cases of severe IAE, either seasonal or 2009 pandemic, pathological manifestations similarly result from complex biological phenomena including overproduction of cytokines/chemokines and nitric oxide/reactive oxygen species, apoptosis induction, and vascular endothelial disruption. Additional exploration of these pathways is expected to contribute to the development of more effective adjunctive strategies in IAE.
Chapter 10: Oxidative stress in oral cavity: interplay between reactive oxygen species and antioxidants in health, inflammation, and cancer
Figure 10.1 Interplay between reactive oxygen species and antioxidants.
Figure 10.2 Oxidative stress and its involvement in several major diseases.
Figure 10.3 Generation of different reactive oxygen species.
Figure 10.4 Methods for determination of oxidative stress.
Chapter 11: Oxidative stress and the skin
Figure 11.1 A 69-year-old man presented with a 25-year history of gradual, asymptomatic thickening and wrinkling of the skin on the left side of his face. The physical examination showed hyperkeratosis with accentuated ridging, multiple open comedones, and areas of nodular elastosis. Histopathological analysis showed an accumulation of elastolytic material in the dermis and the formation of milia within the vellus hair follicles. Findings were consistent with the Favre–Racouchot syndrome of photodamaged skin, known as dermatoheliosis. The patient reported that he had driven a delivery truck for 28 years. Ultraviolet A (UVA) rays transmit through window glass, penetrating the epidermis and upper layers of dermis. Chronic UVA exposure can result in thickening of the epidermis and stratum corneum, as well as destruction of elastic fibers. This photoaging effect of UVA is contrasted with photocarcinogenesis. Although exposure to ultraviolet B (UVB) rays is linked to a higher rate of photocarcinogenesis, UVA has also been shown to induce substantial DNA mutations and direct toxicity, leading to the formation of skin cancer. The use of sun protection and topical retinoids and periodic monitoring for skin cancer were recommended for the patient. (Image from
The New England Journal of Medicine
, Jennifer Gordon and Joaquin Brieva, Unilateral dermatoheliosis, 366; 16 Copyright ©2012 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.)
Figure 11.2 DNA damage: a central event in skin cancer. DNA damage is central to altered cell proliferation, differentiation, DNA repair, cell death, and immune system function required for skin cancer development. Exogenously and endogenously derived ROS (e.g., OH−. and H
2
O
2
) induce mutations in growth regulatory genes (e.g., p21 ras, p53) and can disrupt normal immune system function. The effects of ROS result in abnormal cellular physiology that contribute to elevated ROS (e.g., increased SOD activity), thus maintaining the DNA damage cycle, and the potential for cancer-causing events to occur.
Chapter 12: Oxidative stress in osteoarticular diseases
Figure 12.1 Effects of oxidative stress on chondrocytes and cartilage. ECM, extracellular matrix.
Figure 12.2 General mechanism of aging and bone damage produced by oxidative stress. UFA, unsaturated fatty acid.
Chapter 13: Gene therapy to reduce joint inflammation in horses
Figure 13.1 Normal and osteoarthritic synovium and cartilage transfected with scAAV packaged with genome coding for fluorescent green protein 10 days postinjection.
Chapter 15: Role of oxidants and antioxidants in male reproduction
Figure 15.1 Primary, secondary, and tertiary types of reactive oxygen species, including the reactive nitrogen species.
Figure 15.2 Potential generators of reactive oxygen species leading to oxidative stress in the male comprise endogenous and exogenous sources. Physiological levels of reactive oxygen species play a role in sperm capacitation, acrosome reaction, hyperactivation, and sperm–oocyte binding. However, at pathological levels, reactive oxygen species causes lipid peroxidation, DNA damage, and apoptosis, which lead to detrimental effects on male fertility.
Figure 15.3 Accumulation of reactive oxygen species and the depletion of endogenous antioxidants bring about a state of oxidative stress, which could result in lipid peroxidation and damaged mitochondrial and nuclear DNA.
Figure 15.4 Reactive oxygen species (superoxide anion, hydrogen peroxide, and hydroxyl radical) are generated from oxidative processes in the plasma membrane and mitochondria of the male gamete. These reactions involve the SOD and catalase antioxidant enzymes along with copper and iron, respectively.
