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Biomarkers for Antioxidant Defense and Oxidative Damage: Principles and Practical Applications Biomarkers for Antioxidant Defense and Oxidative Damage: Principles and Practical Applications Edited By Giancarlo Aldini Kyung-Jin Yeum Etsuo Niki Robert M. Russell A John Wiley & Sons, Inc., Publication Edition f rst published 2010 © 2010 Blackwell Publishing Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientif c, Technical, and Medical business to form Wiley-Blackwell. Editorial Off ce 2121 State Avenue, Ames, Iowa 50014-8300, USA For details of our global editorial off ces, for customer services, and for information about how to apply for permission to reuse the copyright material in this book, please see our Website at www.wiley.com/wiley-blackwell. Authorization to photocopy items for internal or personal use, or the internal or personal use of specif c clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee code for users of the Transactional Reporting Service is ISBN-13: 978-0-8138-1535-0/2010. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, ser vice marks, trademarks, or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Library of Congress Cataloging-in-Publication Data Biomarkers for antioxidant defense and oxidative damage : principles and practical applications / edited by Giancarlo Aldini . . . [eatl .]. p. ; cm. Includes bibliographical references and index. ISBN 978-0-8138-1535-0 (hardback : alk. paper) 1. Antioxidants. 2. Oxidative stress. 3. Active oxygen. 4. Biochemical markers. I. Aldini, Giancarlo. [DNLM: 1. Biological Markers. 2. Antioxidants–physiology. 3. Oxidative Stress–physiology. QW 541 B6159 2010] RB170.B566 2010 613.2 ′86–dc22 2010011386 ISBN 9780813815350 A catalog record for this book is available from the U.S. Library of Congress. Set in 9.5 on 11 pt Times New Roman by Toppan Best-set Premedia Limited Printed in Singapore Disclaimer The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specif cally disclaim all warranties, including without limitation warranties of f tness for a particular purpose. No warranty may be created or extended by sales or promotional materials. The advice and strategies contained herein may not be suitable for every situation. This work is sold with the understanding that the pub lisher is not engaged in rendering legal, accounting, or other professional services. If professional assistance is required, the services of a competent professional person should be sought. Neither the pub lisher nor the author shall be liable for damages arising herefrom. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of fur ther information does not mean that the author or the pub lisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. 1 2010 Contents Preface vii Contributors ix 1. Antioxidant Activity and Oxidative Stress: An Overview 3 Kyung-Jin Yeum, Robert M. Russell, and Giancarlo Aldini 2. Enzymatic Antioxidant Defenses 21 Sayuri Miyamoto, Hirofumi Arai, and Junji Terao 3. Antioxidants as Biomarkers of Oxidative Stress 35 Ikuyo Ichi and Shosuke Kojo 4. LDL Oxidation as a Biomarker of Antioxidant Status 51 Mohsen Meydani, EunHee Kong, and Ashley Knight 5. The Isoprostanes: Accurate Markers and Potent Mediators of Oxidant Injury in Vivo 65 Joshua D. Brooks, Brian E. Cox, Klarissa D. Hardy, Stephanie C. Sanchez, Sonia Tourino, Tyler H. Koestner, Jocelyn R. Hyman-Howard, and Ginger L. Milne 6. Hydroxyoctadecadienoic Acid (HODE) as a Marker of Linoleic Acid Oxidation 85 Yasukazu Yoshida and Etsuo Niki 7. Oxysterols: Potential Biomarkers of Oxidative Stress 99 Luigi Iuliano and Ulf Diczfalusy 8. Lipid Peroxidation Originating α,β-unsaturated Aldehydes and Their Metabolites as Biomarkers 117 Françoise Guéraud v vi Contents 9. Oxidative Modif cation of Proteins: An Overview 137 Paul J. Thornalley and Naila Rabbani 10. Immunochemical Detection of Lipid Peroxidation-specif c Epitopes 157 Koji Uchida 11. Mass Spectrometric Strategies for Identif cation and Characterization of Carbonylated Peptides and Proteins 173 Marina Carini and Marica Orioli 12. Nitrotyrosine: Quantitative Analysis, Mapping in Proteins, and Biological Signif cance 199 José M. Souza, Silvina Bartesaghi, Gonzalo Peluffo, and Rafael Radi 13. Ubiquitin Conjugates: A Sensitive Marker of Oxidative Stress 219 Fu Shang and Allen Taylor 14. Covalent Modif cations of Albumin Cys34 as a Biomarker of Mild Oxidative Stress 229 Giancarlo Aldini, Kyung-Jin Yeum, and Giulio Vistoli 15. Protein S-glutathionylation and S-cysteinylation 243 Graziano Colombo, Aldo Milzani, Roberto Colombo, and Isabella Dalle-Donne 16. DNA Oxidation, Antioxidant Effects, and DNA Repair Measured with the Comet Assay 261 Mária Dušinská and Andrew R. Collins 17. Hydroxylated Nucleotides: Measurement and Utility as Biomarkers for DNA Damage, Oxidative Stress, and