Handbook of Synthetic Antioxidants

465 Pages·1997·45.581 MB·\465

by  Lester Packer (Editor)

Handbook
of
Synthetic
Antioxidants
ANTIOXIDANTS IN HEALTH AND DISEASE
Series Editors
LESTER PACKER, PH.D.
University of California
Berkeley, California
JURGEN FUCHS, PH.D., M.D.
Johann Wolfgang Goethe University
Frankfurt, Germany
1. Vitamin A in Health and Disease, edited by Rune Blomhoff
2. Biothiols in Health and Disease, edited by Lester Packer and
Enrique Cadenas
3. Handbook of Antioxidants, edited by Enrique Cadenas and Lester
Packer
4. Handbook of Synthetic Antioxidants, edited by Lester Packer
and Enrique Cadenas
Additional Volumes in Preparation
Vitamin C in Health and Disease, edited by Lester Packer and
Jurgen Fuchs
Lipoic Acid in Health and Disease, edited by Jurgen Fuchs,
Lester Packer, and Guido Zimmer
Related Volumes
Vitamin E in Health and Disease: Biochemistry and Clinical Appli
cations, edited by Lester Packer and Jurgen Fuchs
Free Radicals and Oxidation Phenomena in Biological Systems,
edited by Marcel Roberfroid and Pedro Buc Calderon
Handbook
of
Synthetic
Antioxidants
edited by
Lester Packer
University of California
Berkeley, California
Enrique Cadenas
University of Southern California
School of Pharmacy
Los Angeles, California
Boca Raton London New York
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Series Introduction
In June of 1992, 17 international researchers in the field of free radical and
antioxidant biology and preventive medicine met at the village of Saas Fee,
Switzerland, and drew up the Saas Fee Declaration to recognize the importance
of prevention in medicine and health. Since then, hundreds of researchers from
around the world have signed the declaration:
Saas Fee Declaration
On the significance of antioxidants in preventive medicine.
1. The intensive research on free radicals of the past 15 years by scientists world
wide has led to the statement in 1992 that antioxidant nutrients may have ma
jor significance in the prevention of a number of diseases. These include cardio
vascular and cerebrovascular disease, some forms of cancer and several other
disorders, many of which may be age-related.
2. There is now general agreement that there is a need for further work at the
fundamental scientific level, as well as in large-scale randomized trials and in
clinical medicine, which can be expected to lead to more precise information
being made available.
3. The major objective of this work is the prevention of disease. This may be
achieved by use of antioxidants which are natural physiological substances. The
strategy should be to achieve optimal intakes of these antioxidant nutrients as part
of preventive medicine.
iii
iv Series Introduction
4. It is quite clear that many environmental sources of free radicals exist, such as
ozone, sunlight, and other forms of radiation, smog, dust, and other atmospheric
pollutants. The optimal intake of antioxidants provides a preventive measure
against these hazards.
5. There is a great need for improvement in public awareness of the potential pre
ventive benefits of antioxidant nutrient intake. There is overwhelming evidence
that the antioxidant nutrients such as vitamin E, vitamin C, carotenoids, alpha
lipoic acid and others are safe even at very high levels of intake.
6. Moreover, there is now substantial agreement that governmental agencies, health
professionals and the media should promote information transfer to the general
public, particularly when evidence exists that benefits for human health and
public expenditure are overwhelming.
This declaration arose from the overwhelming evidence now available indi
cating that antioxidants play a critical role in wellness, health maintenance, and
the prevention of chronic and degenerative diseases. Antioxidants neutralize free
radicals that are generated during normal metabolism and during exposure to
environmental insult. Free radicals play a role in most major health problems
of the industrialized world, including cardiovascular disease, cancer, and dis
orders of aging.
Some antioxidants are quite familiar as vitamins or vitamin-forming corn
pounds: vitamin E, vitamin C, and the carotenoids, including beta-carotene.
These antioxidants must be constantly replenished through the diet. Others, such
as ubiquinols and the thiol antioxidants, including glutathione and lipoic acid,
are manufactured by the body, but the levels of many of these can be bolstered
through dietary supplementation. Until recently, it was thought that each anti
oxidant played its role in isolation from the others. But work in several labo
ratories indicates that there is a dynamic interplay among the systems. For ex
ample, when vitamin E neutralizes a free radical in a membrane, it becomes
itself a relatively harmless free radical, which decomposes. However, vitamin
C can regenerate vitamin E from the vitamin E radical, in effect "recycling"
vitamin E. Vitamin E becomes a radical in the process, but it, too, can be
recycled by interacting with other antioxidant systems. It has been shown that
these interactions occur in the test tube, and nutritional supplementation stud
ies support this idea for the whole organism. Thus, a picture is emerging of a
complex interplay among the defense systems, with the various antioxidant
cycles acting to prevent cell damage and disease. Out knowledge is far from
complete but these findings already have implications in terms of recommen
dations for supplementation.
Hence, it seems particularly appropriate to offer this series at the present
time. Never has the demand for knowledge about antioxidants been greater, and
never has their potential for treating disease and improving health been clearer.
The series highlights natural antioxidants and artificial antioxidants that mimic
natural systems.
Series Introduction v
Synthetic antioxidants, either of natural sources or designed to mimic bio
logical antioxidant systems, are proving to be of great value. Some are drugs
that are effective in therapy. Others may be useful in bolstering the body's
natural antioxidant systems by carefully designing biological mimics of natu
ral antioxidants.
Synthetic antioxidants are an area of research actively being pursued by phar
macologists, physiologists, biochemists, and cell biologists seeking to find new
and better means to enhance antioxidant defenses, particularly under conditions
of environmental and/or oxidative stress diseases. This remains an activity that
will undergo many new developments in the future, as more and more we tum
to the use of such substances in therapy for human disorders and for biotech
nological purposes.
Lester Packer
Jurgen Fuchs

Preface
The recognition of the involvement of oxygen radicals in several pathologies
has led to the implementation of antioxidant therapy. Dietary nutrients with
antioxidant properties are assuming great significance in the context of certain
pathologies, such as atherosclerosis. In a classical sense, vitamin E is the pro
totype antioxidant with a probable role in therapeutic regimes directed toward
oxidative stress-mediated diseases.
Synthetic antioxidants are of potential use in chemistry, the food industry,
and medicine. Some of these compounds retain a functional group chemistry
analogous to that of "natural" antioxidants and introduce new chemical groups
that enhance their range of cellular action or make them available to cell sites
hitherto restricted. Alternatively, some synthetic antioxidants bear no structural
analogy with natural antioxidants and exhibit a high reactivity toward reactive
oxygen species and/or display selective protection in certain tissues.
Despite the overwhelming number of reports on synthetic antioxidants, no
treatise exists that deals with the chemical, biological, medical, and industrial
aspects of these compounds. Likewise, a comprehensive and systematic clas
sification of synthetic antioxidants is missing. This book, which is a sequel to
Handbook of Antioxidants (edited by Enrique Cadenas and Lester Packer),
covers these aspects. The chapters provide a rationale for a classification of
synthetic antioxidants, and each group is surveyed exhaustively from the physi-
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