A
New Concept in Nutrition
There are
proven benefits from compounds called proanthocyanidins
(OPCs) that are highly concentrated in grape seeds.
"Free
Radicals have been implicated in over a hundred disease
conditions in humans"
...including
arthritis, hemorrhagic shock, atherosclerosis, advancing age,
ischemia and reperfusion injury of many organs, Alzheimer and
Parkinson's disease, gastrointestinal dysfunctions, tumor
promotion and carcinogenesis, and AIDS.Antioxidants are
potent scavengers of free radicals and serve as inhibitors of
neoplastic processes." (Toxicology
2000 Aug 7;148(2-3):187-97)
"Evidence is
accumulating that most of the degenerative diseases that
afflict humanity have their origin in deleterious free
radical reactions."
(Florence
TM, Centre for Environmental and Health Science Pty Ltd,
Sydney, NSW. "The role of free radicals in disease", ust N Z
J Ophthalmol 1995 Feb;23(1):3-7)
Antioxidants
-
are important supplements
required in our diet to neutralize, scavenge, and
eliminate from the body, free radical molecules before
they can do serious damage to our tissues and organs. Free
radicals are unstable molecules which attack DNA and
mitochondria, the basic building blocks of all tissues,
thereby impairing the functional health of membranes and
organs. This damage impedes the replication of healthy
cellular material throughout the body and leads to
premature aging. Free radicals are implicated in the
causation of over 60 degenerative diseases.
~
Omega Biotech
Studies
ar1
The Power of Grape Seed Extract
By Michael Murray, N.D. http://my.webmd.com/content/dmk/dmk_article_5462836
ar2
Journal of the Science of Food and
Agriculture
Volume 80, Issue 7, 2000. Pages: 1094-1117
Proanthocyanidins and tannin-like compounds - nature,
occurrence, dietary intake and effects on nutrition and health
(Special Issue: Nutritional
Enhancement of Plant-based Food in European Trade (NEODIET).
Issue Edited by DG Lindsay, MN Clifford.)
"...As metal ion chelators, they influence the bioavailability
of several minerals... As reducing agents, they may participate
in the prevention of cancers, both of the digestive tract and
inner organs. They may also protect LDLs against oxidation and
inhibit platelet aggregation and therefore prevent
cardiovascular diseases."\
ar3
Altern Med Rev 2000
Apr;5(2):144-51
Oligomeric proanthocyanidin complexes: history, structure, and
phytopharmaceutical applications.
Fine AM
International Clinical Research Center, Scottsdale, AZ 85260,
USA.
"...OPCs are primarily known for their antioxidant activity.
However, these compounds have also been reported to demonstrate
antibacterial, antiviral, anticarcinogenic, anti-inflammatory,
anti-allergic, and vasodilatory actions. In addition, they have
been found to inhibit lipid peroxidation, platelet aggregation,
capillary permeability and fragility, and to affect enzyme
systems including phospholipase A2, cyclooxygenase, and
lipoxygenase. Based on these reported findings, OPCs may be a
useful component in the treatment of a number of conditions."
ar4
J Gerontol 1980
Jan;35(1):45-56
Aspects of free radical reactions in biological systems:
aging.
Leibovitz BE, Siegel BV
"...Free radicals are produced during mitochondrial respiration,
during the autooxidation of a variety of biological molecules
and chemicals, during irradiation damage, and are found as
environmental pollutants. Free radicals induce lipid
peroxidation which results in membrane damage, increased
disulfide/sulfhydryl ratios, and accumulation of aging pigments.
Superoxide dismutase, glutathione peroxidase, vitamin E, vitamin
C, and selenium are of importance with respect to free radical
and lipid peroxide quenching. During aging, the levels of
vitamin C appear to decline in the human, guinea pig, and the
mouse. Synthetic antioxidants, added to the diets of mice, have
been noted to extend the lifespan and mean half-survivale times.
ar5 Toxicology 2000
Aug 7;148(2-3):187-97
Free radicals and grape seed proanthocyanidin extract:
importance in human health and disease prevention.
Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA,
Joshi SS, Pruess HG
Department of Pharmaceutical and Administrative Sciences,
Creighton University School of Pharmacy & Allied Health
Professions, 2500 California Plaza, Omaha, NE 68178, USA.
Free radicals have been implicated in over a hundred disease
conditions in humans, including arthritis, hemorrhagic shock,
atherosclerosis, advancing age, ischemia and reperfusion injury
of many organs, Alzheimer and Parkinson's disease,
gastrointestinal dysfunctions, tumor promotion and
carcinogenesis, and AIDS. Antioxidants are potent scavengers of
free radicals and serve as inhibitors of neoplastic processes.
These experiments demonstrated that GSPE is highly bioavailable
and provides significantly greater protection against free
radicals and free radical-induced lipid peroxidation and DNA
damage than vitamins C, E and beta-carotene. GSPE was also shown
to demonstrate cytotoxicity towards human breast, lung and
gastric adenocarcinoma cells, while enhancing the growth and
viability of normal human gastric mucosal cells... GSPE provided
significantly better protection as compared to vitamins C and E,
singly and in combination. GSPE also demonstrated excellent
protection against acetaminophen overdose-induced liver and
kidney damage ... GSPE demonstrated excellent protection against
myocardial ischemia-reperfusion injury and myocardial infarction
in rats... Topical application of GSPE enhances sun protection
factor in human volunteers, as well as supplementation of GSPE
ameliorates chronic pancreatitis in humans.
ar6 J
Basic Clin Physiol Pharmacol 1995;6(3-4):205-28
The role of free radicals in toxicity and disease.
Stohs SJ
Free radicals...are responsible for the tissue damaging effects
as lipid peroxidation, and DNA and protein damage. Oxidative
stress associated with production of reactive oxygen species is
believed to be involved not only in ... the pathophysiology of
aging, and various age-related diseases, including cataracts,
atherosclerosis, neoplastic diseases, diabetes, diabetic
retinopathy, chronic inflammatory diseases of the
gastrointestinal tract, aging of skin, diseases associated with
cartilage, Alzheimer's disease, and other neurologic disorders.
ar7
Free radicals, antioxidants and preventive geriatrics.
ar7Ward J
Aged Care Services, Eastern Sydney Area Health Service,
Pagewood, New South Wales.
Free radical damage seems likely to be significant in the
pathophysiology of atherosclerosis, ischaemia-reperfusion
injury, Parkinson's disease, cataract, some cancers and
rheumatoid arthritis. Evidence to suggest a protective effect
from antioxidant vitamins exists for ischaemic heart disease,
cataract and some cancers.
ar8
Int J Clin Lab Res 1999;29(2):49-55
An update on the role of free radicals and antioxidant defense
in human disease.
Vendemiale G, Grattagliano I, Altomare E
Department of Internal and Occupational Medicine, University of
Bari - Medical School, Piazza G. Cesare, II, I-70124 Bari,
Italy.
evidence indicates that free radicals play
ar8c important
roles in many physiological and pathological conditions. The
wider application of free radical measurement has increased
awareness of functional implications of radical-induced
impairment of the oxidative/antioxidative balance. In the
following review, the role of oxygen free radicals in some human
and experimental pathological conditions is described, with
particular emphasis on the mechanisms by which they produce
oxidative damage to lipids, proteins, and nucleic bases. The
role of free radicals and the activation of the antioxidant
systems in arteriosclerosis and ageing, diabetes,
ischemia/reperfusion injury, ethanol intoxication, and liver
steatosis is discussed.
ar9
Am Pharm 1994
Sep;NS34(9):26-35
Oxygen free radicals and antioxidants: a review.
Barber DA, Harris SR
Department of Surgery, Mayo Clinic & Foundation, Rochester,
Minn.
two of every three people in this country die from either
cardiovascular disease or cancer. Based on both experimental and
epidemiological evidence, investigators believe that free
radicals play a critical role in the development of both
diseases. Low levels of antioxidants, which increases free
radical activity, are clearly associated with an increased risk
of these diseases. This link has led to the conclusion that use
of antioxidant vitamin supplements to scavenge free radicals
could potentially decrease the risks of cancer and
cardiovascular disease
ar10
Ceska Slov Farm 1996
Nov;45(6):296-301
Natural substances with antioxidant activity
Spilkova J, Dusek J
Katedra farmakognozie Farmaceuticke fakulty Univerzity
Karlovy, Hradec Kralove.
substances of phenolic nature (flavonoids, hydroxycinnamic
acids, tannins), in which antioxidant effects and ability to
quench free radicals have been demonstrated. A number of
substances seem to be perspective in the treatment of
cardiovascular diseases, cancer and liver diseases.
ar11
Journal of the Science of Food and
Agriculture
Volume 80, Issue 7, 2000. Pages:
1094-1117
Proanthocyanidins and tannin-like compounds - nature,
occurrence, dietary intake and effects on nutrition and health
Proanthocyanidins ... form stable complexes with metal ions and
with proteins and are, like other polyphenols, good reducing
agents. Many of their biological effects of nutritional interest
derive from these properties. As metal ion chelators, they
influence the bioavailability of several minerals. The
nutritional significance of the non-specific complexation of
proteins is less clear. As reducing agents, they may participate
in the prevention of cancers, both of the digestive tract and
inner organs. They may also protect LDLs against oxidation and
inhibit platelet aggregation and therefore prevent
cardiovascular diseases.
ar12J Agric Food Chem 1999
May;47(5):1892-7
Increase of antioxidative potential of rat plasma by oral
administration of proanthocyanidin-rich extract from grape
seeds.
Koga T, Moro K, Nakamori K, Yamakoshi J, Hosoyama H, Kataoka
S, Ariga T
Noda Institute for Scientific Research, Chiba, Japan.
"...Proanthocyanidins... increases the resistance of blood
plasma against oxidative stress and may contribute to
physiological functions through their in vivo antioxidative
ability."
ar13
Phytotherapy Research
Volume 12, Issue 8, 1998. Pages:
568-571
Hydrogen peroxide-induced modulation of intracellular oxidized
states in cultured macrophage J774A.1 and neuroactive PC-12
cells, and protection by a novel grape seed proanthocyanidin
extract
D. Bagchi 1, C. Kuszynski 2, J. Balmoori 1, M. Bagchi 1, S. J.
Stohs 1 *
1Departments of Pharmaceutical and Administrative Sciences, and
Pharmacology, Creighton University Health Sciences Center,
Omaha, NE 68178, USA
2University of Nebraska Medical Center, Omaha, NE 68198, USA
grape seed proanthocyanidin extract (GSPE) with respect to their
scavenging abilities against biochemically generated free
radicals in both in
vitro and in
vivo models.
The results demonstrated that GSPE is a significantly more
potent oxygen free radical scavenger compared with vitamins C
and E and -carotene. GSPE has been reported to exhibit a wide
range of biological and pharmacological activities including
free radical scavenging, antibacterial, antiviral,
antiinflammatory, antiallergic and vasodilator actions.
GSPE can significantly protect against hydrogen peroxide-induced
oxidative stress in cultured J774A.1 macrophage and neuronal
PC-12 cells.
ar14
Nutr Clin Pract 1995
Feb;10(1):19-25
Role of antioxidants in health maintenance.
Sardesai VM
Free radicals are produced in the body as by products of normal
metabolism and as a result of exposure to radiation and some
environmental pollutants. Because they are highly reactive, they
can damage cellular components and are implicated in a variety
of diseases. Free radicals are normally neutralized by efficient
systems in the body that include the antioxidant enzymes
(superoxide dismutase, catalase, and glutathione peroxidase) and
the nutrient-derived antioxidant small molecules (vitamin E,
vitamin C, carotenes, flavonoids, glutathione, uric acid, and
taurine). In healthy individuals, a delicate balance exists
between free radicals and antioxidants. In some pathologic
conditions such as diabetes, and in critically ill patients,
oxidative stress causes the level of antioxidants to fall below
normal. Antioxidant supplements for such conditions are expected
to be of benefit.
ar15
Free radical tissue damage: protective role of antioxidant
nutrients.