Antioxidant Eff cacy 283 Phyllis E. Bowen 18. Exocyclic DNA Adducts as Biomarkers of Antioxidant Defense and Oxidative Stress 319 Roger W.L. Godschalk Index 333 Preface Oxidative damage is known to be associated with the aging process and v arious chronic dis- eases such as atherosclerosis, diabetes, cataract, macular degeneration, and Alzheimer ’ s disease. Oxidative damage may be either a cause or an effect; therefore, its accurate measurement using sensitive and specif c biomarker is greatly needed by the scientif c community. When oxidative damage acts as a causati ve factor of disease, its biomark ers can be a useful tool to better understand the pathogenic mechanisms involved, f nd novel drug targets, and evaluate effective defense strategies such as phar maceuticals, nutraceuticals, or food and deri vatives. When oxidative stress is the disease ’ s effect, its measurement could pro vide early prediction of the onset and pro gression for the disease. Hence, o xidative stress biomark ers can be used for diagnosis, prognosis, and treatment eff cacy. Although signif cant methodological advances have been made since the de velopment of thiobarbituric acid reactive substances (TBARS) and total carbonyl assays, which were widely used in 1980s and 1990s for measuring oxidative damage, the achievement of a gold standard method to determine antioxidant defense/oxidative damage status is not yet at hand. The devel- opment and application of v arious biomarkers for measuring antio xidant defense/oxidative damage is an evolving research area. Biomarkers of oxidative damage can be classif ed as either direct or indirect methods. Direct methods measure the oxidation products involving substrates such as lipids, proteins, and nucleic acids. Indirect methods measure antio xidant status b y analyzing endogenous levels of enzymatic and nonenzymatic antioxidants, as well as the resis- tance of a biological matrix to an induced oxidative stress. This book describes the methodolo gical principles of cur rent state - of - the - art methods for measuring antioxidant activity/oxidative stress and their practical applications. In par ticular, the f rst three chapters describe conventional biomarkers as well as recent advances for measur- ing antioxidants and antioxidant capacity. Basic concepts and methodolo gies of widely used assays and their applications are critically evaluated. In addition, factors affecting antioxidant capacity in a biological system as well as the biological relevance of hydrophilic and lipophilic capacity assays are discussed. Determination of o xidative damage using lipid pero xidation products and metabolites is covered in chapters 4 through 7 . In par ticular the follo wing specif c biomarkers for lipid peroxidation are considered: isoprostanes (arachidonic acid C20:4 o xidation products), vii viii Pref ace hydroxyloctadecaenoic acid (linoleic acid C18:2 o xidation products), oxysterols (cholesterol oxidation products), and reactive carbonyl species from lipid peroxidation. Chapters 9 through 11 cover an outstanding area in biomarker discovery, that of protein oxidation. After an intro- duction on oxidative modif cations of proteins, recent advances in the measurement of carbon- yls adducted proteins by antibodies and mass spectrometr y are discussed. These chapters are followed by discussions of the recent de velopment on protein tyrosine nitration (Chapter 12 ) and ubiquitin -c onjugates (Chapter 13) to deter mine mild and se vere oxidative damage. Biomarkers that have recently been developed thanks to cutting - edge technology, which deter- mines oxidative modif cations of protein thiols, are presented in chapters 14 and 15 . Well recognized biomarkers as well as recently developed biomarkers for DNA oxidative damage and their application in humans are discussed in chapters 16 through 18 . In particular, methodological aspects for the measurement of DN A oxidation (comet assay, hydroxylated nucleotides, and exocyclic DNA adducts) are described, together with their implication in rela- tion to chronic diseases. We believe that the cur rent book will be of a g reat interest to scientists w ho are involved in basic research on o xidation, applied scientists e valuating the effects of nutraceuticals or pharmaceutical compounds on antioxidant activity/oxidative status, and physicians who want to understand the degree of oxidative damage in patients with specif c chronic diseases.

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Biomarkers for Antioxidant Defense and Oxidative Damage: Principles and Practical Applications critically evaluates the basic concepts and methodologies of conventional biomarkers as well as current state-of-the-art assays for measuring antioxidant activity/oxidative stress and their practical appli
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