Nutritional Antioxidant Therapies: Treatments and Perspectives

Kaïs Hussain Al-Gubory • Ismail LaherEditors

Nutritional Antioxidant Therapies: Treatments and Perspectives

ISBN 978-3-319-67623-4 ISBN 978-3-319-67625-8 (eBook)https://doi.org/10.1007/978-3-319-67625-8

Library of Congress Control Number: 2018930884

© Springer International Publishing AG 2017This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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EditorsKaïs Hussain Al-GuboryNational Institute for Agricultural ResearchJouy-en-JosasFrance

Ismail LaherDepartment of Pharmacology and Therapeut Faculty of MedicineUniversity of British ColombiaVancouver, British ColumbiaCanada

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Preface

Before the creation of any life forms on earth, gas molecules were ubiquitous in the atmosphere. Among these molecules, oxygen became a key chemical element for biological organisms to respire and to produce the necessary energy for various activities of life. Existing in an environment where oxygen can have untoward risks seems paradoxical, since we breathe oxygen not only to survive but also to endure the consequences of the production of free radical and non-radical molecules col-lectively referred to as reactive oxygen species (ROS). Because ROS are generated as natural by-products of aerobic respiration and metabolism to become ubiquitous molecules in all biological system, every aspect in the life of aerobic organisms is affected by this paradox. Mitochondria are a major source of ROS production within and out of the cell. Our bodies produce ROS as part of normal physiological func-tions such as intracellular signaling and mediating some immune responses.

However, we are also exposed to multitude of human-made chemicals, such as pesticides, heavy metals, endocrine disruptors, ambient air particulate matter, and industrial solvents. Added to this ROS is accumulation resulting from unhealthy lifestyle behaviors, mainly poor diet habits, physical inactivity, tobacco smoking, alcohol consumption, and drug abuse.

Overproduction of ROS induces oxidative stress, a state where increased genera-tion of ROS overwhelms antioxidant protection, leading to oxidative damage of cellular macromolecules, including proteins, lipids, and nucleic acids. The conse-quences of this chemical oxidative damage include loss of enzyme activity, cell membrane alterations and damage, DNA lesions, and mutagenesis. During the past three decades, oxidative stress has been linked to prenatal and postnatal develop-mental disorders; to adult noncommunicable diseases, including diabetes, cancer, and reproductive, gastrointestinal, hepatic, renal, pulmonary, cardiovascular, and neurological diseases; and to the aging process. There is also a possibility that the risks of several noncommunicable and oxidative stress chronic diseases may have prenatal origins. Antioxidant nutritional therapies could therefore be highly benefi-cial to embryonic and fetal development, neonatal growth and health, maintenance of good adult health, and potentially healthy aging.

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Epidemiological and clinical studies have linked undernutrition, malnutrition, and unhealthy lifestyle behaviors to multiple diseases and premature aging in asso-ciation with oxidative stress due to insufficient antioxidant protections and ROS detoxification. In addition, industrial and agricultural activities contribute to the release of large quantities of chemical pollutants in the environment and have already resulted in widespread soil and water contamination. Exposure to these pol-lutants is inevitable as it occurs through the consumption of contaminated food and water as well as by air inhalation. Therefore, the ability to feed properly and to have healthy lifestyle behaviors is the greatest concern of humans, since we rely on our ability to generate safe nutrients, high-quality products, and healthy plant-based diets while minimizing adverse environmental impacts on health. There is increas-ing interest in seeking health remedies, leading to the need by many to resort to plant-based therapies since dietary organic and inorganic substances have signifi-cant antioxidant levels. Plant antioxidants have increased in popularity as evidenced by the widespread adherence to traditional medicine and its use as an adjuvant in conventional health care.

The purpose of our book was to assemble a series of expert reviews on the thera-peutic potential of plant antioxidants as effective and reliable natural compounds to combat oxidative stress omnipresent during the life of organisms in utero, postnatal development, adulthood, and aging. This book provides an overview of the use of plant-based antioxidant therapies in health promotion and disease prevention and treatment.

Kaïs Hussain Al-Gubory Ismail Laher

Preface

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Acknowledgments

The editors identified the need of a comprehensive reference book focusing on cur-rent knowledge of the therapeutic potential of plant antioxidants as a guide to reviving guidelines and nutritional health-promoting recommendations. This col-lection of reviews also aims to increase awareness of healthy nutrition, dietary habits, and diets.