Chapter 16: Role of oxidants and antioxidants in female reproduction
Figure 16.1 c-Jun N terminal kinase pathway and apoptosis. ROS act as secondary messengers that activate core apoptotic pathways via the activation of the c-Jun N-terminal kinase.
Figure 16.2 The consequences of ROS and oxidative stress. Exposure to pathological levels of ROS and oxidative stress causes cellular membrane and DNA damage along with protein manipulation.
Figure 16.3 Antioxidant supplementation efficacy as a therapeutic intervention. The efficacy of antioxidant supplementation as a therapeutic intervention remains inconclusive at this stage. The outcomes of studies involving intervention with oral antioxidant supplementation either support its use in alleviating the damaging effects of oxidative stress or show no effects on the reproductive parameters studied (selected studies are shown here).
Figure 16.4 Factors contributing to oxidative stress in the female reproductive system. Factors that contribute to the generation of oxidative stress in the female reproductive system include obesity, malnutrition, alcohol intake and smoking, misuse of drugs such as marijuana and cocaine, and exposure to environmental toxins.
Figure 16.5 Pregnancy complications and oxidative stress. Complications that may arise from oxidative stress conditions include recurrent pregnancy loss, spontaneous abortions, and preeclampsia.
Chapter 17: Reactive oxygen species, oxidative stress, and cardiovascular diseases
Figure 17.1 Pathogenesis of atherosclerosis.
Chapter 19: Oxidative stress and type 1 diabetes
Figure 19.1 ROS participate in multiple stages during T1D development. (1) ROS directly induce β-cell dysfunction; (2) ROS facilitate programmed β-cell death; (3) ROS produced by macrophage directly induce β-cell destruction. (4) ROS promote CD4
+
T-cell proliferation and secretion of inflammatory cytokines, which further induce β-cell damage. (5) During CD8
+
T-cell activation, ROS participate in antigen cross-presentation from dendritic cells to CD8
+
T cells. (6) CD8
+
T cells destroy β cells through perforin, granzyme, and FasL–Fas pathways. ROS facilitate β-cell damage in all these pathways.
Chapter 20: Metabolic syndrome, inflammation, and reactive oxygen species in children and adults
Figure 20.1 Common characteristics of the metabolic syndrome include centripetal obesity, dysglycemia, dyslipidemia, and hyperuricemia (detectable in the patient's plasma), hypertension, liver disease [non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH)], gout [manifested as pain in the great toe (podagra)], acanthosis nigricans and atherosclerotic cardiovascular disease (ASCVD), stroke, and peripheral vascular disease that can predispose to gangrene.
Figure 20.2 Insulin binds to the insulin receptor to initiate signaling. Second messengers cause alternations in metabolism (e.g., increased glycolysis and glycogen synthesis and suppressed gluconeogenesis) and the movement of the insulin-responsive glucose transporter (GLUT4) from the cytoplasmic pool to the plasma membrane facilitating glucose uptake into the skeletal muscle and adipose tissue.
Figure 20.3 This Figure illustrates the delivery of free fatty acids (FFAs) from the omentum to the liver via the portal circulation. The omentum and adipose tissue secrete IL-1, IL-6, TNF-α, and resistin, whereas adiponectin secretion is deficient.
Chapter 22: Wound healing and hyperbaric oxygen therapy physiology: oxidative damage and antioxidant imbalance
Figure 22.1 Monoplace chamber using compressed 100% oxygen.
Figure 22.2 Multiplace chamber using compressed air and 100% oxygen hood.
Figure 22.3 Acute wound healing is an orderly process. Interruption of this process leads to prolonged inflammation and a vicious cycle of further injury and continued inflammation. Breaking this chronic wound cycle requires diligent intervention at multiple points.
Chapter 23: Radiobiology and radiotherapy
Figure 23.1 Radiation effect on DNA.
Figure 23.2 Cell cycle and cell cycle checkpoints.
Chapter 24: Chemotherapy-mediated pain and peripheral neuropathy: impact of oxidative stress and inflammation
Figure 24.1 As a result of chemotherapeutic regimen: (1) calcium overload ensues, secondary to Na and Ca channel activation, resulting in calpain activation and proteolysis of the cytoskeletal (e.g., microtubules and neurofilaments). Calpain activity may also activate NF-κB; (2) downstream generation of inflammatory cytokines, NO, and exacerbation of ROS production from mitochondria, and increased Ca release; (3) this is aggravated by the attendant activation of glia (astrocytes and microglia) and immune effectors [see text for details]. Successful intervention to ameliorate NF-κB-induced pathology and oxidative stress would improve the efficacy and dosing regimens with chemotherapeutics. DRG = dorsal root ganglia.