Machlin LJ, Bendich A
Clinical Nutrition, Hoffmann-La Roche Inc., Nutley, New Jersey
07110.
Highly reactive molecules called free radicals can cause tissue
damage by reacting with polyunsaturated fatty acids in cellular
membranes, nucleotides in DNA, and critical sulfhydryl bonds in
proteins. Free radicals can originate endogenously from normal
metabolic reactions or exogenously as components of tobacco
smoke and air pollutants and indirectly through the metabolism
of certain solvents, drugs, and pesticides as well as through
exposure to radiation. There is some evidence that free radical
damage contributes to the etiology of many chronic health
problems such as emphysema, cardiovascular and inflammatory
diseases, cataracts, and cancer.
Based on the growing interest in free radical biology and the
lack of effective therapies for many of the chronic diseases,
the usefulness of essential, safe nutrients in protecting
against the adverse effects of oxidative injury warrants further
study.
ar16 Mater
Med Pol 1993
Jan-Mar;25(1):37-43
Free radicals and antioxidant systems.
Erenel G, Erbas D, Aricioglu A
Department of Physiology, Medical Faculty, Gazi University.
Free radicals are undesirable peroxides that have long been
implicated in several deleterious effects in our body including
aging process.
ar17
Nutritional support, free radicals, and antioxidants
Faintuch J, Aguilar PB, Dias MC, Nadalin W, Pinotti HW
Antioxidants and free radical scavengers are molecules
endowed with the ability of neutralizing reactive oxygen species
that may accumulate in the organism during various pathologic
processes. In circumstances of peroxidation of lipids and damage
to enzymatic chains, cell membranes and other structures may be
followed by functional losses and even cell death.
ar18
Role of free radicals, oxidative stress and antioxidant
systems in liver diseases
Jakus V, Lopuchova M
Dpt of Medical Chemistry, Biochemistry and Clinical
Biochemistry, Medical Faculty, Comenius University, Bratislava,
Slovakia. jakus@fmed.uniba.sk
Recent experimental findings suggest that free radicals and
oxidative stress play an important role in the pathogenesis of
alcoholic and toxic liver diseases and viral hepatitis. The
presented review summarizes knowledge on the pathomechanism of
free radical reactions in liver diseases and the results of
experimental observations of antioxidant systems and adjuvant
antioxidant pharmacotherapy. Some of the hepatoprotective drugs
have antioxidant activity and can produce such beneficial
effects as membrane stabilisation, neutralization of free
radicals and immunomodulation. Some liver diseases can be
successfully prevented or treated by supplementation with
antioxidant active substances of even plant origin.
ar19
Free radical scavenging by brain homogenate: implication to
free radical damage and antioxidant defense in brain.
Mori A, Liu J, Wang X, Kawai M
Department of Neuroscience, Okayama University Medical School,
Japan.
To study the mechanisms of free radical-induced brain damage and
the antioxidant defense in the brain
The ability of brain homogenate to scavenge free radicals
implies that brain damage can be induced by free radicals since
they are known to react virtually with any type of molecule such
as nucleic acids, membrane lipids, and proteins in the brain
ar20
Nutr Rev 1994
Aug;52(8 Pt 1):253-65
Free radicals and antioxidants: a personal view.
Halliwell B
Neurodegenerative Disease Research Center, University of London
King's College, UK.
The reactivity of different free radicals varies, but some can
cause severe damage to biological molecules, especially to DNA,
lipids, and proteins. Antioxidant defense systems scavenge and
minimize the formation of oxygen-derived species,
but they are not 100% effective. Hence, diet-derived
antioxidants may be particularly important in diminishing
cumulative oxidative damage and helping us to stay healthier for
longer. Repair systems exist to deal with molecules that have
been oxidatively damaged. Damage to DNA by hydroxyl radicals
appears to occur in all aerobic cells, and might be a
significant contributor to the age-dependent development of
cancer. Lipid peroxidation probably contributes significantly to
the development of atherosclerosis.
ar21 Indian
J Med Sci 1997
Sep;51(9):319-36
The free radicals--the hidden culprits--an update.
Ansari KN
M.L.N. Medical College, Allahabad.
Free radicals are capable of killing bacteria, damage
biomolecules, provoke immune response, activate oncogens, cause
atherogenesis and enhance ageing process. However, in healthy
conditions nature has endowed human body with enormous
antioxidant potential. Subtle balance exists between free
radical generation and antioxidant defence system to cope with
oxidative stress by various enzymes and vitamins at cellular
level which prevent the occurrence of disease. However, factors
tilting the balance in favour of excess free radicals generation
lead to widespread oxidative tissue damage and diseases.
Therefore, trouble starts when there is an excess of free
radicals and the defence mechanism lags behind. Overwhelming
production of free radicals in response to exposure to toxic
chemicals and ageing may necessitate judicious antioxidant
supplement to help alleviate free radical mediated damage.
ar22
Orv Hetil 1993
Mar 28;134(13):693-6
The role of free radical scavengers in gastrointestinal
diseases
Feher J, Pronai L
Semmelweis Orvostudomanyi Egyetem, Budapest, II., Belklinika.
Be it ever so complex the natural antioxidant scavenger system
of the organism, the protection provided by it seems to be
inappropriate in certain diseases of the gastrointestinal mucus
membrane, such as chronic inflammation, immune- and malignant
diseases of the bowel. Despite the wide range of therapeutic
attempts, the treatment of these diseases has not yet been
solved, and the anti-inflammatory-, immunomodulatory-,
cytostatic drugs currently used, have several side effects.
Therefore, the so called natural- and synthetic antioxidants
have been more widely employed for additional and adjuvant
treatment. It also has become clear that the direct free radical
scavenging effect and/or the membrane protection play an
important role in the action mechanism of several
old-established drugs. The recent report lists those natural and
synthetic antioxidants which have been successfully employed in
the clinical treatment of bowel diseases.
ar23
ust N Z J Ophthalmol 1995
Feb;23(1):3-7
The role of free radicals in disease.
Florence TM
Centre for Environmental and Health Science Pty Ltd, Sydney,
NSW.
Evidence
is accumulating that most of the degenerative diseases that
afflict humanity have their origin in deleterious free radical
reactions. These diseases include atherosclerosis, cancer,
inflammatory joint disease, asthma, diabetes, senile dementia
and degenerative eye disease. The process of biological ageing
might also have a free radical basis. Most free radical damage
to cells involves oxygen free radicals or, more generally,
activated oxygen species (AOS) which include non-radical species
such as singlet oxygen and hydrogen peroxide as well as free
radicals. The AOS can damage genetic material, cause lipid
peroxidation in cell membranes, and inactivate membrane-bound
enzymes. Humans are well endowed with antioxidant defences
against AOS; these antioxidants, or free radical scavengers,
include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E),
beta-carotene, coenzyme Q10, enzymes such as catalase and
superoxide dismutase, and trace elements including selenium and
zinc. The eye is an organ with intense AOS activity, and it
requires high levels of antioxidants to protect its unsaturated
fatty acids. The human species is not genetically adapted to
survive past middle age, and it appears that antioxidant
supplementation of our diet is needed to ensure a more healthy
elderly population.
ar24
Am J Clin Nutr 1991
Apr;53(4 Suppl):1050S-1055S
Protective role of vitamin E in biological systems.
Packer L
Department of Molecular and Cell Biology, University of
California, Berkeley 94720.
Vitamin E is well accepted as nature's most effective
lipid-soluble, chain-breaking antioxidant, protecting cell
membranes from peroxidative damage. Free-radical-mediated
pathology has been implicated in the development over time of
degenerative diseases and conditions. This paper reviews the
current research on the protective role and requirements for
vitamin E and the other antioxidants in preventing or minimizing
free-radical damage associated with specific diseases and
lifestyle patterns and processes, including cancer, aging,
circulatory conditions, arthritis, cataract, pollution, and
strenuous exercise. While awaiting results of further human
studies, research evidence suggests that an adequate intake of
vitamin E and the other antioxidants can provide protection from
the increasingly high free-radical concentrations caused by air
pollutants and current lifestyle patterns.
ar25
Proc Nutr Soc 1994
Jul;53(2):251-62
Vitamin E: molecular and biological function.
Burton GW
Steacie Institute for Molecular Sciences, National Research
Council of Canada, Ottawa, Ontario.
There is a growing body of evidence implicating free radicals in
a wide variety of medical diseases and conditions, especially
the diseases of ageing, such as cancer and cardiovascular
disease, which appear to be ultimate expressions of long-term,
cumulative and sustained cellular damage. Vitamin E is an
excellent lipid-soluble, chain-breaking antioxidant in the
presence of other co-operative antioxidants such as vitamin C or
ubiquinol, but it can act as a pro-oxidant in their absence.
Epidemiological findings and animal studies support the belief
that vitamin E is protective against cardiovascular disease and
possibly cancer. The wide range of symptoms associated with
vitamin E deficiency is consistent with a loss of antioxidant
protection in those long-lived cells in which there is
sufficient opportunity for accumulation of free radical damage.
The cellular damage is proposed to arise from the generation of
free radicals during normal aerobic metabolism. Some susceptible
tissues may have enhanced levels of radicals that are produced,
for example, by the action of cytochrome P-450 enzymes in
steroidogenic tissues, or by the generation of NO in neural
tissues.
ar26
Recenti Prog Med 1991
Jan;82(1):39-44
Free radicals in human pathology
Casaril M, Corso F, Corrocher R
Istituto di Patologia speciale medica, Universita, Verona.
The role of free radicals has been suggested in many
different diseases; the molecular mechanisms of radical-induced
damage have been widely investigated: the main effects on
cellular components are lipid peroxidation, protein denaturation
and DNA damage causing alteration in membrane functions,
impaired enzyme activity and genetic alterations, including
cancer. Since oxidative metabolism produces some radicals,
aerobic organisms acquired a complex defensive system against
radical attack, based on localization of oxidative reactions,
enzymes that scavenge free radicals or their products and
antioxidant vitamins. Diseases may arise from increased exposure
to radicals or from impaired efficiency of protective systems.
The role of oxygen radicals in cancerogenesis, alcoholic liver
disease and the aging process is also briefly discussed.
ar27
Int J Sport Nutr 1994
Sep;4(3):205-20
Free radicals, exercise, and antioxidant supplementation.
Kanter MM
Gatorade Sport Science Institute, Quaker Oats Company,
Barrington, IL 60010.
Free radicals have been implicated in the development of diverse
diseases such as cancer, diabetes, and cataracts, and recent
epidemiological data suggest an inverse relationship between
antioxidant intake and cardiovascular disease risk. Data also
suggest that antioxidants may delay aging. Research has
indicated that free radical production and subsequent lipid
peroxidation are normal sequelae to the rise in oxygen
consumption with exercise. Consequently, antioxidant
supplementation may detoxify the peroxides produced during
exercise and diminish muscle damage and soreness. Vitamin E,
beta carotene, and vitamin C have shown promise as protective
antioxidants. Other ingestible products with antioxidant
properties include selenium and coenzyme Q10. The role (if any)
that free radicals play in the development of exercise-induced
tissue damage, or the protective role that antioxidants may
play, remains to be elucidated. Current methods used to assess
exercise-induced lipid peroxidation are not extremely specific
or sensitive; research that utilizes more sophisticated
methodologies should help to answer many questions regarding
dietary antioxidants.
ar28
Br J Cancer Suppl 1987
Jun;8:153-7
Lipid antioxidants: how they may act in biological systems.
Niki E
Department of Reaction Chemistry, Faculty of Engineering,
University of Tokyo, Japan.