This book is a collection of 20 peer-reviewed chapters, each of which is written by international content experts and collectively covers complementary themes related to the role of nutritional antioxidant therapies in health promotion and disease prevention. Assembling a multiauthored specialized book is usually a major challenge for authors and the editors, but in this case it has been an enjoy-able and fulfilling experience largely due to the enthusiasm of the authors, review-ers, and publisher.

It is with immense pleasure to gratefully acknowledge and congratulate all the authors and reviewers who helped us to assemble this book. In addition, we warmly thank our colleagues at Springer-Nature for their keen interest and commitment to the publication of this new book.

Lastly, we would like to thank our mentors, colleagues, and family members for their continued support and guidance.

Kaïs Hussain Al-GuboryIsmail Laher

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1 Introducing Chapter: Phytochemicals, Antioxidant Therapy, Opportunities and Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Kaïs Hussain Al-Gubory

2 Plants of Indian Traditional Medicine with Antioxidant Activity . . . 27Abhishek Das, Dipankar Chaudhuri, Rhitajit Sarkar, Nikhil Baban Ghate, Sourav Panja, and Nripendranath Mandal

3 Antioxidant Potential of African Medicinal Plants . . . . . . . . . . . . . . . 65Ashwell Rungano Ndhlala, Bhekumthetho Ncube, Hafiz Ahmed Abdelgadir, Christian Phillipus Du Plooy, and Johannes Van Staden

4 Plant-Based Diets for Health Maintenance and Disease Prevention: Why and How? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89Kaïs Hussain Al-Gubory

5 Antioxidants in Reproductive Health and Fertility . . . . . . . . . . . . . . . 113Rachel L. Darché, Elizabeth H. Ruder, Jeffrey Blumberg, Terryl J. Hartman, and Marlene B. Goldman

6 Antioxidant Therapy in Assisted Reproductive Technologies. . . . . . . 137Ashok Agarwal and Damayanthi Durairajanayagam

7 Plant Antioxidants in the Prevention of Early Life Programming Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159Kaïs Hussain Al-Gubory

8 Antioxidants Against Environmental Factor- Induced Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189Jorge H. Limón Pacheco, Marta A. Carballo, and María E. Gonsebatt

Contents

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9 Antioxidant Therapy Against Persistent Organic Pollutants and Associated Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217Bernhard Hennig, Michael C. Petriello, Bradley J. Newsome, Jordan T. Perkins, and Dandan Liu

10 Antioxidants in Physical Exercise and Sports Performance . . . . . . . . 247Li Zuo, Tingyang Zhou, and Chia-Chen Chuang

11 Plant Polyphenols in Healthcare and Aging . . . . . . . . . . . . . . . . . . . . . 267Kanti Bhooshan Pandey and Syed Ibrahim Rizvi

12 Free Radicals and Antioxidants in Human Disease . . . . . . . . . . . . . . . 283Michael Lawson, Klaudia Jomova, Patrik Poprac, Kamil Kuča, Kamil Musílek, and Marian Valko

13 Protective Effects of Dietary Polyphenols in Human Diseases and Mechanisms of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307Tao Shen, Xiu-Zhen Han, Xiao-Ning Wang, Pei-Hong Fan, Dong-Mei Ren, and Hong-Xiang Lou

14 Plant Flavonoids in Health, Prevention, and Treatment of Chronic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347Aleksandra Kozłowska and Dorota Szostak-Węgierek

15 Dietary Polyphenols in the Prevention and Treatment of Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377Kanwal Rehman, Kaïs Hussain Al-Gubory, Ismail Laher, and Muhammad Sajid Hamid Akash

16 Targeting Complications of Diabetes with Antioxidants . . . . . . . . . . . 397Saeid Golbidi and Ismail Laher

17 Prevention of Type 2 Diabetes by Polyphenols of Fruits . . . . . . . . . . . 447H. P. Vasantha Rupasinghe, Nileeka Balasuriya, and Yanwen Wang

18 Antioxidants in the Prevention and Treatment of Liver Diseases . . . 467Sha Li, Ning Wang, Yi-Gang Feng, Hong-Yun Li, and Yibin Feng

19 Antioxidants in the Prevention and Treatment of Cancer . . . . . . . . . 493Jawad Alzeer, Rami Arafeh, and Kaïs Hussain Al-Gubory

20 Antioxidants in the Prevention and Treatment of Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523Sandeep Kumar Singh, Saripella Srikrishna, Rudy J. Castellani, and George Perry

