Oxidative Injury in Dermatopathology

369 Pages·1992·6.45 MB·English

by  Dr. phil. nat., Dr. med. Jürgen Fuchs (auth.)

Jt irgen Fuchs
Oxidative Injury
in Dermatopathology
With 122 Figures and 17 Tables
Springer -Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
Dr. phil. nat., Dr. med. Jiirgen Fuchs
Klinikum der Johann Wolfgang Goethe-UniversiHit
Zentrum der Dermatologie und Venerologie
Abteilung II
Theodor-Stern-Kai 7
W-6000 Frankfurt 70, FRG
ISBN-13:978-3-642-76825-5 e-ISBN-13:978-3-642-76823-1
DOl: 10.1007/978-3-642-76823-1
Library of Congress Cataloging·in-Publication Data
Fuchs, J. (Jiirgen), 1957 - Oxidative injury in dennatopathology / J.Fuchs. p. cm. Inclu
des bibliographical references and index.
ISBN-13 :978-3-642-76825-5
1. Skin - Pathophysiology. 2. Active oxygen -Pathophysiology. 3. Free radicals (Chemistry)
-Pathophysiology. I. Title. [DNLM: 1. Oxygen - adverse effects. 2. Oxygen - metabolism.
3. Skin Diseases. WR 140 F9510j RL96.F83 1992 616.5'07 - dc20 DNLMlDLC 91-5192
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Preface
Dermatology is a complex and puzzling world of itching bumps, pim
ples, and rashes. The multitude of clinically distinct skin diseases,
their frequently unresolved pathogenesis, and the exponentially in
creasing amount of scientific information add to the confusion about
skin diseases. The great prevalence of skin diseases makes them an
urgent priority for intensive research effort, and although many
scientists and academic clinicians are vigorously trying to uncover
their secrets, we are only at the very brink of understanding the etiol
ogy of most dermatoses.
The principle mechanisms of general organ pathology (physical,
chemical, microbial, ischemic, degenerative, and neoplastic disturb
ances) are believed to be relatively well understood. In contrast to
skin pathomorphology, however little is known regarding the bio
chemistry and physiology of dermatoses. The difficulty in under
standing skin diseases may be overcome partially by finding biome
dical simplifications, and the concept of "oxidative injury in
dermatopathology" is just such a simplification. It should, of course,
always be kept in mind that no single mechanism alone can explain
the pathogenesis of a disease and that there may be a danger of over
looking other important biological determinants.
One major mechanism involved in organ pathology is oxygen me
tabolism and the formation of reactive oxygen species, such as the
superoxide anion and hydroxyl radical. The continuous exposure of
aerobic organisms to oxygen leads to tissue destruction when the flux
of reactive oxygen species is high, or when protective antioxidant
mechanisms fail: Humans do not usually become rancid while they
are alive, even when they consume increased amounts of oxygen,
such as occurs during strenuous physical exercise, as their polyunsa
turated fatty acids are well protected by efficient antioxidant mecha
nisms. However, these antioxidant defenses break down after death,
and the human body takes up much more oxygen within the first
3 days post mortem than during the same time period when alive and
breathing.
In the past decade, increasing attention has been paid to the role
of reactive oxygen species and free radicals in dermatopathology,
although there is still controversy over how and to what extent free
VI Preface
radicals and reactive oxygen species participate in organ pathology,
particularly in skin. This skepticism reflects both our inability to
measure and analyze exactly biochemical reactions in skin induced
by reactive oxygen species, and some scientific ignorance regarding
what is occurring in skin at a biochemical level.
Despite intensive and worldwide research efforts on oxidative
skin injury, a comprehensive analysis of the existing experimental
and clinical data is not available. This work is the result of my efforts
to produce a state-of-the-art review of the topic of oxidative injury in
dermatopathology, with objective of summarizing and discussing,
from the perspective of an academic clinician, developments in our
understanding of the role of free radicals and reactive oxygen spe
cies.
Most of the opinions and hypotheses presented in this book were
extracted from the references cited, and a few results and statements
were literally translated from the biomedical literature, including my
own studies. The review of the literature carried out reveals that pub
lications sometimes contain differences in results, and that con
troversy exists about interpretation of other results. Occasionally,
authors make speculations based on a limited amount of solid and
direct experimental evidence.
This book should serve as a valuable source of information for
dermatologists and biomedical scientists interested in the field of
free radicals and reactive oxygen species in cutaneous biology and
medicine. A comprehensive list of references is also provided to en
able the interested reader to obtain more detailed background infor
mation. I am aware that the physiological limitations of the human
mind only enable me as an individual to give a subjective perspective
on this topic, and hope that this does not detract from the value of
the work.
