Antioxidants in Bio. and Med. - Essens., Advances, Clin. Applns. - Y. Li (Nova, 2011) WW

431 Pages·2011·5.83 MB·English

ANTIOXIDANTS IN BIOLOGY AND
MEDICINE: ESSENTIALS, ADVANCES,

AND CLINICAL APPLICATIONS

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ANTIOXIDANTS IN BIOLOGY AND
MEDICINE: ESSENTIALS, ADVANCES,

AND CLINICAL APPLICATIONS

YUNBO LI

Nova Science Publishers, Inc.
New York

Copyright © 2011 by Nova Science Publishers, Inc.

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Library of Congress Cataloging-in-Publication Data
Antioxidants in biology and medicine: essentials, advances, and clinical
applications / author, Yunbo Li.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-61209-466-3 (eBook)
1. Antioxidants. 2. Active oxygen. I. Li, Yunbo.
[DNLM: 1. Antioxidants. QV 325]
QP535.O1A585 2010
616.07'1--dc22
2010041342

Published by Nova Science Publishers, Inc. † New York

Contents

Preface

vii

SECTION I
INTRODUCTION TO OXIDATIVE STRESS AND ANTIOXIDANTS
1

Chapter 1
Introduction to Oxidative Stress

3

Chapter 2
Introduction to Antioxidants

21

SECTION II
ANTIOXIDANTS SYNTHESIZED BY CELLS

31

Chapter 3
Superoxide Dismutase

33

Chapter 4
Catalase

47

Chapter 5
Glutathione and its Synthesizing Enzymes

59

Chapter 6
Glutathione Peroxidase

73

Chapter 7
Glutathione Reductase

85

Chapter 8
Glutathione S-Transferase

91

Chapter 9
Glutaredoxin

103

Chapter 10
Thioredoxin

111

Chapter 11
Peroxiredoxin

123

Chapter 12
Thioredoxin Reductase

135

Chapter 13
Sulfiredoxin

143

Chapter 14
Methionine Sulfoxide Reductase

149

Chapter 15
Heme Oxygenase

159

Chapter 16
NAD(P)H:Quinone Oxidoreductase

179

Chapter 17
Paraoxonase

197

Chapter 18
Metal Ion Sequestering Proteins

217

Chapter 19
Other Non-Protein Antioxidants Synthesized by Cells

239

Contents
vi

SECTION III
ANTIOXIDANTS DERIVED FROM THE DIET

263

Chapter 20
Vitamin C

265

Chapter 21
Vitamin E

281

Chapter 22
Carotenoids

297

Chapter 23
Phenolic Compounds

315

SECTION IV
SYNTHETIC ANTIOXIDANTS

337

Chapter 24
Antioxidant Enzyme Mimetics

339

Chapter 25
Glutathione Precursors

353

Chapter 26
Spin Traps

367

Chapter 27
Nanomaterials

377

Index

389

Preface

Molecular oxygen is essential for aerobic life, yet incomplete reduction or excitation of
molecular oxygen during aerobic metabolisms results in the inevitable formation of reactive
oxygen species (ROS). ROS are capable of causing damage to cellular constituents, including
proteins, lipids, and nucleic acids. As such, aerobic organisms, including mammals have
evolved a series of complementary antioxidant enzymes and non-enzymatic antioxidant mo-
lecules to control ROS and thereby protect critical biomolecules from oxidative damage. In
addition, many diet-derived compounds have antioxidant activities and thus also contribute to
the mammalian antioxidant defenses. Under physiological conditions, ROS and antioxidant
defenses are generally in balance. However, increased formation of ROS or compromised
antioxidant defenses may disrupt this balance, leading to oxidative stress that may eventually
contribute to the development of many diseases.
The last two to three decades have witnessed the remarkable advances in our knowledge
about ROS and antioxidants in biology and medicine. It has been increasingly recognized that
ROS play an important role in diverse disease processes, including cardiovascular disorders,
diabetes, neurodegeneration, and cancer. In line with this notion, accumulating evidence also
demonstrates the effectiveness of antioxidant-based strategies for the intervention of an in-
creasing number of disease processes that involve an oxidative stress mechanism. In this con-
text, many synthetic antioxidant compounds have been developed, which can also be used to
augment antioxidant defenses to protect against oxidative stress-associated disease pathophy-
siology. New knowledge in antioxidant biology and medicine will certainly further enhance
our ability to develop more effective mechanistically-based strategies to combat human dis-
eases that involve an oxidative stress component.
This book covers both the fundamentals and the most recent advances in antioxidant re-
search in biology and medicine. The aim of the book is to provide a critical evaluation of the
various endogenous and exogenous antioxidants with an emphasis on their role in health and
disease. To this end, the book focuses on discussing solid scientific evidence obtained from
basic research in mammalian models of human diseases as well as studies conducted directly
in human subjects. The book is divided into four sections, as listed below.