Chapter 25: Grape polyphenol-rich products with antioxidant and anti-inflammatory properties
Figure 25.1 Chemical structures of main phenolic compounds present in grapes and wines.
Figure 25.2 Beneficial effects of grape and grape-derived products.
Figure 25.3 General signaling mechanisms associated with inflammatory processes.
Chapter 26: Isotonic oligomeric proanthocyanidins
Figure 26.1 Oxidative stress contributes to many diseases.
Figure 26.2 OPC is an electron donor that regenerates vitamins C and E and has direct action on hydroxyl and lipid radicals.
Figure 26.3 Antioxidants provide electrons which prevent ROS reactions with vital cell components. OPCs also help regenerate vitamin C, vitamin E, vitamin A, indirectly neutralizing FRs to terminate corresponding chain reactions and the consequent vicious cycle.
Figure 26.4 OPC protects the cardiovascular system through reduction of inflammation.
Figure 26.5 An isotonic liquid formulation provides much better absorption of OPC than other formulations.
10
(Vijayalakslakshmi Nandakumar and Santosh K. Katiyar 2008. Reproduced with permission.)
Chapter 27: Superoxide dismutase mimics and other redox-active therapeutics
Figure 27.1 Cellular metabolism is redox controlled. Listed are some of the major metabolic pathways that involve electron shuttling among biomolecules. Some of the electron shuttling would eventually, intentionally (supporting signaling pathways) or not (such as mitochondrial respiration at complexes I and III where electron from ubiquinol would hit the surrounding oxygen and reduce it one-electronically to ), give rise to reactive oxygen, nitrogen, sulfur, selenium, and chlorine species (RS). Endogenous antioxidative defenses, for example, catalase, families of superoxide dismutases (SOD), glutathione peroxidases (GPx), and peroxyredoxins, are in charge of maintaining low nanomolar levels of reactive species (RS), that is, physiological redox environment (Figure 27.2).
If levels of RS increase, as a consequence of cellular injury, a cascade of signaling events are upregulated with the goal to restore normal redox environment. Redox-active pathways along with reactive species and endogenous low- and high-molecular antioxidants are now recognized as
redoxome and define cellular redox environment.
Redoxome is as critical for cell metabolism as are proteome and genome.
Figure 27.2 Redox-active molecules, reactive species, and antioxidants. Redox-active molecules/species (some of them listed here) and their involvement in redox-based pathways comprise the cellular redoxome. Redoxome is maintained by oxidation/reduction reactions, that is, electron shuttling; it is only natural that redox-active drugs may be best suited to restore it when perturbed in diseases.
Figure 27.3 In addition to the electron transport chain, several other metabolic pathways (some of which are listed here) produce superoxide and subsequently its progeny and contribute to oxidative stress. The production via such pathways is enhanced if redox environment is perturbed. Some enzymes would produce superoxide under pathological conditions such as family of nitric oxide synthases (NOS), and some would produce under both pathological and physiological conditions such NADPH oxidases. For example, family of nitric oxide synthases produces
•
NO under physiological conditions; yet in the absence of reducing equivalents (tetrahydrobiopterin) such as in case of oxidative stress, they would produce . Under oxidative stress and with excessive
•
NO production, the action of cytochrome oxidase complex IV, the terminal enzyme of ETC, may be blocked due to the nitrosylation of the Fe protoporphyrin active site.
Figure 27.4 The involvement of superoxide in the production of some of the major reactive species contributing to oxidative stress. Dismutation of leads to the formation of peroxide, a major signaling and damaging species, maintained under physiological conditions at nanomolar levels. With any free low-molecular weight Fe
2+
species around (e.g., aqua or carboxylato complexes), H
2
O
2
will produce the most oxidizing, yet shortly-lived hydroxyl radical
•
OH. When
•
OH is formed in the vicinity of nucleic acids (RNA and DNA), the major oxidative damage will occur. By the action of myeloperoxidase, H
2
O
2
will produce another strongly oxidizing hypochlorous acid, which is under physiological conditions in equilibrium with deprotonated and reactive form, ClO
−
. would react with
•
NO at diffusion-limited rates of >10
9
M
−1
s
−1
to form highly damaging peroxynitrite, predominantly in ONOO
−
form.
