Table Of ContentTrace Elements,
Micronutrients, and Free Radicals
Contemporary Issues
in Biomedicine, Ethics, and Society
Trace Elements, Micronutrients, and Free Radicals,
editedbyIvorE. Dreosti, 1991
Beyond Baby M: Ethical Issues in New Reproductive
Techniques, editedbyDianneM. Bartels,Reinhard
Priester,DorothyE.Vawter, andArthurL.Caplan, 1989
Reproductive Laws for the 1990s,editedby Sherrill
Cohen and Nadine Taub, 1989
The Nature ofClinical Ethics,editedbyBarryHoffmaster,
Benjamin Freedman, and Gwen Fraser, 1988
What Is a Person?, editedbyMichael F. Goodman, 1988
Advocacy in Health Care, editedby Joan H. Marks, 1986
Which Babies Shall Live?, editedbyThomas H. Murray
andArthurL. Caplan, 1985
Feeling Good and Doing Better,editedby Thomas H.
Murray, Willard Gaylin, and Ruth Macklin, 1984
Ethics and Animals, editedbyHarlan B. Miller
and William H. Williams, 1983
Profits and Professions, editedby Wade L. Robison,
Michael S. Pritchard, andJoseph Ellin, 1983
Visions ofWomen, editedby Linda A. Bell, 1983
Medical Genetics Casebook,by Colleen Clements, 1982
Who Decides?,editedbyNora K. Bell, 1982
The Custom-Made Child?, editedbyHelen B. Holmes,
Betty B. Hoskins, andMichael Gross, 1980
Medical Responsibility, editedby Wade L. Robison
andMichael S. Pritchard, 1979
ContemporaryIssues inBiomedicalEthics,editedbyJohn
W. Davis,BarryHoffmaster, and Sarah Shorten, 1979
Trace Elements,
Micronutrients,
and Free Radicals
Edited by
Ivor E. Dreosti
Division of Human Nutrition, CSIRO, Adelaide, Australia
Springer Science+Business Media, LLC
Copyright ©1991 Springer Science+Business Media New York
Originally published by Humana Press Inc. in 1991
Softcover reprint of the hardcover 1s t edition 1991
All rights in any form whatsoever reserved.
No part of this book may be reproduced, stored in a retrieval system, or
transmitted in any form or by any means (electronic, mechanical, photocopying,
microfilming, recording, or otherwise) without written permission from the pub
lisher.
Library of Congress Cataloging-In· Publication Data
Trace elements, micronutrients, and free radicals I edited by Ivar E.
Dreosti.
p. cm.
Includes bibliographical references and index.
ISBN 978-1-4612-6754-6 ISBN 978-1-4612-0419-0 (eBook)
DOI 10.1007/978-1-4612-0419-0
1. Free radicals (Chemistry)-Physiological effect. 2. Active
oxygen; in the body. 3. Trace elements in human nutrition.
I. Dreosti, Ivor E.
RB170.T73 1991
612'.01524-dc20 91-13721
CIP
Preface
Itisonlyrecentlythatthenaturaloccurrenceoffreeradicalsin
biological tissue has become widely accepted, and that the suspi
cion with which biologists previously viewed the free radicals of
radiationchemistryhasbeenplacedinabroaderperspective. Now,
oxygen-derivedfreeradicals areconsideredrespectable biochemi
cal intermediates, given always the caveat that unwanted tissue
damage may arise if these active species are produced in such
abundance that they overwhelm the natural antioxidant and free
radical defense mechanisms, or if these systems have become
hypoeffective. Many factors, including several dietary manipula
tions,canleadtoelevatedproductionofsuperoxideandmayresult
in free radical overload, whereasa deficiency ofthose micronutri
ents associated with the antioxidant defense mec.hanisms may re
sultin substantiallydiminished antioxidantcapacity.