Chain breaking antioxidants scavenge the chain carrying oxygen
radicals and suppress the peroxidation of liposomal and
biological membranes in aqueous dispersions. Vitamin E scavenges
peroxyl radicals rapidly and its lateral diffusion is suggested
to be fast, but its antioxidant efficiency in the liposomal and
bio-membranes appears to be considerably smaller than in
homogeneous solution. Water soluble chain breaking antioxidants,
such as uric acid, cysteine, glutathione, and vitamin C,
scavenge radicals in the aqueous region and suppress the
peroxidation. However, they cannot scavenge the peroxyl radicals
within the lipid region of the membranes. Nevertheless, vitamin
C can interact with vitamin E radical, probably at
membrane-water interface, and regenerate vitamin E.
ar29
Oxidative injury in diseases of the central nervous system:
focus on alzheimer's disease.
Pratico D, Delanty N
Department of Pharmacology and Center for Experimental
Therapeutics, University of Pennsylvania, Philadelphia,
Pennsylvania, USA.
[Medline record in process]
Alzheimer's
disease is one of the most challenging brain disorders and has
profound medical and social consequences. It affects
approximately 15 million persons worldwide, and many more family
members and care givers are touched by the disease. The
initiating molecular event(s) is not known, and its
pathophysiology is highly complex. However, free radical injury
appears to be a fundamental process contributing to the neuronal
death seen in the disorder, and this hypothesis is supported by
many (although not all) studies using surrogate markers of
oxidative damage. In vitro and animal studies suggest that
various compounds with antioxidant ability can attenuate the
oxidative stress induced by beta-amyloid. Recently, clinical
trials have demonstrated potential benefits from treatment with
the antioxidants, vitamin E, selegiline, extract of Gingko
biloba, and idebenone. Further studies are warranted to confirm
these findings and explore the optimum timing and antioxidant
combination of such treatments in this therapeutically
frustrating disease.
PMID:
11063960, UI: 20519007
ar30
Compr Ther 1995;21(1):41-5
Levels of plasma lipid peroxide products and antioxidant
status in rheumatoid arthritis.
Kajanachumpol S, Vanichapuntu M, Verasertniyom O,
Totemchokchyakarn K, Vatanasuk M
Research Center, Faculty of Medicine, Ramathibodi Hospital,
Mahidol University, Bangkok, Thailand.
Oxygen free radicals have been implicated as mediators of tissue
damage in patients with rheumatoid arthritis.
ar31
Res Commun Mol Pathol Pharmacol 1997
Feb;95(2):179-89
Oxygen free radical scavenging abilities of vitamins C and E,
and a grape seed proanthocyanidin extract in vitro.
Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ
School of Pharmacy, Creighton University, Omaha, NE 68178, USA.
Proanthocyanidins, a group of polyphenolic bioflavonoids, have
been reported to
exhibit
a wide range of biological, pharmacological and chemoprotective
properties against oxygen free radicals. We have assessed the
concentration-dependent oxygen free radical scavenging abilities
of a grape seed proanthocyanidin extract (GSPE), vitamin C and
vitamin E succinate (VES) as well as superoxide dismutase,
catalase and mannitol against biochemically generated superoxide
anion and hydroxyl radical using a chemiluminescence assay and
cytochrome c reduction. A concentration-dependent inhibition was
demonstrated by GSPE. At a 100 mg/l concentration, GSPE
exhibited 78-81% inhibition of superoxide anion and hydroxyl
radical. Under similar conditions, vitamin C inhibited these two
oxygen free radicals by approximately 12-19%, while VES
inhibited the two radicals by 36-44%. The combination of
superoxide dismutase and catalase inhibited superoxide anion by
approximately 83%, while mannitol resulted in an 87% inhibition
of hydroxyl radical. The results demonstrate that GSPE is a more
potent scavenger of oxygen free radicals as compared to vitamin
C and VES.
PMID:
9090754, UI: 97246155
ar32
C R Acad Sci III 1998
Jan;321(1):31-8
High protection by grape seed proanthocyanidins (GSPC) of
polyunsaturated fatty acids against UV-C induced peroxidation.
Bouhamidi R, Prevost V, Nouvelot A
Laboratoire de neurosciences, UMR 6551 du CNRS, universite de
Caen, France.
The antioxidative effects of grape seed proanthocyanidins (GSPC)
were studied in three in-vitro models in which polyunsaturated
fatty acids (PUFAs) in aqueous solution and mice liver or brain
microsomes were used as oxidative substrates, and UV-C
irradiation as the pro-oxidant system. Analysis of UV-C induced
lipid peroxidation was carried out by two methods: gas liquid
chromatography of residual PUFAs and release of thiobarbituric
acid-reactive substances (TBARs) measured by TBA reaction.
Results indicate that PUFAs are more radiosensitive when
incorporated in single component micelles than in mixed
component micelles or microsomes. In every case, PUFA
peroxidation was inhibited by low concentrations of GSPC (2
mg/L) while epigallocatecin (EGC) and epigallocatechin gallate
(EGCG) monomers, at an equivalent level of epicatechin,
exhibited no efficacy in our experimental conditions. This
latter effect might be explained by a synergistic action of
flavan-3-ol monomers, dimers and oligomers contained in the
grape seed extract.
PMID:
9759355, UI: 98431519
ar33
Gen Pharmacol 1998
May;30(5):771-6
Protective effects of grape seed proanthocyanidins and
selected antioxidants against TPA-induced hepatic and brain
lipid peroxidation and DNA fragmentation, and peritoneal
macrophage activation in mice.
Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J,
Stohs SJ
Creighton University School of Pharmacy, Omaha, Nebraska, USA.
1. The comparative protective abilities of a grape seed
proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100
mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene
(50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
lipid peroxidation and DNA fragmentation in the hepatic and
brain tissues, as well as production of reactive oxygen species
by peritoneal macrophages, were assessed. 2. Treatment of mice
with GSPE (100 mg/kg), vitamin C, VES and beta-carotene
decreased TPA-induced production of reactive oxygen species, as
evidenced by decreases in the chemiluminescence response in
peritoneal macrophages by approximately 70%, 18%, 47% and 16%,
respectively, and cytochrome c reduction by approximately 65%,
15%, 37% and 19%, respectively, compared with controls. 3. GSPE,
vitamin C, VES and beta-carotene decreased TPA-induced DNA
fragmentation by approximately 47%, 10%, 30% and 11%,
respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%,
respectively, in the brain tissues, at the doses that were used.
Similar results were observed with respect to lipid peroxidation
in hepatic mitochondria and microsomes and in brain homogenates.
4. GSPE exhibited a dose-dependent inhibition of TPA-induced
lipid peroxidation and DNA fragmentation in liver and brain, as
well as a dose-dependent inhibition of TPA-induced reactive
oxygen species production in peritoneal macrophages. 5. GSPE and
other antioxidants provided significant protection against
TPA-induced oxidative damage, with GSPE providing better
protection than did other antioxidants at the doses that were
employed.
PMID:
9559333, UI: 98220087
ar34
Free Radic Res 1998
Oct;29(4):351-8
Antioxidant properties of catechins and proanthocyanidins:
effect of polymerisation, galloylation and glycosylation.
Plumb GW, De Pascual-Teresa S, Santos-Buelga C, Cheynier V,
ar34c
Williamson G
Biochemistry Department, Institute of Food Research, Norwich
Research Park, Colney, UK. geoff.plumb@bbsrc.ac.uk
A range of catechins and oligomeric procyanidins was purified by
high performance liquid chromatography (HPLC) from grape seed,
apple skin, lentil and almond flesh. Catechins, galloylated
epicatechin, glycosylated catechin, procyanidin dimers,
galloylated dimers, trimer, and tetramer species were all
identified, purified and quantified by HPLC, LC-MS and NMR. The
antioxidant properties of these compounds were assessed using
two methods: (a) inhibition of ascorbate/iron-induced
peroxidation of phosphatidylcholine liposomes; (b) scavenging of
the radical cation of
2,2'-azinobis(3-ethyl-benzothiazoline-6-sulphonate) (ABTS)
relative to the water-soluble vitamin E analogue Trolox C
(expressed as Trolox C equivalent antioxidant capacity, TEAC).
Antioxidant activity in the lipid phase decreased with
polymerisation in contrast with antioxidant action in the
aqueous phase which increased from monomer to trimer and then
decreased from trimer to tetramer. Galloylation of catechin and
dimeric procyanidins decreased lipid phase and increased aqueous
phase antioxidant activity. Glycosylation of catechin
demonstrated decreased activity in both phases.
PMID:
9860050, UI: 99075393
ar35
Am J Clin Nutr 2000
Feb;71(2 Part 2):621S-629S
Oxidative stress and Alzheimer disease(1).
Christen Y
Fondation Ipsen, Paris.
Research in the field of molecular biology has helped to provide
a better understanding of both the cascade of biochemical events
that occurs with Alzheimer disease (AD) and the heterogeneous
nature of the disease. One hypothesis that accounts for both the
heterogeneous nature of AD and the fact that aging is the most
obvious risk factor is that free radicals are involved. The
probability of this involvement is supported by the fact that
neurons are extremely sensitive to attacks by destructive free
radicals. Furthermore, lesions are present in the brains of AD
patients that are typically associated with attacks by free
radicals (eg, damage to DNA, protein oxidation, lipid
peroxidation, and advanced glycosylation end products), and
metals (eg, iron, copper, zinc, and aluminum) are present that
have catalytic activity that produce free radicals. beta-Amyloid
is aggregated and produces more free radicals in the presence of
free radicals; beta-amyloid toxicity is eliminated by free
radical scavengers. Apolipoprotein E is subject to attacks by
free radicals, and apolipoprotein E peroxidation has been
correlated with AD. In contrast, apolipoprotein E can act as a
free radical scavenger and this behavior is isoform dependent.
AD has been linked to mitochondrial anomalies affecting
cytochrome-c oxidase, and these anomalies may contribute to the
abnormal production of free radicals. Finally, many free radical
scavengers (eg, vitamin E, selegeline, and Ginkgo biloba extract
EGb 761) have produced promising results in relation to AD, as
has desferrioxamine-an iron-chelating agent-and antiinflammatory
drugs and estrogens, which also have an antioxidant effect.
ar36
Miner Electrolyte Metab 1991;17(2):124-32
Oxygen free radicals in acute renal failure.
Greene EL, Paller MS
University of Minnesota, Minneapolis.
Renal ischemia injures the renal tubular cell by disrupting the
vital cellular metabolic machinery. Further cell damage is
caused by restoration of blood flow when oxygen free radicals
are produced. Cellular sources of oxygen free radicals include
the electron transport chain, the microsomal electron transport
chain, oxidant enzymes (xanthine oxidase, cyclo-oxygenase),
phagocytes, and cellular auto-oxidation of Fe2+ and epinephrine.
Oxygen radicals cause lipid peroxidation of cell and organelle
membranes, disrupting the structural integrity and capacity for
cell transport and energy production. Studies in models of acute
renal failure have yielded convincing evidence that oxygen free
radical production occurs during ischemia/reperfusion. More than
a dozen reports have demonstrated the ability of exogenous
antioxidants to ameliorate renal injury in vivo. Direct
demonstration of increased oxygen free radical production during
reoxygenation following hypoxia has been shown in cultured renal
epithelial cells. Oxygen free radicals also play a role in toxic
acute renal failure. The therapeutic usefulness of free radical
scavengers remains to be tested.
ar37
Ren Fail 1999
Nov;21(6):627-34
Protective effect of a bioflavonoid proanthocyanidin-BP1 in
glycerol-induced acute renal failure in the rat: renal
stereological study.
Avramovic V, Vlahovic P, Mihailovic D, Stefanovic V
Institute of Histology and Embryology, Faculty of Medicine, Nis,
Yugoslavia.
Renal ischemia as well as oxygen metabolites play an important
role in renal injury during myoglobinuric acute renal failure
(ARF). On the other hand, flavonoids, a diverse group of
constituents naturally occurring in plants, have a strong
antioxidative activity, and have been implicated in vascular
relaxation. In this study the protective effect of a new
bioflavonoid proanthocyanidin-BP1 (BP1), extracted from seeds of
grapes, was evaluated in glycerol-induced ARF in rats.