Contents

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Contributors

Hafiz Ahmed Abdelgadir Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Scottsville, South Africa

Ashok  Agarwal Center for Reproductive Medicine, Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

Muhammad  Sajid  Hamid  Akash Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan

Kaïs Hussain Al-Gubory National Institute for Agricultural Research, Jouy-en-Josas, France

Jawad Alzeer Department of Chemistry, University of Zurich, Zurich, Switzerland

Rami Arafeh Biotechnology Research Center, Palestine Polytechnic University, Hebron, Palestine

Nileeka  Balasuriya Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada

Jeffrey Blumberg Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA

Marta Carballo Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Citogenética Humana y Genética Toxicológica (CIGETOX), Buenos Aires, Argentina

Rudy J. Castellani Department of Pathology, University of Maryland, Baltimore, MD, USA

Ruth Chan Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong, SAR, China

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Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China

Dipankar Chaudhuri Division of Molecular Medicine, Bose Institute, Kolkata, India

Chia-Chen  Chuang Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA

Rachel L. Darché Department of Obstetrics & Gynecology, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

Department of Community and Family Medicine, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

Abhishek Das Division of Molecular Medicine, Bose Institute, Kolkata, India

Damayanthi  Durairajanayagam Center for Reproductive Medicine, Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

Pei-Hong Fan Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China

Yi-Gang  Feng Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China

Yibin  Feng School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, People’s Republic of China

Nikhil  Baban  Ghate Division of Molecular Medicine, Bose Institute, Kolkata, India

Saeid  Golbidi Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

Marlene  B.  Goldman Department of Obstetrics & Gynecology, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

Department of Community and Family Medicine, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

María  E.  Gonsebatt Instituto de Investigaciones Biomédicas, Universidad Autónoma de México, Mexico city, Mexico

Xiu-Zhen Han Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China

Terryl J. Hartman Department of Epidemiology, Rollins School of Public Health & Winship Cancer Institute, Emory University, Atlanta, GA, USA

Contributors

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Bernhard Hennig Superfund Research Center, University of Kentucky, Lexington, KY, USA

Department of Animal and Food Sciences, College of Agriculture Food and Environment, University of Kentucky, Lexington, KY, USA

Klaudia  Jomova Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University, Nitra, Slovakia

Aleksandra Kozłowska Department of Social Medicine and Public Health, First Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland

Kamil Kuča Biomedical Research Center, University Hospital Hradec Kralove, University of Hradec Kralove, Hradec Kralove, Czech Republic

Ismail Laher Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

Michael  Lawson Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University, Nitra, Slovakia

Sha  Li School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, People’s Republic of China

Hong-Yun  Li Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China

Jorge  H.  Limón  Pacheco Instituto de Investigaciones Biomédicas, Universidad Autónoma de México, Mexico city, Mexico

Dandan Liu Superfund Research Center, University of Kentucky, Lexington, KY, USA

Department of Animal and Food Sciences, College of Agriculture Food and Environment, University of Kentucky, Lexington, KY, USA

Hong-Xiang Lou Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China

Nripendranath Mandal Division of Molecular Medicine, Bose Institute, Kolkata, India

Kamil Musílek Biomedical Research Center, University Hospital Hradec Kralove, University of Hradec Kralove, Hradec Kralove, Czech Republic

Bhekumthetho Ncube Agricultural Research Council, Vegetable and Ornamental Plant Institute (VOPI), Pretoria, South Africa

Ashwell Rungano Ndhlala Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Scottsville, South Africa

Bradley  J.  Newsome Superfund Research Center, University of Kentucky, Lexington, KY, USA

Contributors

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Department of Animal and Food Sciences, College of Agriculture Food and Environment, University of Kentucky, Lexington, KY, USA

Kanti Bhooshan Pandey Department of Biochemistry, University of Allahabad, Allahabad, India

Sourav Panja Division of Molecular Medicine, Bose Institute, Kolkata, India

Jordan T. Perkins Superfund Research Center, University of Kentucky, Lexington, KY, USA

Department of Animal and Food Sciences, College of Agriculture Food and Environment, University of Kentucky, Lexington, KY, USA

George Perry Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA

Michael  C.  Petriello Superfund Research Center, University of Kentucky, Lexington, KY, USA

Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY, USA

Christian Phillipus Du Plooy Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Scottsville, South Africa

Patrik Poprac Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia

Kanwal Rehman Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan

Dong-Mei Ren Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China

Syed  Ibrahim  Rizvi Department of Biochemistry, University of Allahabad, Allahabad, India