Bynow, antioxidants have become a household wordand al
mosteveryoneis aware oftheirimponancein protecting the body
againstattack by activeoxygen species. Indeed, itis a paradox of
nature thatoxygen, whichis soessential to sustain aerobiclife, ul
timately contributes to its destruction. Not surprisingly, recogni
tionofthisdilemmahas generateda spateofantioxidant strategies
intended to reduce the risk of tissue damage by rampant oxygen
radicals, some sadly based less on science than on speculation.
Nevenheless, it is clear that free radical damage occurs continu
ouslyinaerobicorganismsandthatcomplexdefensesystemsexist
to minimizeit. Also, therecan be noquestion concerning the sig
nalcontributionmade by severalmicronutrients tothesedefenses,
nor about the participation offree radicals in the pathogenesis of
severaldegenerativediseases inhumans-although muchremains
unanswered. At a nutritional level, itis now well established that
dietaryintakesoftheantioxidantmicronutrientsatlevelsbelowthe
v
vi Preface
requirementwillraise theriskoffree radicaldamage, although the
value of massive supplementation of these dietary factors in the
pursuitofsupranormalhealth has not been proven.
Thepresentvolumeaddressestheissueoffreeradicaldamage
and micronutrient protection in humans and animals, and seeks to
bridge the gap between the separate disciplines of free radical
chemistry, cellularbiology, and micronutrientnutrition in orderto
provide the broader basis from which the suggested roles ofpro
and antioxidants in humandisease and aging will need to be stud
ied. Emphasishasbeenplacedprimarilyonfundamental scientific
aspectsofthequestionrather thanon thepossible useofmicronu
trients as therapeutic agents for the treatment ofhuman disorders.
Nevertheless,recognizing that this objective may well represent a
substantialgoalinantioxidantresearch, severallaterchaptershave
includedsomediscussionofthese matters.
It is our hope that this volume will provide acomprehensive
and currentdiscussion ofthe roleofmicronutrients in antioxidant
protection,andwetrustthatitwill,forsometimeatleast,providea
vade mecumfor those scientists working in, orentering this excit
ing new researcharea. Weacknowledge withpleasure and thanks
theparticipationofourdistinguishedpanelofcontributors and the
supportofTheHumanaPress.
E. Dreosti
[VOT
Contents
v Preface
lvorE. Dreosti
1 1 • Free Radicals in Biological Systems
Martyn C. R. Symons
25 2. Free Radicals as Mediators ofTissue Injury
Rolando DelMaestro
53 3 • Free Radical Biology ofIron
Christine C. Winterbourn
77 4 • Dietary Prooxidants
Mario Umberto Dianzani
107 5. EssentialTrace Elements in Antioxidant Processes
Sheri Zidenberg-CherrandCarl L. Keen
129 6. Vitamins and Related Dietary Antioxidants
Ching K. Chow
149 7. Free Radical Pathology and the Genome
lvorE. Dreosti
171 8· The Role ofFree Radicals in Cancer and Aging
T. Mark Florence
199 9. Free Radicals and Malnutrition
Michael H. N. Golden, Dan D. Ramdath,
andBarbara E. Golden
223 Conclusions
lvorE. Dreosti
227 Index
vii
Contributors
Ching K. Chow • Department of Nutrition and Food Science,
University ofKentucky, Lexington, KY
Rolando Del Maestro • BrainResearch Laboratories, University
ofWestern Ontario, Ontario, Canada
Mario Umberto Dianzani • Institute of General Pathology,
University ofTurin, Turin, Italy
lvorE. Dreosti·DivisionofHumanNutrition,CSIRO,Adelaide,
Australia
T. Mark Florence • Division of Energy Resources, CSIRO,
Adelaide, Australia (currently with the Centre for Envi
ronmental and Health Sciences)