Stereological methods were used to quantify changes in renal
morphology associated with ARF. Volume density of tubular lumen
and intratubular cast formations, nuclear parameters (area,
diameter, volume) of epithelial cells in the cortical proximal
tubules, and glomerular parameters (surface area, diameter,
volume, perimeter) were estimated on kidney sections of rats
treated either with 50% glycerol (8 mL/kg i.m.) alone. BP1 (20
mg/kg i.p.) in addition to glycerol, or BP1 alone. It was noted
that the volume density of tubular lumen and cast formations
were significantly lower (p < 0.001) in kidneys of the rats
treated with BP1 in addition to glycerol, compared with those
treated with glycerol alone. There were no significant
differences in glomerular and nuclear parameters between
glycerol treated, and BP1 in addition to glycerol treated rats.
Renal function was significantly improved in rats treated with
BP1 in addition to glycerol. The results suggest that BP1 is a
protective agent in glycerol model of ARF. This effect is
probably due to the antioxidative activity of BP1 and reduced
toxicity of myoglobin in renal tissue. Moreover, it is possible
that the ability of BP1 to protect the kidney is dependent upon
renal vascular relaxation. The potential beneficial effects of
bioflavonoid-BP1 demonstrated in experimental ARF could be
considered in therapy of myoglobinuric ARF.
PMID:
10586425, UI: 20052872
ar38
J Mol Cell Cardiol 1999
Jun;31(6):1289-97
Cardioprotective effects of grape seed proanthocyanidin
against ischemic reperfusion injury.
Sato M, Maulik G, Ray PS, Bagchi D, Das DK
University of Connecticut School of Medicine, Farmington,
Connecticut 06030-1110, USA.
There is increasing evidence to indicate cardioprotective
effects of red wine consumption. Such cardioprotective
properties of wine have been attributed to certain polyphenolic
constituents of grapes. The purpose of this investigation was to
examine whether proanthocyanidins derived from grape seeds
possess cardioprotective properties. Rats were randomly divided
into two groups: grape-seed proanthocyanidin was administered
orally to one group of rats (100 mg/kg/day) for 3 weeks while
the other group served as control. After 3 weeks, rats were
killed, hearts excised, mounted on the perfusion apparatus and
perfused with Krebs-Henseleit bicarbonate (KHB) buffer. After
stabilization hearts were perfused in the working mode for
baseline measurements of contractile functions. Hearts were then
subjected to 30 min of global ischemia followed by 2 h of
reperfusion. Coronary perfusates were collected to monitor
malonaldehyde formation, a presumptive marker for oxidative
stress development. At the end of each experiment, the heart was
processed for infarct size determination. Peroxyl radical
scavenging activity of proanthocyanidin was determined by
examining its ability to remove peroxyl radical generated by
2,2'-azobis (2-amidinopropane) dihydrochloride while hydroxyl
radical scavenging activity was tested with its ability to
reduce 7-OH.-coumarin-3-carboxylic acid. The results of our
study demonstrated that proanthocyanidin-fed animals were
resistant to myocardial ischemia reperfusion injury as evidenced
by improved recovery of post-ischemic contractile functions. The
proanthocyanidin-fed group revealed reduced extent of myocardial
infarction compared to the control group. Fluorimetric study
demonstrated the antioxidant property of proanthocyanidin as
judged by its ability to directly scavenge peroxyl radicals.
Taken together, the results of this study showed that grape
seed-proanthocyanidins possess a cardioprotective effect against
ischemia reperfusion injury. Such cardioprotective property, at
least in part, may be attributed to its ability to directly
scavenge peroxyl and hydroxyl radicals and to reduce oxidative
stress developed during ischemia and reperfusion. Copyright 1999
Academic Press.
PMID:
10371703, UI: 99301913
ar39
Conn Med 1995
Oct;59(10):579-88
(gsx7) Free radicals, oxidative stress, oxidized low density
lipoprotein (LDL), and the heart: antioxidants and other ar39c
strategies to limit cardiovascular damage.
Sinatra ST, DeMarco J
Manchester Memorial Hospital, USA.
The heart is the most susceptible of all the organs to premature
aging and free radical oxidative stress. Clinical research has
clearly documented the role of free radical damage and the
progression of numerous degenerative diseases, particularly
cardiovascular disease. This may be the result of acute
ischemia-reperfusion injury, endothelial damage of
hyperhomocysteinemia, as well as chronic oxidative damage
secondary to lipid peroxidation. Fortunately, although highly
responsive, and therefore vulnerable to the effects of oxidative
stress, the heart is also receptive to the benefits of targeted
phytonutrients, antioxidants, and nutritionals. The effects of
antioxidant nutrients have been extensively evaluated in
epidemiological, population, and clinical studies.
Phytonutrients such as the natural flavonoids and carotenoids
found in fresh fruits and vegetables or vitamins C, E, and
beta-carotene have powerful antioxidant effects. In addition,
minerals like selenium and nutrients such as coenzyme Q10 will
minimize free radical risk and optimize a favorable outcome from
the ubiquitous presence of oxidative stress on the
cardiovascular system. The B complex, particularly folic acid,
B12, and B6 are also essential in the prevention of
hyperhomocysteinemia, another major risk factor for the
circulatory system. Measures to minimize accumulation of heavy
metals in the body, especially iron and copper, which are
capable of initiating adverse free radical reactions, will also
help to assuage oxidative stress. Thus, the combination of a
healthy diet supplemented with antioxidants and phytonutrients
may be useful in the prevention and promotion of optimum
cardiovascular health.
ar40
Ann Thorac Surg 1989
Jun;47(6):939-45
Free radicals and myocardial protection: a surgical viewpoint.
Menasche P, Piwnica A
Department of Cardiovascular Surgery, Hopital Lariboisiere,
Paris, France.
Oxygen-derived free radicals are now considered important
contributors to tissue injury associated with ischemia and
reperfusion. Transition metals, primarily iron, greatly enhance
the generation of these active species, which can destroy a
large variety of biomolecules, in particular the lipid
components of cell membranes. This review tries to demonstrate
why cardiopulmonary bypass and aortic cross-clamping are
situations that predispose to oxygen free radical production,
and how "anti-free radical" agents such as enzymatic scavengers,
antioxidants, and iron chelators may prove to be useful
therapeutic adjuncts in the clinical setting of open heart
surgery.
ar41
Free Radic Biol Med 1988;4(1):15-24
Evidence of direct toxic effects of free radicals on the
myocardium.
Burton KP
Department of Physiology, University of Texas Health Science
Center, Dallas 75235.
The hypothesis that oxygen-derived free radicals do indeed play
a role in myocardial ischemic and reperfusion injury has
received a lot of support. Experimental results have shown that
free radical scavengers can protect against certain aspects of
myocardial ischemic injury and that on reperfusion the heart
approaches a level that is more normal than those hearts not
receiving additional scavenging agents.
ar42
Basic Res Cardiol 1982
Sep-Oct;77(5):465-85
The role of lipid peroxidation in pathogenesis of ischemic
damage and the antioxidant protection of the heart.
Meerson FZ, Kagan VE, Kozlov YuP, Belkina LM, Arkhipenko YuV
A working hypothesis on pathogenesis of ischemic heart damage
has been proposed. According to this hypothesis, a crucial role
in conversion of reversible damage into irreversible damage is
played by cardiomyocyte membrane destruction caused by the
so-called "lipid triad". The latter comprises activation of
lipid peroxidation, activation of phospholipases, and the
detergentlike action of excessive amounts of free fatty acids
and lysophospholipids. Marked activation of lipid peroxidation
in experimental myocardial infarction, as well as reoxygenation
following transitory ischemia, have been demonstrated. The
proposed hypothesis and experimental data underly successful
application of synthetic free radical scavengers (antioxidants)
for heart protection against experimental myocardial infarction,
transitory ischemia, and emotional, painful stress.
PMID:
7181828, UI: 83100260
ar43
J Mol Cell Cardiol 1999
Jun;31(6):1289-97
Cardioprotective effects of grape seed proanthocyanidin
against ischemic reperfusion injury.
Sato M, Maulik G, Ray PS, Bagchi D, Das DK
University of Connecticut School of Medicine, Farmington,
Connecticut 06030-1110, USA.
There is increasing evidence to indicate cardioprotective
effects of red wine consumption. Such cardioprotective
properties of wine have been attributed to certain polyphenolic
constituents of grapes. The purpose of this investigation was to
examine whether proanthocyanidins derived from grape seeds
possess cardioprotective properties. Rats were randomly divided
into two groups: grape-seed proanthocyanidin was administered
orally to one group of rats (100 mg/kg/day) for 3 weeks while
the other group served as control. After 3 weeks, rats were
killed, hearts excised, mounted on the perfusion apparatus and
perfused with Krebs-Henseleit bicarbonate (KHB) buffer. After
stabilization hearts were perfused in the working mode for
baseline measurements of contractile functions. Hearts were then
subjected to 30 min of global ischemia followed by 2 h of
reperfusion. Coronary perfusates were collected to monitor
malonaldehyde formation, a presumptive marker for oxidative
stress development. At the end of each experiment, the heart was
processed for infarct
size
determination. Peroxyl radical scavenging activity of
proanthocyanidin was determined by examining its ability to
remove peroxyl radical generated by 2,2'-azobis
(2-amidinopropane) dihydrochloride while hydroxyl radical
scavenging activity was tested with its ability to reduce
7-OH.-coumarin-3-carboxylic acid. The results of our study
demonstrated that proanthocyanidin-fed animals were resistant to
myocardial ischemia reperfusion injury as evidenced by improved
recovery of post-ischemic contractile functions. The
proanthocyanidin-fed group revealed reduced extent of myocardial
infarction compared to the control group. Fluorimetric study
demonstrated the antioxidant property of proanthocyanidin as
judged by its ability to directly scavenge peroxyl radicals.
Taken together, the results of this study showed that grape
seed-proanthocyanidins possess a cardioprotective effect against
ischemia reperfusion injury. Such cardioprotective property, at
least in part, may be attributed to its ability to directly
scavenge peroxyl and hydroxyl radicals and to reduce oxidative
stress developed during ischemia and reperfusion. Copyright 1999
Academic Press.
PMID:
10371703, UI: 99301913
ar44
Nutr Metab Cardiovasc Dis 2000
Feb;10(1):38-44
Dietary antioxidants for cardiovascular prevention.
Giugliano D
Dipartimento di Gerontologia, Geriatria e Malattie del
Metabolismo, Seconda Universita di Napoli, Italy.
The generation of reactive oxygen species (ROS) is associated
with life in aerobic conditions. ROS are thought to be
implicated in the pathogenesis of various human diseases since
they are capable of damaging biological macromolecules such as
DNA, carbohydrates and proteins. The organism maintains defense
against ROS, including enzymes and low molecular-weight
antioxidants. An important source of antioxidants is diet which
contains numerous compounds exhibiting antioxidant activity. A
shortage of antioxidants in the diet might promote coronary
heart disease through accumulation of oxidized LDL in
macrophages. However, antioxidants may also influence
endothelial functions, smooth muscle cell proliferation,
thrombosis and plaque rupture.
ar45
Drugs Exp Clin Res 1999;25(2-3):115-20
Cardioprotection of red wine: role of polyphenolic
antioxidants.
Das DK, Sato M, Ray PS, Maulik G, Engelman RM, Bertelli AA,
Bertelli A
University of Connecticut School of Medicine, Farmington, CT
06030-1110, USA.