12
ONOO
−
would
in vivo
make an adduct with CO
2
, which would decompose to form two highly oxidizing radicals, and
•
NO
2
.
Figure 27.5 MnP-based “true” SOD mimics, that is, compounds that catalyze dismutation with
k
cat
() higher than
k
for self-dismutation of ∼5 × 10
5
M
−1
s
−1
at pH 7.
13
Figure 27.6 SOD mimics other than Mn porphyrins. Only “true” metal-bearing SOD mimics are listed referring to compounds that catalyze dismutation with
k
cat
() higher than
k
for self-dismutation of ∼5 × 10
5
M
−1
s
−1
at pH 7.
13
The structures of Fe porphyrins, Mn and Fe corroles, Mn cyclic polyamine, M40403 (GC4403), water-soluble fullerene, and Mn salen EUK-207 (of cyclic structure that enhances its stability toward loss of Mn) are shown. Metal salts, for example, those of Mn, Ce, and Os, are also potent SOD mimics. Cerium dioxide comes in a form of ceria nanoparticles. While very potent SOD mimic in aqueous setting (
k
cat
as high as that of SOD enzyme), the OsO
4
is too toxic for therapeutic purposes. The Mn
2+
ion ligated with different low-molecular weight ligands is a fair SOD mimic; yet its clinical development might be precluded due to the neurotoxicity described as manganism.
15–17
Figure 27.7 (a) Crystal structure of human erythrocyte catalase (PDB ID: 1QQW), and (b) crystal structure of human cytochrome P450 (PDB ID: 2F9Q) and their active sites. Pictures are created with Cn3D 4.3.1.
26–28
Porphyrin is a macrocyclic ring that encapsulates metal; in turn, it affords the highest stability to a metal complex, assuring no loss of metal where reactions of interest occur. It is only natural that such ligand has been used by nature for numerous proteins and enzymes, such as myoglobin, guanylyl cyclase, oxidases, oxygenases, prolyl hydroxylases, catalase, cytochrome P450 family of enzymes, and so on. For the same reason, we have chosen to modify a metalloporphyrin structure to be efficient catalyst for dismutation.
Figure 27.8 Phase I of the design of porphyrin-based SOD mimic started from nonsubstituted Mn phenyl- and pyridylporphyrins, Mn(III)
meso-tetrakis-
phenylporphyrin, MnTPP
+
, and Mn(III)
meso-tetrakis
(pyridinium-2 (3 or 4)-yl)porphyrins, MnT-2(3 or 4)-PyP
+
. In these complexes, Mn is in its +3 oxidation state and is bound to four pyrrolic nitrogens.
24
Two of these form coordinated bonds with Mn – sharing the electrons with Mn. The other two nitrogens are deprotonated and are thus negatively charged and in turn provide one electron each to neutralize Mn 3+ charge. Consequently, one charge is left on Mn
3+
center in a resting state. The appropriate thermodynamics and kinetics for the catalysis of dismutation has been adjusted by alkylation of the pyridyl nitrogens with alkyl carbocations. In turn, the nitrogens end up carrying cationic charges. Those charges pull the electron density from the Mn site, making it electron deficient and in turn ready to accept electrons from anionic in the first step of dismutation process. Moreover, the charges impose favorable electrostatics attracting anionic superoxide. Electrostatics accounts for ∼2 orders of magnitude in the value of
k
cat
().
2, 23
Figure 27.9 The design of porphyrin-based SOD mimics. Starting from unsubstituted MnT-4-PyP
+
(Figure 27.8), the pyridyl nitrogens were first alkylated giving rise to
para
analog MnTM-4-PyP
5+
with fair SOD-like activity. To enhance electron-withdrawing effects, the nitrogens were then moved closer to the metal site from
para
into
ortho
positions. The MnTM(E)-2-PyP
5+
, the first lead, was synthesized. It is still the most frequently studied compound.
2, 23
Based on
ortho
pyridyl porphyrin, the imidazolyl analog (Figure 27.5) was subsequently synthesized and became the second lead – MnTDE-2-ImP
5+
. In order to improve the bioavailability of highly charged compounds, the alkyl chains were then lengthened and the third lead, MnTnHex-2-PyP
5+
was synthesized. Adapted from ref 216.