Barbara E. Golden •TropicalMetabolism Research Unit, Uni
versity ofthe WestIndies, Kingston, Jamaica
Michael H. N. Golden· Tropical Metabolism Research Unit,
University ofthe West Indies, Kingston, Jamaica
CarlL. Keen •DepartmentofNutrition, UniversityofCalifornia,
Davis, CA
Dan D. Ramdath • University of the West Indies, Kingston,
Jamaica
Martyn C. R. Symons •DepartmentofChemistry, The Univer
sity, Leicester, United Kingdom
Christine C. Winterbourn • Department of Pathology,
Christchurch Hospital, Christchurch, New Zealand
Sheri Zidenberg-Cherr • Department of Nutrition, University
ofCalifornia, Davis, CA
viii
CHAPTER 1
Free Radicals
in Biological Systems
C. R.
MARTYN SYMONS
ABSTRACT
In this introductory chapter, the nature of 'free radicals' is dis
cussed, and methods for detection and identification are outlined,
with particular reference to electron spin resonance (ESR) spectro
scopy. Common methods for generating radicals are summarized.
A range of simple inorganic radicals of particularbiological sig
nificance are discussed, including the oxygen radicals, O2-, H02.
and OH·. The use of spin-traps in ESR studies of these species is
outlined. Afterdiscussingafew importantorganicradicals, thechap
ter finishes with a brief review of nitroxide radicals and their uses.
1. BACKGROOND
This is an introductory chapter for those not well versed in the
chemistryandphysicsofradicals. Istartbyattemptingadefinitionofthe
term, followed by a very brief backward view, and an outline of the
techniqueofelectronspin resonance(ESR), whichisuniquelyrelevantto
the study of radicals.
My aim is to present an overview that, I hope, enlightens subse
quentchapters. Obviously, itis not inanysenseexhaustive. Iincludean
outline of ESR spectroscopy because of its central importance, and be
cause it has been one of my major interests over the past 30 yr.
1
2 Symons
1.1. What Is a Free Radical?
The term "free" has only historical significance and can be dropped
with impunity. A broad definition ofa radical is that it is a molecule or
ion containing an unpaired electron. The significance of this can be
gauged in a simple way by considering reaction [1]. Here R· and R·' are
R· + R·' =; R-R [1]
I
radicals, thedots signifyingunpairedelectrons. Thesehave pairedin the
bond between the groups in R-R', which isa normal molecule. Whereas
most radicals are reactive and undergo dimerization, or other reactions,
inwhichtheunpairedelectronsbecomepaired, somearerelativelystable
and have long life-times. These include nitroxide radicals, R NO, and a
2
range of radicals and radical-ions in which the unpaired electron is so
delocalized that it is unwilling to participate in a localized electron-pair
bond. Thus, in a sense, the reactivity ofa radical lies in the desire of its
characteristic unpaired electron to participate in covalent (electron-pair)
bonding. Otherreactionsofgreatimportance that may precedereactions
of type [1] include [2] and [3] [Scheme I], that usually generate new
radicals that will ultimately be "destroyed" via reaction [1]. Sometimes,
someofthesenewspecieshavelonglifetimesandbecomereadilydetect
able, especially by ESR spectroscopy (see under "spin-trapping, Section
2.4), atothers, [2] or [3] may repeat via reactionsofR·' so thatone initial
radical triggers or initiates a series of radical steps before reaction [1]
occurs. This is called a chain reaction, and is highly characteristic of the
reaction of radicals. The very important autoxidation reaction, discussed
elsewhere, isakeybiologicalreactionthatowesitsimportancetoitschain
nature.
1.2. ESR Spectroscopy: A Unique Tool
Clearly, unpaired electrons (broken bonds) are the key to radical
chemistry. It is therefore helpful to consider some properties thereof.
Electron spinresonance (ESR) orelectron paramagneticresonance (EPR)
(these are the same thing) are spectroscopic techniques that literally
involve unpaired electrons and nothing else. So, if a spectrum is ob
tained, unpairedelectronsmustbepresent. Theconverse, unfortunately,
is not true as a generalization (see below) although a very large range of
radicals can be ruled out as major reactants if no signal is obtained. ESR
spectroscopy is extremely sensitive, and if the spectra comprise narrow
lines, concentrations as lowas 10-7gm rads A-I canbedetected. Abrief
overviewofthewayESRworksandofhowitcanbeused toidentifyand
estimate various radicals is given in Section 2c.