Elizabeth  H.  Ruder Department of Sports Medicine and Nutrition, School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, USA

H.P.  Vasantha  Rupasinghe Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada

Rhitajit Sarkar Division of Molecular Medicine, Bose Institute, Kolkata, India

Mandy Sea Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong, SAR, China

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China

Tao  Shen Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China

Contributors

xv

Sandeep Kumar Singh Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, UP, India

Saripella  Srikrishna Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, UP, India

Johannes Van Staden Agricultural Research Council, Vegetable and Ornamental Plant Institute (VOPI), Pretoria, South Africa

Dorota  Szostak-Węgierek Department of Human Nutrition, Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland

Cecilia  Tong Centre for Nutritional Studies, The Chinese University of Hong Kong, Hong Kong, SAR, China

Marian Valko Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia

Xiao-Ning Wang Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China

Ning Wang School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, People’s Republic of China

Yanwen  Wang Aquatic and Crop Resource Development, National Research Council of Canada, Charlottetown, PE, Canada

Jean Woo Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China

Suey Yeung Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China

Tingyang Zhou Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA

Li Zuo Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH, USA

Molecular Physiology and Rehabilitation Research Laboratory, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

Contributors

xvii

List of Abbreviations

AA Arachidonic acidABTS 2,2′-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acidACC Acetyl-coenzyme A carboxylaseACC CoA carboxylaseACE Angiotensin-converting enzymesAD Alzheimer’s diseaseADMA Asymmetric dimethylarginineADP Adenosine diphosphateAFB Aflatoxin BAFR Ascorbate free radicalAGE Advanced glycation end productsAhR Aryl hydrocarbon receptorAkt Protein kinase BALA Alpha-lipoic acidALD Alcoholic liver diseaseALS Amyotrophic lateral sclerosisALT Alanine transaminaseAMP Adenosine monophosphateAMPK 5′ Adenosine monophosphate-activated protein kinaseAngII Angiotensin IIAOPP Advanced oxidation protein productsAP-1 Activator protein-1aPKC Atypical protein kinase CAPOE ApolipoproteinAPP Amyloid precursor proteinAPX Ascorbate peroxidaseAQP AquaporinsAR Aldose reductaseARE Antioxidant response elementsARNT Aryl hydrocarbon receptor nuclear translocatorARs Androgen receptors

xviii

ART Assisted reproductive technologiesAs ArsenicAsc• − Ascorbate free radicalAsc2− Ascorbate radicalAscH− Ascorbate anionsAST Aspartate aminotransferaseATP Adenosine triphosphateAβ Amyloid betaAβ1-40 Amyloid β peptide-40BACE-1 Beta-site APP cleaving enzyme-1BAL British anti-LewisiteBCRP Breast cancer resistance proteinBDNF Brain-derived neurotrophic factorBe BerylliumBH4 Heme tetrahydrobiopterinBHA Butylated hydroxyanisoleBHT Butylated hydroxytolueneBP Blood pressureBPA Bisphenol ABUB1 Budding uninhibited by benzimidazoles 1C/EBPα CCAAT-enhancer-binding protein alphaC/EBPβ CCAAT-enhancer-binding protein βCARET Beta-carotene and retinol efficacy trialCAT CatalaseCBS Cystathionine b synthaseCCNB2 Cyclin B2Cd CadmiumCD Crohn’s diseaseCDC20 Cell-division cycle protein 20CDDP Cis-diammine dichloroplatinumCDKs Cyclin-dependent kinasesCDO Cysteine dioxygenaseCGs Catechin gallatesCHD Coronary heart diseaseCγL Cystathionine gamma lyaseCNS Central nervous systemCO Carbon monoxideCo CobaltCO2 Carbon dioxideCoQ10 Coenzyme Q10COX CyclooxygenaseCPP Central precocious pubertyCPT-1 Carnitine palmitoyltransferase-1Cr ChromiumCREB cAMP response element-binding protein