Epidemiological studies suggest that the consumption of wine,
particularly of red wine, reduces the incidence of mortality and
morbidity from coronary heart disease. This has given rise to
what is now popularly termed the "French paradox". The
cardioprotective effect has been attributed to antioxidants
present in the polyphenol fraction of red wine. Grapes contain a
variety of antioxidants, including resveratrol, catechin,
epicatechin and proanthocyanidins. Of these, resveratrol is
present mainly in grape skin while proanthocyanidin is present
in the seeds. In this report, we provide evidence that red wine
extract as well as resveratrol and proanthocyanidins are equally
effective in reducing myocardial ischemic reperfusion injury,
which suggests that these red wine polyphenolic antioxidants
play a crucial role in cardioprotection.
PMID:
10370873, UI: 99299011
ar46
J Cardiovasc Pharmacol 1995 Jul;26(1):90-5
"Endothelium-dependent vasorelaxation caused by various plant
extracts."
Fitzpatrick DF, Hirschfield SL, Ricci T, Jantzen P, Coffey
RG
In a previous study (Am J Physiol 1993;265: H774-8), we
found that certain red wines and other grape products caused
endothelium-dependent vasorelaxation. In the present study,
aqueous extracts of a variety of vegetables, fruits, teas, nuts,
herbs, and spices were tested for their endothelium-dependent
relaxing ability in vitro. Rings of rat aorta, with or without
an intact endothelium, were mounted in tissue baths, contracted
with phenylephrine, and then exposed to diluted plant extracts.
Many, but not all, extracts exhibited endothelium-dependent
relaxations that were reversed by NG-monomethyl-L-arginine, a
nitric oxide synthase inhibitor, which suggested involvement of
nitric oxide, the endothelium-derived relaxing factor in the
response. Furthermore, extracts that caused relaxation also
increased tissue levels of cyclic GMP, the mediator of nitric
oxide-induced vascular smooth-muscle relaxation. These results
may lend further support to mounting evidence that plant foods
contain compounds that, if absorbed intact and in sufficient
quantities, could conceivably be beneficial in prevention of
cardiovascular disease.
ar47
Orv Hetil 1997
Sep 7;138(36 Suppl 2):2283-7
The role of oxidative stress and the preventive effect of free
radical scavengers in arteriosclerosis
Feher J, Blazovics A, Somogyi A, Lengyel G
Semmelweis Orvostudomanyi Egyetem II. Belgyogyaszati Klinika,
Budapest.
The role of oxidative stress in the development of
arteriosclerosis is well established. This pathogenetic
explanation unificates in itself the lipid and thrombotic
theories. The authors summarize the most substantial literary
data in this relation, they discuss in details those therapic
methods, in which the natural and synthetic antioxidants are
involved as preventive drugs in the development and consequences
of arteriosclerosis. Thus the effects of the dihydroquinoline
type antioxidants as well as those of Vitamins A, C and E are
discussed partly in experimental, partly in clinical studies.
The authors conclude on the basis of own and literary data that
the application of antioxidants could decrease the blood vessel
alterations produced by arteriosclerosis, as well as the
pathological tissue alterations developed in the consequences of
ischaemia.
ar48
Atherosclerosis 1999
Jan;142(1):139-49
Proanthocyanidin-rich extract from grape seeds attenuates the
development of aortic atherosclerosis in cholesterol-fed
rabbits.
Yamakoshi J, Kataoka S, Koga T, Ariga T
Research and Development Division, Kikkoman Corporation, Noda
City, Chiba Pref, Japan.
The aim of this study was to evaluate the antiatherosclerotic
effect of proanthocyanidin-rich extracts from grape seeds in
cholesterol-fed rabbits. Proanthocyanidin-rich extracts (0.1%
and 1% in diets [w/w]) did not appreciably affect the changes in
serum lipid profile of cholesterol-fed rabbits. The level of
cholesteryl ester hydroperoxides (ChE-OOH) induced by
2,2'-azobis(2-amidinopropane-dihydrochloride (AAPH) were lower
in the plasma of rabbits fed proanthocyanidin-rich extract plus
cholesterol than in the plasma of rabbits fed cholesterol alone,
but not in the low-density lipoprotein (LDL). Aortic
malondialdehyde (MDA) content decreased in rabbits fed
proanthocyanidin-rich extract. Feeding proanthocyanidin-rich
extracts (0.1 and 1% in the diet) to rabbits significantly
reduced severe atherosclerosis in the aorta. Immunohistochemical
analysis revealed a decrease in the number of oxidized
LDL-positive macrophage-derived foam cells in atherosclerotic
lesions in the aorta of rabbits fed proanthocyanidin-rich
extract. When proanthocyanidin-rich extract was administered
orally to rats, proanthocyanidin was detected in the plasma by
Porters method but not in the lipoproteins (LDL plus VLDL). In
an in vitro experiment using human plasma, proanthocyanidin-rich
extract added to the plasma inhibited the oxidation of
cholesteryl linoleate in LDL, but not in the LDL isolated after
the plasma and the extract were incubated in advance. These
results suggested that proanthocyanidins, the major polyphenols
in red wine, might trap reactive oxygen species in aqueous
series such as plasma and interstitial fluid of the arterial
wall, thereby inhibiting oxidation of LDL and showing an
antiatherosclerotic activity.
Comments:
*Comment
in: Atherosclerosis 1999 Aug;145(2):421-2PMID: 9920515, UI:
99117243
ar49
Minerva Cardioangiol 1999
Jan-Feb;47(1-2):39-46
Clinical and capillaroscopic evaluation of chronic
uncomplicated venous insufficiency with procyanidins extracted
from vitis vinifera
Costantini A, De Bernardi T, Gotti A
Istituto di Chirurgia Vascolare e Angiologia, Universita degli
Studi, Milano.
Minerva
Cardioangiol 1999 Jan-Feb;47(1-2):39-46
[Clinical
and capillaroscopic evaluation of chronic uncomplicated venous
insufficiency with procyanidins extracted from vitis
vinifera].Costantini A, De Bernardi T, Gotti A Istituto di
Chirurgia Vascolare e Angiologia, Universita degli Studi,
Milano. BACKGROUND: The pharmacological treatment of
non-complicated chronic venous insufficiency is a current and
well-debated topic. The introduction of new products with action
on the venous system, improved knowledge on the physiopathology
of venous insufficiency and the possibility provided by new
analytical instruments, have given new impulse to the
consolidation of the clinical value of phlebotonics in this
indication. METHODS: In light of this, 24 patients with
non-complicated chronic venous insufficiency were treated with
oral administration of Oligomeric Proanthocyanidins
(Pycnogenols-OPC) 100 mg/day. To evaluate the therapeutic
efficacy of the treatment, an instrumental evaluation by optical
probe capillaroscope was employed in addition to the traditional
subjective clinical parameters: swelling, itching, heaviness and
pain.
The
videocapillaroscope examination was performed at the lower third
of the leg and the first toe. Edema in the capillaroscopic
field, the number of observable capillaries and the capillary
dilatation were the parameter chosen to evaluate the efficacy of
treatment. All patients completed the study with no reports of
adverse events during the period of observation. RESULTS: The
results obtained show a positive clinical response (improved or
absent symptoms) in over 80% of patients, with significant
improvement of symptoms already evident after the first 10 days
of treatment. The mechanism of action of the OPCs explains the
rapid reduction of the swelling of the lower limbs and
correlated with this are the other evaluable symptoms: heaviness
and itching. Particularly striking results were observed for
itching and pain which completely disappeared during the course
of therapy in 80% and 53% of the patients respectively.
Noteworthy is the good correlation between the clinical and
instrumental data, with improvement in a total of 70% of
patients. CONCLUSIONS: The results obtained in the course of
this clinical experience, with evident improvement already
during the first weeks of treatment, the absence of adverse
events added to the benefit of a once-a-day administration,
justify the use of OPC in the treatment of non-complicated
chronic venous insufficiency. PMID: 10356940, UI: 99285428
ar50
Free Radic Biol Med 1996;21(4):505-11
Effect of vitamin E on human aortic endothelial cell responses
to oxidative injury.
Martin A, Wu D, Baur W, Meydani SN, Blumberg JB, Meydani M
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts
University, Boston, MA 02111, USA.
Reactive oxygen species produced by the cells present in the
arterial wall may cause oxidative damage to cellular components
altering endothelial cell (EC) function. Changes in the EC
function appear to play a key role in the pathogenesis of
atherosclerosis. Human aortic endothelial cells (HAEC) were
employed to investigate the protective role of vitamin E upon
exposure of endothelial cells to oxidative stress in vitro. HAEC
assimilate d-alpha-tocopherol from the media in a dose-dependent
manner. Exposure of HAEC to 16.5 mM of the free radical
generator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH)
for 16 h decreased cell viability (assessed by trypan blue
exclusion) from 90 to 28%. HAEC preincubated with vitamin E at
15, 30, and 60 microM prior to the AAPH exposure resulted in a
dose-dependent increase in resistance to oxidative stress and
increased cell viability by 37, 66, and 85%, respectively. An
increase in prostacyclin (PGI2) production by HAEC in response
to AAPH exposure was correlated positively with cell damage and
negatively with vitamin E concentration. Interleukin (IL)-1
production also increased in parallel with cell damage induced
by AAPH. Vitamin E treatment significantly reduced IL-1
production after AAPH exposure. This modulatory role of vitamin
E on HAEC function following exposure to an oxidative stress may
reflect its antioxidant protection against lipid peroxidation.
PMID:
8886801, UI: 97041530
ar51
Ann Med 1994
Dec;26(6):435-41
Antioxidants and carcinogenesis.
Rautalahti M, Huttunen J
Cancer Prevention Unit, National Public Health Institute,
Helsinki, Finland.
It
is established beyond doubt that free radicals in tissues and
cells can damage DNA, proteins, carbohydrates and lipids. These
potentially deleterious reactions are at least partly controlled
by antioxidants capable of scavenging free radicals. It is
widely believed that a proper balance between free radicals and
antioxidants is essential for the health of an organism. A vast
body of observational epidemiological studies has suggested that
high intake of dietary or supplemental antioxidants protects
against ischaemic heart disease, various types of cancer and
several other diseases.
ar52
Compr Ther 1995;21(1):41-5
Antioxidants protection against cancer and other human
diseases.
Uddin S, Ahmad S
Department of Medicine, Stritch School of Medicine, Loyola
University of Chicago, Maywood, Illinois, USA.
Antioxidants are of primary value biologically by restricting
the damage that reactive free radicals can do to the cell and
the cellular components. Antioxidants may afford varying degrees
of protection against the cell damage caused by these reactive
oxygen free radicals. The antioxidant(s) is/are much more likely
to be effective against chemical carcinogens that are
metabolically activated to the
reactive
free-radical intermediates that are self-propagating than in
situations where the metabolic activation results in nonradical
reactive intermediates, such as epoxides or carbonium ions.
Free-radical disturbances may be of primary and major
significance in some important human diseases and intoxication,
administration and/or intake may turn out to be of substantial
value in the treatment of such cases.
ar53
Free-radical processes in multistage carcinogenesis.
Borek C
Department of Radiation Oncology, Columbia University New York,
N.Y. 10032.
Rodent and human cells in culture, transformed in vitro by
radiation or chemicals into malignant cells, afford us the
opportunity to probe into early and late events in the
neoplastic process at a cellular and molecular level.
Transformation can be regarded as an abnormal expression of
cellular genes. The initiating agents disrupt the integrity of
the genetic apparatus altering DNA in ways that result in the
activation of cellular transforming genes (oncogenes) during
some stage of the neoplastic process. Events associated with
initiation and promotion may overlap to some degree, but in
order for them to occur, cellular permissive conditions prevail.
Permissive and potentiating factors include free radicals, and
thyroid hormone, and inadequate antioxidants. Protective factors
which suppress the carcinogenic process include enzymatic and
dietary antioxidants. These are constitutive under normal
circumstances and can be induced under conditions of oxidative
stress produced by a wide range of carcinogens.
ar54
Mol Cell Biochem 1999
Jun;196(1-2):99-108
The cytotoxic effects of a novel IH636 grape seed
proanthocyanidin extract on cultured human cancer cells.