Ju rgen Fuchs
Contents
Chapter 1 History of a Concept . . . . . . . . . . . . . .. 1
Chapter 2 The Skin and Oxidative Stress 5
A. Introduction .............. . 5
I. Skin and Environmental Stress 5
II. Oxidative Stress . . . . . . . . . . . . . . . . . . . . 6
III. Skin as a Target Organ of Oxidative Injury .... 6
B. Biological Oxidants ..................... . 7
I. Superoxide Anion Radical ............. 11
II. Hydrogen Peroxide . . . . . . . . . . . . . . . . .. 12
III. Hydroxyl Radical . . . . . . . . . . . . . . . . . .. 13
IV. Singlet Oxygen .................... 14
V. Transition Metals . . . . . . . . . . . . . . . . . .. 15
VI. Radical Chelates ................... 17
VII. Hydroperoxides and Lipid Radicals ........ 17
VIII. Thiyl Radicals . . . . . . . . . . . . . . . . . . . .. 21
c.
Production Sites of Reactive Oxidants in Skin ....... 22
I. Plasma Membrane ................. . 24
II. Mitochondria ......... . . . . . . . . . . . . 25
III. Microsomes 28
IV. Peroxisomes 29
V. Cytosol ... 30
D. Targets of Reactive Oxidants in Skin ............ 30
I. Lipids ......................... 31
1. Skin Lipid Composition . . . . . . . . . . . . .. 32
2. Lipid Peroxidation in Skin ............ 33
VIII Contents
II. Proteins ............ . 35
1. Collagen . . . . . . . . . . . . 36
2. Proteases and Antiproteases 39
3. Amyloid .......... . 41
4. Amino Acid Racemization 42
III. Carbohydrates 43
IV. Nucleic Acids ....... . 44
E. The Antioxidant System of the Skin 48
I. Superoxide Dismutase 50
II. Catalase .......... . 52
III. Peroxidases ................ . 53
IV. The Enzymic Glutathione System . 54
V. Thioredoxin Reductase System . 56
VI. Lipoamide System ........ . 57
VII. NADPH Ubiquinone Reductase . 60
VIII. Nonenzymic Protein Antioxidants 60
IX. Hydrophilic Antioxidants 61
1. Thiols .. 61
2. Ascorbate . . . . . . . 65
3. Urate 68
X. Lipophilic Antioxidants 69
1. Tocopherol ..... . 69
2. Vitamin A and Carotenoids 74
3. Ubiquinols/Ubiquinones 77
4. Bilirubin . . . . . . . . . . . 78
XI. Antioxidant Capacity of Skin . . . . . . . 78
1. Regulation of the Skin Antioxidant Potential 79
F. Biological Models for Studying Oxygen Toxicity 82
I. Exercise Training . . . . . . . . 82
II. Hyperbaric Oxygen Treatment ..... 83
Chapter 3 Reactive Oxidants and Antioxidants
in Skin Pathophysiology . . . . . . . . . . . . . . . . 87
A. Electromagnetic Radiation ....... . 87
I. Ionizing Radiation ....... . 87
1. Formation of Reactive Species 87
2. Skin Damage ................... . 88
Contents IX
3. Ionizing Radiation and Lipid Peroxidation 89
4. Oxygen as a Radiation Sensitizer 89
5. Skin Radioprotection by Antioxidants 90
II. Nonionizing Radiation . . . . . . . 91
1. Formation of Reactive Oxidants
by Ultraviolet Light ....... 91
2. Ultraviolet-Light-Induced Skin Damage 92
3. Photoprotection by Antioxidants 96
4. Ultraviolet Light Effects on Skin Antioxidants 99
5. Infrared Radiation 102
6. Ultrasound .......... 102
III. Photosensitization ....... 103
1. Endogenous Photosensitizers 104
2. Exogenous Photos ensitizers 112
IV. Photoaging ........... 119
V. Photo carcinogenesis ...... 120
1. Photocarcinogenesis and Lipid Peroxidation 122
2. Photocarcinogenesis and Antioxidants ... 123
VI. Photoimmunology ................ 124
VII. Skin Diseases with Abnormal Reactions to Light 125
1. Lupus Erythematosus . . . . . . . . . . . . .. 126
2. Diseases with Increased Cellular Susceptibility 127
B. Mechanical and Thermal Skin Trauma 129
I. Wound Healing 129
II. Skin Burns 131
C. Skin Ischemia . . . 133
I. Acute Skin Response to Ischemia 134
II. Hematoma and Venous Ulcers .. 137
III. Skin Ischemia After Burn/Frostbite 137
D. Microbial Skin Diseases 138
I. Autotoxicity 138
E. Skin Aging ... 143
I. Collagen 144
II. Elastin . 145
III. Glycosaminoglycans 145
IV. Lipid Peroxidation .. 145
V. Fluorescent Pigments 146
VI. Amyloid . . . 147