List of Abbreviations

xix

CSD Cysteine sulfinate decarboxylaseCSF Cerebrospinal fluidCu CopperCVDs Cardiovascular diseasesCy-3-glu Cyanidin-3-glucosideCYP Cytochromes P450CYP7A1 Cholesterol 7α-hydroxylaseCysDA 5-S-Vysteinyl-dopamined-ROMs Reactive oxygen metabolites testDAG DiacylglycerolDASH Dietary approaches to stop hypertensionDDAH Dimethylarginine dimethylamino hydrolaseDDE 2,2’-bis(4-Chlorophenyl)-1,1-dichloroethyleneDDT DichlorodiphenyltrichloroethaneDE Diesel exhaustDHAR Dehydroascorbate reductaseDHLA Dihydrolipoic acidDMB DemethyleneberberineDMES Diabetic Macular Edema StudyDMPS 2,3-Dimercapto-1-propanesulfonic acidDMSA Dimercaptosuccinic acid or succimerDMT1 Divalent metal transporter 1DNA Deoxyribonucleic acidDPP4 Dipeptidyl peptidase-4DPPH 2,2-Diphenyl-1-picrylhydrazylE2F5 Transcription factor E2F5EC EpicatechinECG Epicatechin gallateEDHF Endothelium-derived hyperpolarizing factorEDTA Ethylenediaminetetraacetic acidEGC EpigallocatechinEGCG Epigallocatechin gallateEGF Epidermal growth factoreNOS Endothelial nitric oxide synthaseERK Extracellular signal-regulated kinaseERK1/2 Extracellular signal-regulated protein kinases 1 and 2ERKs Extracellular signal-regulated protein kinasesERs Estrogen receptorsET-1 Endothelin-1F2-IsoPs F2-isoprostanesFAD Flavin adenine dinucleotideFAS Fatty acid synthaseFASTT Fast track and standard treatment trialFe IronFGFR2 Fibroblast growth factor receptor 2

List of Abbreviations

xx

FMN Flavin mononucleotideFOXO1 Forkhead box protein O1FRAP Ferric reducing antioxidant powerFRAP Fluorescence recovery after photobleachingFSH Follicle-stimulating hormoneFSH Follicle-stimulating hormoneFTC Ferric thiocyanateg-TE γ-TocotrienolG6Pase Glucose-6-phosphataseG6PD Glucose-6-phosphate dehydrogenaseGC Gas chromatographyGCL Glutamate cysteine ligaseGCS Glutamylcysteine synthetaseGHES Glucosyl hesperidinGLP-1 Glucagon-like peptide-1Glu Glucose transporterGLUT Glucose transporterGLUT4 Glucose transporter 4GNT GluconasturtiinGPAT-1 Glycerol-3-phosphate acyltransferase-1G6PD Glucose-6-phosphate dehydrogenaseGPR30 G-protein-coupled receptor 30GPX Glutathione peroxidaseGR Glutathione reductaseGS• Thiyl radicalsGSH GlutathioneGSS Glutathione synthetaseGSSG Glutathione disulfideGST M1 Glutathione S-transferase mu 1GST Glutathione S-transferaseGTC Green tea catechinsH2O2 Hydrogen peroxideHA Heterocyclic aminesHbA1c Hemoglobin A1cHbA1c Hemoglobin A1cHBV Hepatitis BHCC Hepatocellular carcinomaHCl Hydrochloric acidHCV Hepatitis C virusHcy HomocysteineHD Huntington’s diseaseHDL-C High-density lipoprotein cholesterol4-HNE 4-HydroxynonenalHES HesperidinHETEs Hydroxyeicosatetraenoic acids

List of Abbreviations

xxi

Hg MercuryHIF-1α Hypoxia-inducible factor 1αHLE-B3 Human lens epithelial cell lineHMG-CoA 3-Hydroxy-3-methylglutaryl-coenzyme AHNE 4-HydroxynonenalHO-1 Heme oxygenase-1HOCl Hypochlorous acidHOMA-IR Homeostatic model assessment of insulin resistanceHOPE Heart Outcomes Prevention EvaluationHpCDD 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxinHpETEs Hydroperoxyeicosatetraenoic acidshs-CRP High-sensitivity C-reactive proteinHSL Hormone-sensitive lipaseHSP Heat-shock proteinIBD Inflammatory bowel diseaseICAM-1 Intercellular adhesion molecule 1ICDH Isocitrate dehydrogenasesICSI Intracytoplasmic sperm injectionIDL Intermediate density lipoproteinIFN-γ Interferon gammaIFOAM International Federation of Organic Agriculture MovementsIHD Ischemic heart diseaseIKK IκB kinaseIL-1α Interleukin 1 alphaIL-1β Interleukin 1 betaIL-2 Interleukin 2IL-6 Interleukin 6IL-8 Interleukin 8iNOS Inducible nitric oxide synthaseIR Ionizing radiationIRS-1 Insulin receptor substrate 1IRS-2 Insulin receptor substrate 2ITCs IsothiocyanatesIUGR Intrauterine growth restrictionIVF In vitro fertilizationIVF/ET In vitro fertilization and embryo transferJNK c-Jun N-terminal kinaseKeap1 Kelch-like ECH-associated protein 1LDL-C Low-density lipoprotein cholesterolLDL Low-density lipoproteinLDLox Oxidized low-density lipoproteinLH Luteinizing hormoneLOO• Lipid peroxyl radicalsLOX LipoxygenaseLPH Lactase-phlorizin hydrolase