Ye X, Krohn RL, Liu W, Joshi SS, Kuszynski CA, McGinn TR,
Bagchi M, Preuss HG, Stohs SJ, Bagchi D
Creighton University School of Pharmacy and Allied Health
Professions, Omaha, NE 68178, USA.
Grape seed proanthocyanidins are natural antioxidants which
possess a broad spectrum of chemoprotective properties against
free radicals and oxidative stress. In this study, we have
assessed the cytotoxicity of a novel IH636 grape seed
proanthocyanidin extract (GSPE) against MCF-7 human breast
cancer cells, A-427 human lung cancer cells, CRL-1739 human
gastric adenocarcinoma cells and K562 chronic myelogenous
leukemic cells at 25 and 50 mg/lit concentrations for 0-72 h
using cytomorphology and MTT cytotoxicity assay. In addition, we
compared the effects on normal human gastric mucosal cells and
normal J774A.1 murine macrophage cells with the effects on the
cancer cell lines. Concentration- and time-dependent cytotoxic
effects of GSPE were observed on the MCF-7 breast cancer, A-427
lung cancer and gastric adenocarcinoma cells. Following
incubation of the MCF-7 cells with 25 mg/lit of the GSPE
approximately 6.5, 30 and 43% inhibitions in cell growth were
observed at 24, 48 and 72 h of incubation, respectively, while
incubation of the MCF-7 cells with 50 mg/lit of the GSPE
resulted in 11, 35 and 47% inhibition in cell growth at these
same points, respectively. Similar results were observed in the
A-427 and gastric adenocarcinoma cells. GSPE exhibited no
cytotoxicity toward the neoplastic K562 myelogenous leukemic
cells. However, GSPE enhanced the growth and viability of the
normal human gastric mucosal cells and J774A.1 murine macrophage
cells. These data demonstrate that GSPE exhibited cytotoxicity
towards some cancer cells, while enhancing the growth and
viability of the normal cells which were examined.
PMID:
10448908, UI: 99376138
ar55
Anticarcinogenic Effect of a Polyphenolic Fraction Isolated
From Grape Seeds in Human Prostate Carcinoma DU145 Cells:
Modulation of Mitogenic Signaling and Cell-Cycle Regulators
and Induction of G1 Arrest and Apoptosis
Chapla Agarwal 1 *, Yogesh Sharma 1, Rajesh Agarwal 1 2
1Center for Cancer Causation and Prevention, AMC Cancer Research
Center, Denver, Colorado
2University of Colorado Cancer Center, University of Colorado
Health Sciences Center, Denver, Colorado
*Correspondence to Chapla Agarwal, Center for Cancer Causation
and Prevention, AMC Cancer Research Center, 1600 Pierce Street,
Denver, CO 80214.
(gsx4)
Abstract
There
is an increasing interest in identifying potent cancer
preventive and therapeutic agents against prostate cancer (PCA).
In a recent study, we showed that a polyphenolic fraction
isolated from grape seeds (hereafter referred to as GSP) that is
substantially rich in antioxidant procyanidins exerts
exceptionally high preventive effects against tumorigenesis in a
murine skin model. In the present study, we investigated the
anticarcinogenic effect of GSP against PCA by employing DU145
human prostate carcinoma cells. GSP treatment (10-100 g/mL
doses for 2-6 d) of cells resulted in a highly significant
(P < 0.01-0.001) inhibition of cell growth in both
dose- and time-dependent manner. Compared with the vehicle,
2 d of GSP treatment resulted in 27, 39, and 76% growth
inhibition at 50, 75, and 100 g/mL doses, respectively,
whereas 28-97% and ar55c
12-98%
inhibition was evident at 10-100 g/mL doses of GSP after 4
and 6 d of treatment, respectively. These doses of GSP also
resulted in dose- and time-dependent cell death (6-50%,
P <0.1-0.001) that was later characterized as apoptotic
death. In molecular mechanistic studies, treatment of DU145
cells with GSP at 25-75 g/mL doses for 24, 48, and
72 h resulted in 77-88%, 65-93%, and 38-98% reduction,
respectively (P < 0.001), in phospho-extracellular
signal-regulated protein kinase (ERK) 1 and 78%, 19-76%, and
63-71% reduction (P < 0.1-0.001) in phospho-ERK2
levels, respectively. In other studies, similar doses of GSP
showed up to 1.9-fold increases in Cip1/p21 and a significant
(P < 0.001) decrease in cyclin-dependent kinase
(CDK) 4 (up to 90% decrease), CDK2 (up to 50% decrease), and
cyclin E (up to 60%decrease). GSP treatment of DU145 cells also
resulted in a significant (P < 0.001) G1 arrest in
cell-cycle progression in a dose-dependent manner. The
growth-inhibitory and cell-death effects of GSP were also
observed in another human PCA line, LNCaP. Together, these
results suggest that GSP may exert strong anticarcinogenic
effect against PCA and that this effect possibly involves
modulation of mitogenic signaling and cell-cycle regulators and
induction of G1 arrest, cell-growth inhibition, and apoptotic
death. Mol. Carcinog. 28:129-138, 2000. © 2000 Wiley-Liss, Inc.
ar56
Potent inhibitory action of red wine polyphenols on human
breast cancer cells
Athina Damianaki, Efstathia Bakogeorgou, Marilenna Kampa,
Anastassia Hatzoglou, Claudia Gemetzi, Elias Castanas
Laboratory of Experimental Endocrinology, University of Crete,
School of Medicine and University Hospital, Heraklion GR-71110,
Greece
George Notas, Elias Kouroumalis
Laboratory of Gastroenterology, University of Crete, School of
Medicine and University Hospital, Heraklion GR-71110, Greece
Simone Panagiotou, Pierre-Marie Martin
Laboratory of Experimental Cancerology, University of Marseille,
F-13916, France
Abstract:
Breast cancer (one of the most common malignancy in Western
societies), as well as esophagus, stomach, lung, bladder, and
prostate cancer, depend on environmental factors and diet for
growth and evolution. Dietary micronutriments have been proposed
as effective inhibitory agents for cancer initiation,
progression, and incidence. Among them, polyphenols, present in
different foods and beverages, have retained attention in recent
years. Red wine is a rich source of polyphenols, and their
antioxidant and tumor arresting effects have been demonstrated
in different in vitro and in vivo systems. In the present study,
we have measured the antiproliferative effect of red wine
concentrate, its total polyphenolic pool, and purified catechin,
epicatechin, quercetin, and resveratrol, which account for more
than 70% of the total polyphenols in red wine, on the
proliferation of hormone sensitive (MCF7, T47D) and resistant
(MDA-MB-231) breast cancer cell lines. Our results indicate that
polyphenols, at the picomolar or the nanomolar range, decrease
cell proliferation in a dose- and a time-dependant manner. In
hormone sensitive cell lines, a specific interaction of each
polyphenol with steroid receptors was observed, with IC50s lower
than previously described. Interaction of polyphenols with
steroid receptors cannot fully explain their inhibitory effect
on cell proliferation. In addition, discrete antioxidant action
on each cell line was detected under the same concentrations,
both by modifying the toxic effect of H2O2, and the production
of reactive oxygen species (ROS), after phorbol ester
stimulation. Our results suggest that low concentrations of
polyphenols, and consecutively, consumption of wine, or other
polyphenol-rich foods and beverages, could have a beneficial
antiproliferative effect on breast cancer cell growth. J. Cell.
Biochem. 78:429-441, 2000. © 2000 Wiley-Liss, Inc.
ar57
Anticancer Res 1995
Jul-Aug;15(4):1183-9
Ability of m-chloroperoxybenzoic acid to induce the ornithine
decarboxylase marker of skin tumor promotion and inhibition of
this response by gallotannins, oligomeric proanthocyanidins,
and their monomeric units in mouse epidermis in vivo.
Chen G, Perchellet EM, Gao XM, Newell SW, Hemingway RW,
Bottari V, Perchellet JP
Anti-Cancer Drug Laboratory, Kansas State University, Manhattan
66506-4901, USA.
m-Chloroperoxybenzoic acid (CPBA) was tested for its ability to
induce the ornithine decarboxylase (ODC) marker of skin tumor
promotion. In contrast to benzoyl peroxide, dicumyl peroxide,
and 2-butanol peroxide, 5 mg of CPBA applied twice at a 72-h
interval induce ODC activity at least as much as 3 micrograms of
12-O-tetradecanoylphorbol-13-acetate (TPA). ODC induction peaks
36 h after a single CPBA treatment but is maximal 5 h after two
applications of CPBA at a 48-h interval. The ODC-inducing
activity of CPBA is dose dependent and sustained after chronic
treatment. In contrast to TPA, two CPBA treatments at 12-24 h
intervals produce no refractory state against ODC induction. The
mechanism of ODC induction by CPBA is iron dependent. Various
hydrolyzable tannins, condensed tannins (CTs) and their
monomeric units remarkably inhibit the ODC response to multiple
CPBA treatments. At 12 mg, gallic acid, Aleppo gall tannic acid
(TA), catechin, and loblolly pine bark CT inhibit the most
CPBA-induced ODC activity. Aleppo gall TA is even effective when
applied several hours before CPBA. The tumor-promoting activity
of CPBA and its inhibition by plant tannins remain to be
evaluated.
PMID:
7653998, UI: 95382557
ar58
Cancer Lett 1999
Jan 29;135(2):151-7
Inhibition of TPA-induced tumor promotion in CD-1 mouse
epidermis by a polyphenolic fraction from grape seeds.
Bomser JA, Singletary KW, Wallig MA, Smith MA
Department of Food Science and Human Nutrition, University of
Illinois, Urbana 61801, USA.The anti-tumor promoting activity of
a polyphenolic fraction from grape seeds (GSP) was examined in
CD-1 mouse skin epidermis. Specifically, the ability of this
fraction to inhibit 12-O-tetradecanoylphorbol-13-acetate
(TPA)-induced tumor promotion and two markers of promotion in
mouse skin, ornithine decarboxylase (ODC) and myeloperoxidase
(MPO) activities, was evaluated. Pretreatment of mouse skin with
5, 10, 20 and 30 mg of GSP resulted in a dose-dependent
reduction in TPA-induced epidermal ODC activity of 27, 37, 48
and 70%, respectively, compared to controls. In addition,
pretreatment of mouse skin with 1, 5, 10 and 20 mg of GSP
resulted in a significant 43, 39, 54 and 73% inhibition of MPO
activity, respectively, compared to controls. In
7,12-dimethylbenz[a]anthracene (DMBA)-initiated CD-1 mice,
biweekly treatment of mouse skin with 5, 10, and 20 mg of GSP 20
min prior to TPA application resulted in a 30, 40, and 60%
inhibition of final skin tumor incidence, respectively, compared
to controls. In addition, the final number of tumors per mouse
in the 5, 10 and 20 mg GSP-treated animals was decreased 63, 51,
and 94%, respectively, compared to controls. These studies
indicate that GSP possesses anti-tumor promoting activity when
applied to CD-1 mouse skin prior to treatment with TPA. The
mechanism of this tumor inhibition is due, in part, to a
GSP-associated inhibition of TPA-induced epidermal ODC and MPO
activities. Thus, GSP warrants further evaluation as a skin
cancer chemopreventative agent.
PMID:
10096423, UI: 99194087
ar59
Molecular Carcinogenesis
Volume 28, Issue 3, 2000. Pages: 129-138
Anticarcinogenic Effect of a Polyphenolic Fraction Isolated
From Grape Seeds in Human Prostate Carcinoma DU145 Cells:
Modulation of Mitogenic Signaling and Cell-Cycle Regulators
and Induction of G1 Arrest and Apoptosis
Chapla Agarwal 1 *, Yogesh Sharma 1, Rajesh Agarwal 1 2
1Center for Cancer Causation and Prevention, AMC Cancer Research
Center, Denver, Colorado
2University of Colorado Cancer Center, University of Colorado
Health Sciences Center, Denver, Colorado
There is an increasing interest in identifying potent cancer
preventive and therapeutic agents against prostate cancer (PCA).