Section I: Introduction to Oxidative Stress and Antioxidants

Section II: Antioxidants Synthesized by Cells

Section III: Antioxidants Derived from the Diet

Section IV: Synthetic Antioxidants

Preface
viii

To set a stage for the subsequent discussion on how individual antioxidants function to
protect against oxidative stress and disease processes, Section I introduces the basic know-
ledge on ROS and oxidative stress. It also provides an overview of the different kinds of anti-
oxidants, the molecular regulation of antioxidant genes, and the antioxidant-based strategies
for disease intervention. Section I has two chapters.
Section II consists of seventeen chapters devoted to the discussion of each of the major
endogenous antioxidants synthesized by cells with respect to their basic biology and in-
volvement in health and disease. Each chapter covers knowledge in three major areas: (1)
basic biochemistry and molecular regulation, (2) animal studies on the role in disease
processes, and (3) human studies and clinical applications.
Section III contains four chapters that cover the major antioxidants derived from the diet:
vitamin C, vitamin E, carotenoids, and phenolic compounds. The biochemical properties and
role in health and disease (including both experimental and clinical evidence) for each of
these diet-derived antioxidants are discussed.
Section IV consists of four chapters on synthetic antioxidants, including antioxidant en-
zyme mimetics, glutathione precursors, spin traps, and nanomaterials. These chapters describe
the chemical and biochemical properties of each of the above four classes of synthetic anti-
oxidants with an emphasis on their protective effects in disease processes in both experimen-
tal animals and human subjects.
It is hoped that this book by integrating knowledge on antioxidants from essentials to ad-
vances, and from basic research to clinical applications will provide the reader a unique ap-
proach to understanding the rapidly evolving field of antioxidants in biology and medicine.

Yunbo Li, MD, PhD
Blacksburg, Virginia
January, 2011

SECTION I

INTRODUCTION TO OXIDATIVE STRESS

AND ANTIOXIDANTS

Utilization of molecular oxygen by aerobic organisms, including mammals leads to the
inevitable formation of reactive oxygen and nitrogen species (ROS/RNS) from various meta-
bolic processes. ROS/RNS have the potential to damage cellular constituents. As such, aero-
bic organisms have evolved a number of antioxidants to protect critical biomolecules from
ROS/RNS-mediated damage. Under physiological conditions, formation of ROS/RNS and
functioning of antioxidants are generally in balance. However, increased ROS/RNS produc-
tion or compromised antioxidant defenses may disrupt this balance, leading to potentially
detrimental conditions, such as oxidative stress injury. Understanding of the basic biology of
ROS/RNS and oxidative stress is crucial for developing antioxidant-based strategies for the
intervention of diseases involving an ROS/RNS-dependent mechanism. Section I introduces
the basics related to ROS/RNS and oxidative stress, and provides an overview of antioxidants
and their gene regulation. This sets a stage for the subsequent chapters devoted to the discus-
sion of individual antioxidants in biology and medicine. Section I consists of two chapters.