VII. Antioxidants ..... 147
X Contents
F. Skin Immunology ........................ 148
G. Skin Inflammation ....................... 150
I. Phagocytes . . . . . . . . . . . . . . . . . . . . . .. 150
1. Neutrophil Granulocytes ............. 151
2. Eosinophil Granulocytes ............. 154
3. Macrophages .................... 155
4. Reactive Oxidants and Protease Inhibitors ... 156
II. Immune Complexes and Endothelial Injury . . . . 157
III. Clastogenic Products ................. 158
IV. Lipid Peroxidation Products . . . . . . . . . . . . . 159
V. Prostanoid Metabolism . . . . . . . . . . . . . . .. 162
VI. Reactive Oxidants as Modulators of Inflammation 164
H. Oxidative Injury in Skin Diseases .............. 165
I. Skin Diseases with Vasculitis ........... . 166
1. Neutrophilic Vasculitis ............. . 167
2. Lymphocytic Vasculitis ............. . 168
II. Mesenchymal Autoimmune Disorders . . . . . . . 168
1. Systemic Lupus Erythematosus . . . . . . . . . . 169
2. Progressive Systemic Sclerosis ......... . 171
III. Skin Diseases with Tissue Neutrophilia ..... . 173
1. Psoriasis Vulgaris . . . . . . . . . . . . . . . . . . 173
2. Sweet's Syndrome ................ . 176
3. Dermatitis Herpetiformis Duhring . . . . . . . . 177
IV. Skin Diseases with Tissue Eosinophilia ...... . 178
1. Bullous Pemphigoid ............... . 178
2. Pemphigus Herpetiformis . . . . . . . . . . . . . 178
V. Skin Diseases with Tissue Lymphocytosis .... . 179
1. Atopic Dermatitis ................ . 179
VI. Skin Diseases with Deficiency
in Nutritional Antioxidants ............ . 180
1. Kwashiorkor Dermatitis 180
I. Skin Carcinogenesis ...................... 180
I. Reactive Oxidants in Carcinogenesis . . . . . . .. 182
II. Reactive Oxygen Species in Tumor Promotion .. 182
III. Peroxides as Tumor Promotors ........... 184
IV. Phorbol Ester Type Tumor Promotors . . . . . .. 185
V. Modulation of Pro-and Antioxidant Skin Enzymes
by Tumor Promotors . . . . . . . . . . . . . . . . . 186
VI. Antioxidants as Antipromotors and Antiinitiators 187
VII. Endogenous Antioxidants in Skin Neoplasms . .. 189
Contents XI
Chapter 4 Dermatopharmacology 191
A. Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . .. 191
I. Tocopherol ...................... 191
II. Superoxide Dismutase . . . . . . . . . . . . . . .. 198
III. Retinoids ....................... 199
IV. Carotenoids . . . . . . . . . . . . . . . . . . . . .. 201
V. Anthralin ....................... 202
VI. Organic Gold Compounds . . . . . . . . . . . . .. 208
VII. Glucocorticosteroids
and Nonsteroidal Antiphlogistic Drugs ...... 210
VIII. Tetracyclines ................. 211
IX. Metronidazole ................ 212
X. Colchicine . . . . . . . . . . . . . . . . . . . 213
XI. Dapsone . . . . . . . . . . . . . . . . . . . . 214
XII. Clofazimine . . . . . . . . . . . . . . . . . . . . .. 216
XIII. Thalidomide . . . . . . . . . . . . . . . . . . . . .. 217
XIV. Iodide ......................... 218
XV. Chloroquine . . . . . . . . . . . . . . . . . . . . .. 219
XVI. Flavonoids . . . . . . . . . . . . . . . . . . . . . .. 219
XVII. Zinc .......................... 222
XVIII. Benzoyl Peroxide . . . . . . . . . . . . . . . . . .. 223
XIX. Tetrachlorodecaoxide ................ 224
XX. Dimethylsulfoxide .................. 225
XXI. Hyperbaric Oxygen ................. 225
B. Photochemotherapy . . . . 225
I. 8-Methoxypsoralen . . . . . . . . . . . . . . . .. 226
II. Hematoporphyrin .................. 230
III. Goeckermann Therapy ..... . . . .. 231
IV. Ingram Therapy. . . . . . . . . . . . . . . . . . .. 232
Chapter 5 Dermatotoxicology 233
A. Irritant Contact Dermatitis and Skin Necrosis ....... 234
I. Lipid Peroxidation Products . . . . . . . . . . . .. 234
II. Anticancer Agents .................. 235
III. Charge Transfer Mechanism ............ 236
IV. Chemical Warfare Agents . . . . . . . . . . . . .. 237