In a recent study, we showed that a polyphenolic fraction
isolated from grape seeds (hereafter referred to as GSP) that is
substantially rich in antioxidant procyanidins exerts
exceptionally high preventive effects against tumorigenesis in a
murine skin model. In the present study, we investigated the
anticarcinogenic effect of GSP against PCA by employing DU145
human prostate carcinoma cells. GSP treatment (10-100 g/mL
doses for 2-6 d) of cells resulted in a highly significant
(P < 0.01-0.001) inhibition of cell growth in both
dose- and time-dependent manner. Compared with the vehicle,
2 d of GSP treatment resulted in 27, 39, and 76% growth
inhibition at 50, 75, and 100 g/mL doses, respectively,
whereas 28-97% and 12-98% inhibition was evident at
10-100 g/mL doses of GSP after 4 and 6 d of treatment,
respectively. These doses of GSP also resulted in dose- and
time-dependent cell death (6-50%, P <0.1-0.001) that was
later characterized as apoptotic death. In molecular mechanistic
studies, treatment of DU145 cells with GSP at 25-75 g/mL
doses for 24, 48, and 72 h resulted in 77-88%, 65-93%, and
38-98% reduction, respectively (P < 0.001), in
phospho-extracellular signal-regulated protein kinase (ERK) 1
and 78%, 19-76%, and 63-71% reduction
(P < 0.1-0.001) in phospho-ERK2 levels,
respectively. In other studies, similar doses of GSP showed up
to 1.9-fold increases in Cip1/p21 and a significant
(P < 0.001) decrease in cyclin-dependent kinase
(CDK) 4 (up to 90% decrease), CDK2 (up to 50% decrease), and
cyclin E (up to 60% decrease). GSP treatment of DU145 cells also
resulted in a significant (P < 0.001) G1 arrest in
cell-cycle progression in a dose-dependent manner. The
growth-inhibitory and cell-death effects of GSP were also
observed in another human PCA line, LNCaP. Together, these
results suggest that GSP may exert strong anticarcinogenic
effect against PCA and that this effect possibly involves
modulation of mitogenic signaling and cell-cycle regulators and
induction of G1 arrest, cell-growth inhibition, and apoptotic
death. Mol. Carcinog. 28:129-138, 2000. © 2000 Wiley-Liss, Inc.
ar60
Phytotherapy Research
Volume 12, Issue 8, 1998. Pages:
568-571
Hydrogen peroxide-induced modulation of intracellular
oxidized states in cultured macrophage J774A.1 and neuroactive
PC-12 cells, and protection by a novel grape seed
proanthocyanidin extract
D. Bagchi 1, C. Kuszynski 2, J. Balmoori 1, M. Bagchi 1, S. J.
Stohs 1 *
1Departments of Pharmaceutical and Administrative Sciences, and
Pharmacology, Creighton University Health Sciences Center,
Omaha, NE 68178, USA
2University of Nebraska Medical Center, Omaha, NE 68198, USA
We have previously compared selected antioxidants including
vitamins C and E, -carotene and a novel IH636 grape seed
proanthocyanidin extract (GSPE) with respect to their scavenging
abilities against biochemically generated free radicals in both
in vitro and in vivo models. The results demonstrated that GSPE
is a significantly more potent oxygen free radical scavenger
compared with vitamins C and E and -carotene. GSPE has been
reported to exhibit a wide range of biological and
pharmacological activities including free radical scavenging,
antibacterial, antiviral, antiinflammatory, antiallergic and
vasodilator actions. In this study hydrogen peroxide-induced
oxidative damage was assessed in macrophage J774A.1 and
neuroactive adrenal pheochromocytoma PC-12 cells, and the
concentration-dependent ability of GSPE to protect these cells.
Laser scanning confocal microscopy was used to determine
intracellular oxidized states. Approximately 5.8- and 4.5-fold
increases in fluorescence intensity were observed following
incubation of macrophage J774A.1 and PC-12 cells with 0.50 mM
H2O2 for 24 h, respectively. Pretreatment of the J774A.1
cells with 50 mg/L and 100 mg/L GSPE decreased
H2O2-induced fluorescence intensity by 36% and 70%,
respectively, while under these same conditions approximately
50% and 70% decreases in fluorescence intensities were observed
in PC-12 cells. The results indicate that hydrogen peroxide
significantly increases oxidative stress in these cells as
demonstrated by the increase in intracellular oxidized states.
Furthermore, GSPE can significantly protect against hydrogen
peroxide-induced oxidative stress in cultured J774A.1 macrophage
and neuronal PC-12 cells. Copyright © 1998 John Wiley &
Sons, Ltd.
ar61
Environmental and Molecular Mutagenesis
Volume 35, Issue 2, 2000. Pages:
86-98
Differential modulation of the genotoxicity of food
carcinogens by naturally occurring monomeric and dimeric
polyphenolics
Fenton Catterall 1, Jean-Marc Souquet 2, Veronique Cheynier 2,
Sonia de Pascual-Teresa 3, Celestino Santos-Buelga 3, Michael N.
Clifford 1, Costas Ioannides 1 *
1School of Biological Sciences, University of Surrey, Guilford,
Surrey, United Kingdom
2Unité de Recherche Biopolymères et Arômes, INRA, Montpellier
Cedex, France
3Nutricion y Bromatologia, Facultad de Farmacia, Campus Miguel
de Unamuno, Salamanca, Spain
Naturally occurring dimeric polyphenolics and their gallate
esters were isolated from grape seeds, almond fruits, and apple
skin, and their ability to modulate the mutagenicity of food
carcinogens was studied in the Ames test, and compared to that
of the monomeric green tea flavonols, (+)-catechin and
(-)-epicatechin. Neither the monomeric nor the dimeric
polyphenols and their galloylated derivatives influenced the
mutagenic activity elicited by the indirectly acting food
carcinogens benzo[a]pyrene and
2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), in the presence
of a hepatic activation system derived from Aroclor 1254-treated
rats; the only exception was the B7 dimer, which, at
concentrations above 1 M, suppressed the mutagenicity of IQ.
None of the polyphenolics modulated the mutagenic activity
elicited by the directly acting carcinogen
N-methyl-N-nitro-nitrosoguanidine (MNNG). In contrast, all the
dimeric polyphenols and the galloylated metabolites, at
concentrations over 1 M, potentiated the mutagenic activity
induced by the indirectly acting carcinogen
N-nitrosopyrrolidine, in the presence of an activation system
derived from isoniazid-treated rats. In conclusion, dimeric
polyphenols and galloylated derivatives of plant origin are
unlikely to influence the initiation stage of the
carcinogenicity of chemicals through mechanisms that involve
inhibition of their cytochrome P450-mediated bioactivation or
scavenging of the reactive, genotoxic intermediates. Environ.
Mol. Mutagen. 35:86-98, 2000 © 2000 Wiley-Liss, Inc.
ar62
Journal of the Science of Food and
Agriculture
Volume 80, Issue 1, 2000. Pages: 91-101
Modulation of the mutagenicity of food carcinogens by
oligomeric and polymeric procyanidins isolated from grape
seeds: synergistic genotoxicity with N-nitrosopyrrolidine
Fenton Catterall 1, Jean-Marc Souquet 2, Veronique Cheynier 2,
Michael N Clifford 1, Costas Ioannides 1 *
1School of Biological Sciences, University of Surrey, Guildford,
Surrey GU2 5XH, UK
2Unité de Recherche Biopolymères et Arômes, INRA, Place Viala,
F-34060 Montpellier Cedex, France
Oligomeric and polymeric procyanidins were isolated from grape
seeds, and their antimutagenic potential against food
carcinogens was evaluated in the Ames test. Both procyanidins
suppressed the mutagenicity of IQ and benzo[a]pyrene but did not
modulate the mutagenic activity of MNNG. At the concentrations
where antimutagenic activity was expressed, the oligomeric and
polymeric procyanidins inhibited the hepatic O-dealkylation of
methoxy- and ethoxyresorufin. It is concluded that the
antimutagenic activity exhibited by oligomeric and polymeric
procyanidins is the consequence of inhibition of CYP1A-mediated
bioactivation. In contrast with these findings, oligomeric and
polymeric procyanidins potentiated the mutagenicity of
N-nitrosopyrrolidine; the monomeric tea flavanols (+)-catechin
and (-)-epicatechin also elicited the same effect. Both the
flavanols and procyanidins, at the concentrations studied,
failed
to
elicit a mutagenic response in the Ames test, either in the
presence or absence of an activation system. Incorporation of
catalase and superoxide dismutase to the activation system
failed to prevent the synergistic effect between (+)-catechin
and the nitrosamine. The mutagenic activity of
N-nitrosopyrrolidine was much higher when the bacteria were
grown in nutrient broth supplemented with (+)-catechin compared
with bacteria grown in nutrient broth alone. It may be
cautiously inferred that the synergistic genotoxicity between
polyphenolics and N-nitrosopyrrolidine involves interaction of
(+)-catechin with bacterial DNA, facilitating the covalent
binding of the ultimate carcinogens of the nitrosamine to the
DNA.
©
2000 Society of Chemical Industry
ar64
J Invest Dermatol 1999
Mar;112(3):310-6
Procyanidin oligomers selectively and intensively promote
proliferation of mouse hair epithelial cells in vitro and
activate hair follicle growth in vivo.
Takahashi T, Kamiya T, Hasegawa A, Yokoo Y
Tsukuba Research Laboratories, Kyowa Hakko Kogyo, Ibaraki,
Japan.
We have previously reported that proanthocyanidins extracted
from grape seeds possess growth-promoting activity toward murine
hair epithelial cells in vitro and stimulate anagen induction in
hair cycle progression in vivo. This report constitutes a
comparison of the growth-promoting activity of procyanidin
oligomers and the target cells of procyanidins in the skin.
Results show that procyanidin dimer and trimer exhibit higher
growth-promoting activity than the monomer. The maximum
growth-promoting activity for hair epithelial cells with
procyanidin B-2, an epicatechin dimer, reached about 300% (30
microM) relative to controls (= 100%) in a 5 d culture. Optimum
concentration of procyanidin C-1, an epicatechin trimer, was
lower than that of procyanidin B-2; the maximum growth-promoting
activity of procyanidin C-1 was about 220% (3 microM). No other
flavonoid compounds examined exhibit higher proliferative
activities than the procyanidins. In skin constituent cells,
only epithelial cells such as hair keratinocytes or epidermal
keratinocytes respond to procyanidin oligomers. Topical
application of 1% procyanidin oligomers on shaven C3H mice in
the telogen phase led to significant hair regeneration
[procyanidin B-2, 69.6% +/- 21.8% (mean +/- SD); procyanidin
B-3, 80.9% +/- 13.0%; procyanidin C-1, 78.3% +/- 7.6%] on the
basis of the shaven area; application of vehicle only led to
regeneration of 41.7% (SD = 16.3%). In this paper, we
demonstrate the hair-growing activity of procyanidin oligomers
both in vitro and in vivo, and their potential for use as agents
to induce hair growth.
PMID:
10084307, UI: 99181798
ar65
Acta Derm Venereol 1998
Nov;78(6):428-32
Proanthocyanidins from grape seeds promote proliferation of
mouse hair follicle cells in vitro and convert hair cycle in
vivo.
Takahashi T, Kamiya T, Yokoo Y
Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Ibaraki,
Japan.
For the purpose of discovering natural products which possess
hair growing activity, we examined about 1000 kinds of plant
extracts concerning growth-promoting activity with respect to
hair follicle cells. After an extensive search, we discovered
that proanthocyanidins extracted from grape seeds promote
proliferation of hair follicle cells isolated from mice by about
230% relative to controls (100%); and that proanthocyanidins
possess remarkable hair-cycle-converting activity from the
telogen phase to the anagen phase in C3H mice in vivo test
systems. The profile of the active fraction of the
proanthocyanidins was elucidated by thiolytic degradation and
tannase hydrolysis. We found that the constitutive monomers were
epicatechin and catechin; and that the degree of polymerization
was 3.5. We demonstrated the possibility of using the
proanthocyanidins extracted from grape seeds as agents inducing
hair growth.