List of Abbreviations

xxii

LPS LipopolysaccharideLTB4 Leukotriene B4LTC4 Leukotriene C4LTs LeukotrienesMAG MonoglycerideMAPKs Mitogen-activated protein kinasesMCDD Methionine and choline-deficient dietMCI Mild cognitive impairmentMCP1 Monocyte chemoattractant protein-1MD Mediterranean dietMDA MalondialdehydeMEOS Microsomal ethanol oxidizing systemMMPs Matrix metalloproteinasesMPO MyeloperoxidaseMPP+ 1-Methyl-4-phenylpyridiniumMPT Mitochondrial permeability transitionMRL Maximum residue limitsMS Mass spectrometryMS Multiple sclerosisMTA Mitochondrial-targeted antioxidantmtDNA Mitochondrial DNAMTF-1 Metal-responsive transcription factor-1MYBL2 MYB proto-oncogene-like 2NAC N-Acetyl-cysteineNAD Nicotinamide adenine dinucleotideNADH Oxidized nicotinamide adenine dinucleotide phosphateNADPH Reduced nicotinamide adenine dinucleotide phosphateNAFLD Nonalcoholic fatty liver diseaseNASH Nonalcoholic steatohepatitisNCDs Noncommunicable diseasesNF-κB Nuclear factor-kappa BNHANES National Health and Nutrition Examination SurveyNi NickelNIH National Institutes of HealthNLCS Netherlands Cohort StudyNMR Nuclear magnetic resonanceNMU N-NitrosomethylureanNOS Neuronal nitric oxide synthaseNO• Nitric oxideNO2-Tyr 3-Nitro-tyrosineNO2 Nitrogen dioxideNOS Nitric oxide synthaseNQO1 Nicotinamide adenine dinucleotide phosphate:quinone oxidoreductaseNrf2 Nuclear factor (erythroid-derived 2)-like 2

List of Abbreviations

xxiii

O2 OxygenO3 Ozone1O2 Singlet oxygen•O2

− Superoxide radicalOAT OligoasthenoteratozoospermiaOC OrganochlorineOCDD 1,2,3,4,6,7,8,9-Osctachlorodibenzo-p-dioxinOCTNs Organic cation transportersOECD Organization for Economic Cooperation and Development•OH Hydroxyl radical6-OHDA 6-Hydroxydopamine8-OHdG 8-Hydroxy-2′-deoxyguanosine8-OHG 8-Hydroxyguanosine4-ONE 4-Oxo-trans-2-nonenalONOO− Peroxynitrite anionORAC Oxygen radical absorbance capacity8-oxodG 8-Hydroxy-2′-deoxyguanosineP13K Phosphatidylinositol 3-kinasep38MAPK p38 mitogen-activated protein kinasePAF Platelet-activating factorPAH Polycyclic aromatic hydrocarbonsPAI-1 Plasminogen activator fibrinogen inhibitor-1PARP Poly (ADP-ribose) polymerasePb LeadpBD-1 Porcine beta-defensin 1PBDEs Polybrominated diphenyl ethersPCBs Polychlorinated biphenylsPCDDs Polychlorinated dibenzodioxinsPCDFs Polychlorinated dibenzofuransPCNA Proliferating cell nuclear antigenPCOS Polycystic ovarian syndromePD Parkinson’s diseasePDGF Platelet-derived growth factorPDX-1 Pancreas duodenum homobox-1PEITC Phenylethyl isothiocyanatePEPCK Phosphoenolpyruvate carboxykinasePERK Protein kinase-like endoplasmic reticulum kinasePG Propyl gallatePGC-1α Peroxisome proliferator-activated receptor gamma coactivator 1-alphaPGE2 Prostaglandin E2PGI2 ProstacyclinPGI2 Prostaglandin I2PI3K Phosphatidylinositol 3-kinasePKA Protein kinase A