Figure 27.10 The substitutions of the porphyrin ring aimed to develop potent SOD mimics. Different substitutions were done on different
meso
and
beta
positions of porphyrin core. Also the carbons were replaced with nitrogens at
beta
and
meso
positions. The porphyrins of shrunken core, that is, corroles, and those of extended core, that is, porphycenes were synthesized by us and others also.
Figure 27.11 Structure–activity relationships for Mn porphyrins. The three structure–activity relationships were established between the
E
1/2
for Mn
III
P/Mn
II
P redox couple and for Mn porphyrins that have either cationic charges on periphery (triangles), anionic charges on periphery (circles), or no charges on periphery (open squares). All complexes have +1 charge on metal site in resting (stable) state, that is, Mn +3 oxidation state. Few compounds have Mn in +2 oxidation state in resting state, that is MnBr
8
TM-3(or 4)PyP
4+
. Adapted from ref 216.
Figure 27.12 The impact of electrostatics on dismutation. The electrostatic effects account for differences of more than two orders of magnitude in the catalysis of dismutation. The difference is higher between the porphyrins that are cationic (MnTE-2-PyP
5+
) and anionic (MnBr
8
TSPP
3−
) (400-fold) than is between the Mn porphyrins that are cationic (MnTE-2-PyP
5+
) and neutral (MnBr
8
T-2-PyP
+
) on the periphery (130-fold).
43
Figure 27.13 The impact of charge distribution on the SOD-like activity of MnP-based SOD mimics. The charge distribution contributed to 220-fold difference in
k
cat
() between compounds that appear similar on the first sight (with same number and types of atoms in their structures), with five-membered rings attached at
meso
positions. While both compounds bear two nitrogen atoms and three carbon atoms in each of their five-membered rings, those rings are differently organized. Different organization in turn results in different proximity of five positive charges to Mn site and in markedly different SOD-like activities.
70
Figure 27.14 Phases of the design of Mn porphyrin-based SOD mimics. In phase I, the critical impact of
ortho
cationic charges on the was recognized. This feature was then preserved in all subsequent analogs while the nature of pyridyl substituents was modified to optimize bioavailability and toxicity. In phase II, the lipophilicity of MnTE-2-PyP
5+
was enhanced, the MnTnHex-2-PyP
5+
was synthesized. Its enhanced efficacy, due in major part to its orders of magnitude higher accumulation within cell and mitochondria, overcomes its increased toxicity. The higher toxicity is, at least in part, due to its higher cellular accumulation. In phase III, the insertion of oxygen atoms into alkyl chains suppressed the toxicity in MnTnBuOE-2-PyP
5+
relative to MnTnHex-2-PyP
5+
without reducing the lipophilicity of the molecule. Adapted from ref 216.
Figure 27.15 The reactivity of Mn porphyrin-based SOD mimics toward different reactive species. Thus far, the reactivity toward , ONOO
−
, , ClO
−
,
•
NO, HNO, and H
2
O
2
was assessed for many Mn porphyrins. The data were published or reported at meetings.
2, 23
The data on and ONOO
−
are given in Table 27.1. The most potent SOD mimics, such as MnTE-2-PyP
5+
, have rate constant with somewhat higher than with ONOO
−
. The reactions with ClO
−
occur with similar rate constants to those with ONOO
−
.
2, 25, 85
While not listed here, the MnP-based SOD mimics are also reactive toward lipid-reactive species; no quantification is available. The reactivities toward thiols, simple and protein thiols, and toward ascorbate HA
−
has been quantified in part.
2, 40, 83, 86–91, 213, 214
Figure 27.17 Differential role of peroxide in the mechanism(s) of action(s) of Mn porphyrins in cancer versus normal cell. Cancer cell is already under oxidative stress and is vulnerable to any additional increase in it. This is frequently due to the perturbed balance between SOD enzymes and H
2
O
2
-removing enzymes, which results in high H
2
O
2
levels. The sensitivity to additional increase in oxidative stress has been employed in reactive species-producing cancer treatments such as radio- and chemotherapy, Normal cell has a variety of endogenous antioxidants to fight oxidative stress unless overwhelming. Most recent data indicate higher MnP levels in tumor than in normal tissue.