PMID:
9833041, UI: 99050235
ar66
J Invest Dermatol 1997
Apr;108(4):495-500
Hair cycle stage of the mouse vibrissa follicle determines
subsequent fiber growth and follicle behavior in vitro.
Robinson M, Reynolds AJ, Jahoda CA
Department of Biological Sciences, University of Durham, United
Kingdom.
The establishment of culture models representative of all
aspects of in vivo hair follicle behavior is an important goal
for theoretic and analytic studies. Rodent vibrissa follicles
have regular, predictable, and relatively short growth cycles.
In this investigation, we took advantage of these properties; we
classified mouse vibrissa follicles according to different
phases in the hair cycle and then compared fiber growth and
morphologic changes in culture. Follicles isolated in the early
phase of the growth cycle produced fine growing fibers with an
average growth that exceeded 3 mm over 15 d. Even when hair
growth had slowed or halted subsequently, histology showed that
these follicles retained an anagen-like morphology. By contrast,
follicles isolated toward the end of the growing cycle produced
thicker fibers for much shorter periods, after which growth
ceased and the fibers lifted up from the base of the follicle.
Internally, these specimens resembled their telogen counterparts
in situ. Follicles isolated in mid-growth demonstrated
intermediate fiber growth characteristics. In organ culture,
mouse vibrissa follicles therefore closely reflect their in vivo
origin in growth characteristics and cycle timing. These data
provide new opportunities for studying hair growth cycle
mechanisms in vitro, but present a caveat for quantitative
studies because there may be a greater growth cycle-related
variation than has previously been assumed.
PMID:
9077480, UI: 97232205
ar67
Exp Dermatol 1999
Aug;8(4):317-9
In vitro maintenance of isolated hair follicles: current
status and future development.
Philpott M
Department of Anatomy, St Bartholomew's and the Royal London
School of Medicine and Dentistry.
ar68
Planta Med 1980;Suppl:84-90
Bioassay of crude drugs for hair growth promoting activity in
mice by a new simple method.
Tanaka S, Saito M, Tabata M
PMID: 7454882, UI: 81101527
ar69
Rev Med Liege 1997
Oct;52(10):671-4
Hair follicles and hair growth cycles: recent considerations
Pierard-Franchimont C, Pierard GE
Service de Dermatopathologie, Universite de Liege.
ar70
Arch Klin Exp Dermatol 1966;227(1):390-409
Histology and anatomy of the hair follicle in the course of
the hair cycle
Bandmann
HJ, Bosse K
ar71
Pharmacol Appl Skin Physiol 2000
May-Aug;13(3-4):133-42
Several selective protein kinase C inhibitors including
procyanidins promote hair growth.
Takahashi T, Kamimura A, Shirai A, Yokoo Y
Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Tsukuba,
Ibaraki, Japan. tomoya.takahashi@kyowa.co.jp
We have previously reported that procyanidin oligomers
selectively promote growth of murine hair epithelial cells in
vitro and stimulate anagen induction in vivo. We report here the
possible relationship between the protein kinase C-inhibiting
activity of procyanidins and their hair-growing activity. Of the
procyanidins, procyanidin B-2 and procyanidin C-1, which
selectively inhibit protein kinase C, intensively promote hair
epithelial cell proliferation in vitro and stimulate anagen
induction in vivo. On the other hand, procyanidins, which
inhibit
both
protein kinase C and A, showed relatively low activity in in
vitro and in vivo evaluations. We also found that calphostin C,
which is a selective inhibitor of protein kinase C, possesses
hair epithelial cell growth-promoting activity in vitro and
anagen phase-inducing hair-growing activity in vivo. Other
selective protein kinase C inhibitors, such as
hexadecylphosphocholine, palmitoyl-DL-carnitine chloride, and
polymyxin B sulfate, also show marked anagen phase-inducing
hair-growing activity in vivo. Nonselective protein kinase
inhibitors, such as staurosporine and K252a, inhibit the growth
of hair epithelial cells. 1,2-Dioctanoyl-sn-glycerol, a protein
kinase C activator, dose-dependently decreases the growth of
hair epithelial cells. Forskolin, an adenylate cyclase
activator, promotes hair epithelial cell growth and boosts the
growth-promoting effect of procyanidin B-2. It is speculated
that the hair-growing activity of procyanidins is related to
their protein kinase C-inhibiting activity. Copyright 2000 S.
Karger AG, Basel
PMID:
10859531, UI: 20319197
ar72
Hepatogastroenterology 1994
Aug;41(4):343-8
Role of free radicals in liver diseases and hepatic fibrosis.
Britton RS, Bacon BR
Department of Internal Medicine, St. Louis University Health
Sciences Center, Missouri.
An increased production of free radicals in the liver has been
implicated in a variety of liver diseases. Free radicals can
damage cellular macromolecules and, therefore, may participate
in hepatocellular injury when produced in excess. Strong
evidence exists for hepatic free radical production in animal
models of iron and copper overload, ethanol consumption, and
ischemia-reperfusion. Although less is known about the situation
in humans with liver diseases, the available evidence is
consistent with the findings in animal experiments. Treatments
that reduce free radical production and/or levels have
protective effects in hepatic ischemia-reperfusion. Free
radical-initiated lipid peroxidation may play a role in hepatic
fibrogenesis, perhaps through an effect of aldehydic
peroxidation products on Kupffer cells and lipocytes. This
hypothesis is supported by the observation that dietary
supplementation with vitamin E has a protective effect on carbon
tetrachloride-induced hepatic fibrosis. While cellular damage in
human liver diseases is probably multifactorial, free radicals
may play important roles in initiating and/or perpetuating this
damage.
ar73
Arch Biochem Biophys 1999
Sep 1;369(1):42-58
A novel proanthocyanidin IH636 grape seed extract increases in
vivo Bcl-XL expression and prevents acetaminophen-induced
programmed and unprogrammed cell death in mouse liver.
Ray SD, Kumar MA, Bagchi D
Department of Pharmacology, Toxicology & Medicinal
Chemistry, Arnold & Marie Schwartz College of Pharmacy and
Health Sciences, Brooklyn, New York, 11201, USA.
Several molecular events in the apoptotic or necrotic death of
hepatocytes induced by acetaminophen (AAP) now appear to be well
defined. Recent studies also indicate that select expression of
bcl-Xl is possibly modified during AAP-induced liver injury. The
purpose of this study was several-fold: (i) to examine the
hepatoprotective ability of short-term (3-day) and long-term
(7-day) exposures of a grape seed proanthocyanidin extract
(GSPE) on AAP-induced liver injury and animal lethality; (ii) to
monitor effects of GSPE on one of the prime targets of AAP,
i.e., hepatocellular genomic DNA and associated apoptotic and
necrotic death; and (iii) to unravel changes in the pattern of
expression of an antiapoptotic gene, bcl-Xl in the liver. In
order to investigate these events, male ICR mice (30-40 g) were
administered nontoxic doses of GSPE (3 or 7 days, 100 mg/kg,
po), followed by hepatotoxic doses of AAP (400 and 500 mg/kg,
ip), and sacrificed 24 h later. Serum was analyzed for alanine
aminotransferase activity (ALT) and the liver for
histopathological diagnosis of apoptosis/necrosis. The ability
of AAP to promote apoptotic DNA fragmentation and its
counteraction by GSPE in the liver was also evaluated
quantitatively (by a sedimentation assay) and qualitatively (by
agarose gel electrophoresis). Portions of livers were also
subjected to Western blot analysis (27,000g fraction of liver
homogenates) to examine the pattern of expression of cell death
inhibitory gene bcl-Xl. Results indicate that 7-day GSPE
preexposure induced dramatic protection and markedly decreased
liver injury and animal lethality culminated by AAP, when
compared to a short-term 3-day exposure. Abrogation of toxicity
was also mirrored in DNA fragmentation. Histopathological
evaluation of liver sections showed remarkable counteraction of
AAP-toxicity by this novel GSPE and substantial inhibition of
both apoptotic and necrotic liver cell death. Agarose gel
electrophoresis revealed that 7-day GSPE preexposure prior to
AAP administration completely blocked
Ca(2+)/Mg(2+)-Ca(2+)/Mg(2+)-dependent-endonuclease-mediated
ladder-like fragmentation of genomic DNA and significantly
altered the bcl-Xl expression. The most dramatic changes
observed in this study were: (i) substantial increase in the
expression of bcl-Xl in the liver by 7-day GSPE exposure alone;
(ii) significant modification bcl-Xl expression by AAP alone;
and (iii) dramatic inhibition of AAP-induced modification of
bcl-Xl (phosphorylation?) expression by GSPE. In summary, these
observations demonstrate that GSPE preexposure may significantly
attenuate AAP-induced hepatic DNA damage, apoptotic and necrotic
cell death of liver cells, and, most remarkably, antagonize the
influence of AAP-induced changes in bcl-Xl expression in vivo.
Copyright 1999 Academic Press.
ar74
Vopr Med Khim 1995 Mar-Apr;41(2):20-3
"Effect of natural complexes of biologically active substances
on liver regeneration in alcohol poisoning."
Kushnerova NF, Fomenko SE, Polozhentseva MI, Bulanov AE,.
Hepatoprotective effect of natural substances obtained from
extracts of grape combs, leaves of green and black tea were
studied in liver tissue of ethanol-consuming rats by means of
evaluation of the neutral lipid fractions and phospholipids as
well as by measurement of glucose and nicotinamide coenzymes
NAD+ and NADP in blood. In all the animal groups treated with
these vegetable extracts content of total phospholipids,
decreased after the ethanol treatment, was increased, while
fraction composition of phospholipids and of neutral lipids was
normalized; in blood content of glucose, NAD+ and NADP
approached to control values. These results suggest that the
vegetable extracts studied exhibited the hepatoprotective
effect in alcohol intoxication.
ar77
Biol Pharm Bull 1995 Oct;18(10):1347-51
"Grape extract inhibits lipid peroxidation of human low
density lipoprotein."
Lanningham-Foster L, Chen C, Chance DS, Loo G
Some epidemiological data have linked dietary polyphenols with
lower risk of coronary heart disease. Polyphenols might impair
lipoprotein oxidation which is believed to be an important step
in initiating atherogenesis. The purpose of this study was to
determine if grape extract known to contain polyphenolic
substances can block copper-induced oxidative modification of
human low density lipoprotein (LDL).LDL oxidation was monitored
spectrophotometrically by measurement of change in absorbance at
234 nm. Incubation of LDL (0.05 mg protein/ml) with 1.66 microM
cupric chloride produced a lag phase of 130 min before onset of
the propagation phase where polyunsaturated fatty acids undergo
conversion to conjugated lipid hydroperoxides. However, in the
presence of grape extract at a final concentration equal to an
8000-fold dilution, the lag phase was extended to 185 min. A
4000-fold and 2000-fold dilution of grape extract produced lag
phases of 250 and 465 min, respectively. LDL oxidation was
essentially blocked for at least 10 h with a 1000-fold dilution
of grape extract. In other experiments, incubation of LDL (0.2
mg protein/ml) with 5 microM cupric chloride for 1-4 h increased
both thiobarbituric acid-reactive substances and electrophoretic
mobility of LDL on agarose gel. In addition, there was loss of
immunoreactivity of LDL with a murine monoclonal antibody
against human apolipoprotein B-100. However, these oxidative
changes to LDL by copper were prevented when diluted grape
extract was present during incubation. It is concluded that
grape extract contains antioxidants in the form of polyphenols
with the capacity to inhibit oxidative modification of LDL.
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