List of Abbreviations

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PKB Protein kinase BPKC Protein kinase CPLA2 Phospholipase A2PM Particulate matterPMRS Plasma membrane redox systemPMS Premenstrual syndromePOPs Persistent organic pollutantsPPARγ Peroxisome proliferator-activated receptor gammaPRX PeroxiredoxinPSA Prostate-specific antigenPTP-1B Tyrosine protein phosphatase 1BPUFAs Polyunsaturated fatty acidsQR Quinone reductaseRDA Recommended daily allowanceRNS Reactive nitrogen speciesRO2• PeroxylRO2• Peroxyl radicalRO5 Lipinski’s five rulesROH AlcoholROOH HydroperoxidesROS Reactive oxygen speciesSAPKs Stress-activated protein kinasessAβPPα Amyloid precursor protein-αSe-OH SelenolesSGA Small for gestational ageSGLT Sodium-dependent glucose co-transporterSGLT2 Sodium-glucose co-transporter 2sHBG Sex hormone-binding globulinSIRT SirtuinSLC23A1 Sodium-dependent vitamin C transportersSO2 Sulfur dioxideSOCS Cytokine signaling proteinsSOD Superoxide dismutaseSPPB Short physical performance batterySREBP-1c Sterol regulatory element-binding protein 1cSTAT Signal transducer and activator of transcriptionsVCAM-1 Soluble vascular cell adhesion molecule-1SVCT Sodium-ascorbate co-transporterT2D Type 2 diabetesT2DM Type 2 diabetes mellitusTAC Total antioxidant capacityTAS Total antioxidant statusTBA Thiobarbituric acidTBARS Thiobarbituric acid-reducing substancesTBHQ Tertiarybutyl hydroquinone

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TCDD 2,3,7,8-Tetrachlorodibenzo-p-dioxinTCS TriclosanTEAC Trolox equivalent antioxidant capacityTLC Thin-layer chromatographyTLR Toll-like receptorTNF-α Tumor necrosis factor alphaTOS Total oxidant statusTPP+ Tetraphenylphosphonium cationTRAP Total radical-trapping parameterTRAP Total reactive antioxidant potentialTRX ThioredoxinsTRXR Thioredoxin reductasesα-TTP α-Tocopherol transport proteinTXA2 Thromboxane A2Tyr10 Tyrosine 10UC Ulcerative colitisUCP-2 Uncoupling protein 2UDP-GT UDP-glucuronosyltransferaseUL Tolerable upper intakeUN United NationsuPA Urokinase plasminogen activatorUS United StatesUSDA United States Department of AgricultureUV UltravioletV VanadiumVCAM-1 Vascular cell adhesion molecule 1VEGF Vascular endothelial growth factorVLDL Very-low-density lipoproteinWASH 1 Warfarin/Aspirin Study in Heart failureWHO World Health OrganizationXO Xanthine oxidaseXOR Xanthine oxidoreductaseXRE Xenobiotic response elementZn Zinc

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Editor’s Biography

Kaïs Hussain Al-Gubory is senior researcher and engineer at the National Institute for Agricultural Research in France. After receiving his undergradu-ate degree in zoology, microbiology, and biochemis-try at the University of Baghdad (Iraq) with a First-Class Honours degree, he worked as an assis-tant lecturer at the same university. Supports from the Ministry of Higher Education and Scientific Research (Iraq), the National Institute for Agricultural Research, and the Medical Research Foundation (France) encouraged him to pursue a

postgraduate education, with completion of a DEA degree (Diplôme d’Etudes Approfondie), a PhD (Doctorat de Troisième Cycle), and a higher education degree of PhD (Thèse de Doctorat d’Etat ès Sciences Naturelles) at the University of Rennes (France). Al-Gubory’s career in research has focused on reproductive physi-ology where he studies the interactions between reproductive hormones and their target organs. He was the first to isolate and purify the superoxide dismutase from sheep corpus luteum of pregnancy and demonstrated the role played by this antioxi-dant enzyme in the control of ovarian-pituitary endocrine functions. He has made significant contributions to the understanding of the role of antioxidants in repro-duction and prenatal development. He was actively involved in the development of the fibered confocal fluorescence microscopy (Cell-viZio) for in vivo imaging of tissues and organs. This breakthrough in live cell imaging established a foundation for the consequent application of this technology in biomedical imaging and clini-cal studies. Dr. Al-Gubory’s current research interests include examining the impact of environmental factors on early life development and the beneficial effects of plant antioxidant compounds in prenatal development, with the aim of health

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promotion and prevention of early life programming diseases via modulation of oxidative stress. Dr. Al-Gubory has over 90 peer-reviewed publications, book chap-ters, communications, and reports.