214,215
Thus, given higher H
2
O
2
and MnP levels, the yield of the reactions of the MnP in cancer and normal cells is differential and results in cancer cell death vs normal cell healing. The p50 and p65 are NF-κB subunits; p65-S-S-G and p50-S-S-G are glutathionylated subunits; cys p65 and cys p50 relate to cysteines of p50 and p65 subunits; complexes I, III, and IV are complexes of mitochondrial respiration; GSH, glutathione; NOS, nitric oxide synthase; GPx, glutathione peroxidase; TrxR, thioredoxin reductase; Prx, peroxiredoxin; HA
−
, monodeprotonated physiologically relevant form of ascorbic acid. The Nrf2/Keap1 pathway, which controls levels of endogenous antioxidative defenses, seems to be involved. For details on pathways listed, please refer to Forum Issue of
Antioxid Redox Signal
on “SOD therapeutics”, 2014.
88, 127, 128, 216
Figure 27.16 The role of H
2
O
2
in MnP-related cellular pathways. The most potent SOD mimics are able to oxidize a number of biological molecules (those studied thus far are listed here) in the presence of H
2
O
2
. AO, ascorbate oxidation; TO, thiol oxidation; TPx, thiol peroxidation; NAD-ox, NAD oxidation; NADP-ox, NADP oxidation; L-ox, lipid oxidation; L-Px, lipid peroxidation. Adapted from ref 216.
Figure 27.18 The interaction of SOD mimics with key cellular proteins. Only some of them are listed. The knowledge on new interactions emerges constantly. The interactions with HIF-1α, AP-1, SP-1, and NF-κB were demonstrated with several classes of SOD mimics (see manuscripts published in 2014, Forum Issue on “SOD Therapeutics”).
2, 122, 127, 132–135
The action upon Nrf2/Keap1 (with subsequent upregulation of numerous endogenous antioxidative defense systems, some of which are indicated here) has been reported with Mn(II) cyclic polyamine, nitroxide, and natural product curcumin. While the Nrf2/Keap1 was not directly assessed as a result of treatment with MnTnHex-2-PyP
5+
, the upregulation of most of the listed enzymes was seen in kidney ischemia/reperfusion rat model; the impact was enhanced when MnP was given along with
N
-acetylcysteine – H
2
O
2
producing system.
136, 137
The action upon protein thiols is direct, while the actions on other pathways may be indirect and waits further exploration.
86, 88
The inhibition of Na
+
/H
+
exchanger (NHE in this Figure only, otherwise normal hydrogen electrode) was shown in rat streptozotocin diabetes nephropathy model.
130
Adapted from ref 2.
Figure 27.19 Major classes of diseases where Mn porphyrin-based SOD mimics were successfully tested. Studies are done on cells, rodents, and nonhuman primates. Pulmonary radioprotection was tested on nonhuman primates.
146
More detailed list of diseases was provided in Refs.
2, 22, 25
. Some of the therapeutic effects of other drugs are listed in several review manuscripts.
2, 22, 25, 127, 133, 147
Figure 27.20 Structure–activity relationship between the and
E
1/2
for redox couple involved (dashed line for Mn
III
P/Mn
II
P and dotted line for Mn
IV
P/Mn
III
P). The relationship fits best for metal complexes and is not that good for nonmetal-based compounds such as nitroxides; its ability to affect superoxide dismutation is related to the fairly high rate constant for the reaction of nitroxide with protonated superoxide, very little of which is present at physiological pH. It seems that perhaps two relationships exist for two different redox couples and are slightly shifted based on different energetics of electron transfers involved with those couples. The maximum of the bell shape of the SAR describes the potential at which both steps of dismutation process occur at similar rates and where the
k
cat
() is in turn maximal. For those compounds that use Mn
III
P/Mn
II
P redox couple, at more negative potentials, the metal +3 oxidation state is stabilized and cannot be reduced with to start the dismutation process. At more positive potentials, Mn is stabilized in +2 oxidation state and cannot be oxidized with in the first step of dismutation process. For those compounds that use Mn
IV
P/Mn
III
P redox couple, such as corroles and biliverdins, the reverse is true. The first step would involve the oxidation of the metal site from Mn
3+
to Mn
4+
and the reduction of followed by reduction of metal to Mn +3 oxidation resting state with concomitant oxidation of . To identify the compounds reader is directed to Table 27.1. Adapted from ref 2.