Selected PublicationsAl-Gubory KH. Multiple exposures to environmental pollutants and oxidative

stress: Is there a sex specific risk of developmental complications for fetuses? Birth Defects Res C Embryo Today. 2016;108:351–64.

Al-Gubory KH, Garrel C. Sex-specific divergence of antioxidant pathways in fetal brain, liver, and skeletal muscles. Free Radic Res. 2016;50:366–73.

Al-Gubory KH. Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development. Reprod Biomed Online. 2014;29:17–31.

Al-Gubory KH. Mitochondria: omega-3 in the route of mitochondrial reactive oxygen species. Int J Biochem Cell Biol. 2012;44:1569–73.

Garrel C, Alessandri JM, Guesnet P, Al-Gubory KH.  Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development. Int J Biochem Cell Biol. 2012;44:123–31.

Al-Gubory KH, Houdebine LM. In vivo imaging of green fluorescent protein-expressing cells in transgenic animals using fibred confocal fluorescence micros-copy. Eur J Cell Biol. 2006;85:837–45.

Al-Gubory KH. Fibered confocal fluorescence microscopy for imaging apop-totic DNA fragmentation at the single-cell level in  vivo. Exp Cell Res. 2005;310:474–81.

Ismail Laher is professor of pharmacology in the Department of Pharmacology and Therapeutics in the Faculty of Medicine at the University of British Columbia (UBC) in Vancouver, Canada. He is also a visiting professor in the Department of Pharmacology in the Faculty of Medicine at the University of Vermont (USA). After receiving his undergraduate degree in pharmacology at Chelsea College (University of London, UK), he continued with graduate studies in cardiovascular pharmacology at Memorial University and UBC (Canada). Following

several years at the University of Vermont, he returned to UBC.  Ismail Laher’s research is in understanding resistance artery function in health and disease. He has edited a five-volume collection Systems Biology of Free Radicals and Antioxidants (Springer-Verlag, 2014). The major research interest/expertise of Professor Laher includes studies of the regulation of vascular function by oxidative stress in an ani-mal model of sleep apnea and of the effects of exercise in modulating oxidative stress in an animal model of type 2 diabetes. Professor Laher has published over 150 peer-reviewed articles and several book chapters on autonomic pharmacology, myogenic regulation of small arteries, and functional characterization of vascular function in animal models of disease (diabetes, hypertension, obesity, sleep apnea, spinal cord injury). He also serves on the editorial board of several journals.

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Selected PublicationsBadran M, Golbidi S, Ayas N, Laher I. Nitric oxide bioavailability in obstructive

sleep apnea: interplay of asymmetric dimethylarginine and free radicals. Sleep Med. 2015;2015:387801.

Laher I, Beam J, Botta A, Barendregt R, Sulistyoningrum D, Devlin A, Rheault M, Ghosh S. Short-term exercise worsens cardiac oxidative stress and fibrosis in 8-month old db/db mice by depleting cardiac glutathione. Free Radic Res. 2013;47:44–54.

Andriantsitohaina R, Auger C, Chataigneau T, Etienne-Selloum N, Li H, Martinez MC, Schini-Kerth VB, Laher I. Molecular mechanisms of the cardiovas-cular protective effects of polyphenols. Brit J Nutr. 2012;108:1532–49.

Golbidi S, Laher I. Antioxidant therapy in human endocrine disorders. Med Sci Monit. 2010;16:RA9–RA24.

Ghosh S, Khazaei M, Moien-Afshari F, Ang LS, Granville DJ, Verchere CB, Dunn SR, McCue P, Mizisin A, Sharma K, Laher I. Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal dis-ease in db/db mice. Am J Physiol Renal Physiol. 2008;296:F700–8.

Moein-Afshari F, Ghosh S, Khazai M, Keiffer T, Brownsey RW, Laher I. Exercise restores endothelial function independent of weight loss, hyperglycemic status or lipid profile in db/db mice. Diabetologia. 2008;51:1327–37.

Liang W, Tan CY, Ang L, Granville DJ, Wright JM, Laher I. Ramipril improves oxidative stress-related vascular endothelial dysfunction in db/db mice. J Physiol Sci. 2008;58:405–11.

About the Editors