Figure 27.21 Other redox-active therapeutics. Listed are compounds that are not able to both reduce and oxidize . Yet, during redox cycling, they can still affect
in vivo
levels of by removing it via oxidizing or reducing it. Due to its high oxidizing power, some compounds can be oxidized with ONOO
−
and cycle back with cellular reductants or perhaps other species (e.g., MnTBAP
3−
or AEOL11207).
Figure 27.22 Natural compounds that exhibit therapeutic effects. Some of those are attributed incorrectly to the SOD-like activity.
118
Chapter 28: Herbal medicine: past, present, and future with emphasis on the use of some common species
Figure 28.1 Molecular structures of some biologically active components in
Cucuma longa except paclitaxel is in Taxus brevifolia.
Figure 28.2 Molecular structures of some components in
Nigella sativa.
Figure 28.3 Molecular structures of some of the components of ginger.
Chapter 31: Statistical approaches to make decisions in clinical experiments
Figure 31.1 Screenshot of the R interface.
Figure 31.2 R data analysis output for measurements of HDL cholesterol levels (mg/dl) in healthy individuals.
Figure 31.3 Histogram of the differences in the number of acute care visits pre- and post-asthma training.
Figure 31.4 R data analysis output for measurements of HDL cholesterol levels (mg/dl)
X
and
Y
in the disease and healthy individuals, respectively.
Figure 31.5 ROC curves related to the biomarkers. The solid diagonal line corresponds to the ROC curve of biomarker
A
, where and . The dashed line displays the ROC curve of biomarker
B
, where and . The dotted line close to the upper left corner plots the ROC curve for biomarker
C
, where and .
Figure 31.6 The nonparametric estimators of ROC curves of three different biomarkers based on samples of sizes 1000. The solid diagonal line corresponds to the nonparametric estimator of the ROC curve of biomarker
A
, where and . The dashed line displays the nonparametric estimator of the ROC curve of biomarker
B
, where and . The dotted line close to the upper left corner plots the nonparametric estimator of the ROC curve for biomarker
C
, where and .
List of Tables
Chapter 1: Introduction to free radicals, inflammation, and recycling
Table 1.1 Biomarkers for oxidative stress
Chapter 4: Mediators of neuroinflammation
Table 4.1 Components of microglial activation cascade
Chapter 6: The effects of hypoxia, hyperoxia, and oxygen fluctuations on oxidative signaling in the preterm infant and on retinopathy of prematurity
Table 6.1 Circulations of adult and developing eye
Table 6.2 Parameters used to classify retinopathy of prematurity
Table 6.3 Major animal models of OIR
Chapter 7: Oxidative damage in the retina
Table 7.1 Mapped and identified retinal dystrophy genes.
8
Chapter 9: Disorders of children
Table 9.1 Pediatric diseases possibly associated with enhanced oxidative stress
Table 9.2 Increased cerebrospinal fluid levels of oxidative stress biomarkers in acute encephalopathy.
38
Chapter 10: Oxidative stress in oral cavity: interplay between reactive oxygen species and antioxidants in health, inflammation, and cancer
Table 10.1 Reactive oxygen species and their main characteristics
Table 10.2 Exogenous antioxidants with particular significance to oral cavity conditions
Chapter 15: Role of oxidants and antioxidants in male reproduction
Table 15.1 Common oxygen-free radicals in male reproduction
Table 15.2 Common nitrogen-free radicals in male reproduction
Table 15.3 Overview of major methods of ROS and RNS detection
Table 15.4 Glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT).
6, 44, 52–57
Chapter 16: Role of oxidants and antioxidants in female reproduction
Table 16.1 Overview of the major methods of ROS and RNS detection
Table 16.2 Overview of oxidative stress and pregnancy complications
Chapter 24: Chemotherapy-mediated pain and peripheral neuropathy: impact of oxidative stress and inflammation
Table 24.1 Commonly used chemotherapy agents associated with peripheral neuropathy
Table 24.2 Taxanes and hypersensitivity reaction modulation
Table 24.3 Vitamin E and chemotherapy-induced peripheral neuropathy (CIPN)
Chapter 25: Grape polyphenol-rich products with antioxidant and anti-inflammatory properties
Table 25.1 Classification of phenolic compounds from grapes and wines
Table 25.2 Techniques proposed for the extraction of the phenolic fraction from grapes, grapes products, and by-products and the major variables affecting the process
Chapter 27: Superoxide dismutase mimics and other redox-active therapeutics
Table 27.1 Metal-centered reduction potential
E
1/2
versus NHE (for M
III
/M
II
redox couple, M being metal, except when indicated otherwise), for the catalysis of dismutation , log
k
red
(ONOO
−
) for the one-electron reduction of ONOO
−
to
•
NO
2
) and the lipophilicity of redox-active drugs expressed in terms of log value of the partition between
n
-octanol and water, log
P
OW
Chapter 30: Clinical trials and antioxidant outcomes
Table 30.1 Observational studies assessing clinical outcomes associated with the consumption of antioxidant vitamins
Table 30.2 Large interventional trials of antioxidant vitamins
Chapter 31: Statistical approaches to make decisions in clinical experiments
Table 31.1 The R commands that produce introductory descriptive statistics based on a numerical vector
x
Table 31.2 Comparison of the classical EL and density-based EL approaches
Oxidative Stress and Antioxidant Protection
The Science of Free Radical Biology and Disease
EDITED BY
Donald Armstrong
Robert D. Stratton
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved
Published by John Wiley & Sons, Inc., Hoboken, New Jersey
Published simultaneously in Canada
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Cover image: Getty/Luk Cox
List of contributors
Aneela Afzal
Advanced Imaging Research Center Oregon Health and Science University Portland, OR, USA
Mohammad Afzal
Department of Biological Sciences Faculty of Science Kuwait University Safat, Kuwait
Ashok Agarwal
American Center for Reproductive Medicine Cleveland Clinic Cleveland, OH 44195, USA
María José Alcaraz
Department of Pharmacology and IDM University of Valencia Valencia, Spain
Ryyan Alobaidi
Pathology Department King Saud University Riyadh, KSA
Juan A. Ardura
Bone and Mineral Metabolism Laboratory Instituto de Investigación Sanitaria (IIS) – Fundación Jiménez Díaz and UAM Madrid, Spain
Donald Armstrong
Department of Biotechnical and Clinical Laboratory SciencesState University of New York at Buffalo Buffalo, NY, USA
Department of Ophthalmology University of Florida College of Medicine Gainesville, FL, USA
Ines Batinic-Haberle
Department of Radiation Oncology Duke University School of Medicine Durham, NC, USA
Maurizio Battino
Department of Dentistry and Specialized Clinical Sciences Biochemistry Section Università Politecnica delle Marche Ancona, Italy
Bogdan Calenic
Department of Biochemistry Faculty of Dental Medicine University of Medicine and Pharmacy ‘CAROL DAVILA’ Bucharest, Romania
Jing Chen
Department of Pathology, Immunology, and Laboratory Medicine University of Florida College of Medicine Gainesville, FL, USA
Xiwei Chen
Department of Biostatistics School of Public Health and Health Professions State University of New York at Buffalo
Renan C. Chisté
Departamento de Ciências Químicas Faculdade de Farmácia Universidade do Porto REQUIMTE 4050-313 Porto, Portugal
Patrick Colahan
Department of Large Animal Clinical Sciences College of Veterinary Medicine University of Florida Gainesville, FL, USA
D. Scott Covington
Healogics, Inc. Jacksonville, FL, USA
Anna Dietrich-Muszalska
Department of Biological Psychiatry The Chair of Experimental and Clinical Physiology Medical University of Lodz Lodz, Poland
Herminia Domínguez
Departamento de Enxeñería Química Facultad de Ciencias Universidade de Vigo (Campus Ourense) Ourense, Spain
Hassan A. N. El-Fawal
The Pharmaceutical Research Institute and Neurotoxicology Laboratory Albany College of Pharmacy and Health Sciences Albany, NY, USA
Pedro Esbrit
Bone and Mineral Metabolism Laboratory Instituto de Investigación Sanitaria (IIS) – Fundación Jiménez Díaz and UAM Madrid, Spain
Elena Falqué
Departamento de Química Analítica Facultad de Ciencias Universidade de Vigo (Campus Ourense) Ourense, Spain
Eduarda Fernandes
Departamento de Ciências Químicas Faculdade de Farmácia Universidade do Porto REQUIMTE 4050-313 Porto, Portugal
Marisa Freitas
Departamento de Ciências Químicas, Faculdade de Farmácia Universidade do Porto REQUIMTE 4050-313 Porto, Portugal
Natan Gadoth
