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LE Magazine May 2002
Studies
from throughout the world that can help you live
longer
May 2002 Table of
Contents
1. Antioxidant supplementation reverses
age-related neuronal changes
Evidence suggests that free radicals in the brain may play a
role in the development of age-related neuronal impairments.
The increase in the concentration of the proinflammatory
cytokine (cells which regulate immune responses),
interleukin-1 beta (can cause fever, induce synthesis of acute
phase proteins, and initiate metabolic wasting), in aged brain
tissue, may also be a contributory factor. This study analyzed
changes in enzymatic and nonenzymatic antioxidant levels, in
parallel with interleukin-1 beta concentration, in cortical
brain tissue prepared from young and aged rats. Results showed
an age-related increase in the activity of superoxide
dismutase and an age-related decrease in the concentrations of
vitamin E and C. These observations, coupled with age-related
increases in lipid peroxidation and interleukin-1 beta
concentration, show a compromised antioxidant defense in the
cortex of aged rats. These negative changes were not observed
in cortical tissue prepared from rats fed on a diet
supplemented with vitamin E and C for 12 weeks.
NEUROBIOLOGY OF AGING, 1998, Vol 19,
Iss 5, pp 461-467
2. Safflower
oil vs. perilla oil on lipid metabolism
Diets high in linoleic acid (20% safflower oil contained
77.3% linoleic acid, SO-diet) and a-linolenic acid (20%
perilla oil contained 58.4% alpha-linolenic acid, PO-diet)
were fed to rats for 3, 7, 20, and 50 days, and effects of the
diets on lipid metabolism were compared. Levels of serum total
cholesterol and phospholipids in the rats fed the PO-diet were
markedly lower than those fed the SO-diet after the seventh
day. In blood and liver phosphatidylcholine, the proportion of
n-3 fatty acids showed a greater increase in the PO group than
in the SO group. The results indicate that alpha-linolenic
acid (perilla oil) has more potent serum cholesterol-lowering
ability than linoleic acid (safflower oil) both in short and
long feeding terms.
COMPARATIVE BIOCHEMISTRY AND
PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 1998, Vol
121, Iss 2, pp 223-231
3. Chronic
pancreatitis and antioxidant therapy
According to The Manchester 'oxidant stress' hypothesis for
the development of pancreatitis, oxidant stress, mainly from
reactive foreign substances, are perceived as the key cause of
disease in chronic pancreatitis, and by depleting glutathione,
targets the exocytosis mechanism (process whereby cell
membrane ruptures) of the pancreatic acinar cell. Inhalation
exposure to petrochemical products is identified as an
independent risk factor in patients at Manchester Royal
Infirmary, where some 50% of patients referred have
non-alcoholic disease. This paper describes the development of
antioxidant therapy, using supplements of methionine, vitamin
C and selenium, and its validation in a placebo-controlled
trial, followed by a retrospective cross-sectional study in 94
consecutive patients for an average of 30 months. Antioxidant
therapy emerges as a safe and effective medical alternative to
surgery for painful chronic pancreatitis.
DIGESTION, 1998, Vol 59, Suppl. 4, pp
36-48
4. Curcumin
and cell membrane dynamics
Curcumin is a well-known natural compound with
anti-inflammatory properties. Its antiproliferative effect and
ability to modulate apoptosis (programmed cell death) are
considered essential in cancer therapy. Due to the properties
of curcumin, it targets local membranes. This prompted an
investigation of the mechanisms of membrane changes evoked by
curcumin. Curcumin was found to expand the cell membrane,
inducing echinocytosis (overabundance of prickly cells).
Changes in cell shape were accompanied by transient exposure
of phosphatidylserine. Membrane disproportion was recovered by
the action of an enzyme, which remained active in the presence
of curcumin. Lipids rearrangements and drug partitioning
caused changes of lipid fluidity. Based on these results,
curcumin would produce various incidents of beneficial
apoptosis.
EXPERIMENTAL CELL RESEARCH, 1998, Vol
245, Iss 2, pp 303-312
5. Effects of
antioxidants on metabolism of the eye and brain
Metabolic abnormalities observed in the retina of the eye and
in the cerebral cortex of the brain were compared in diabetic
rats. Diabetes of 2 months duration significantly increased
oxidative stress in the retina, as shown by elevation of
retinal thiobarbituric acid reactive substances (TEARS) and
lower than normal activities of antioxidant defense enzymes,
but had no such effect in the cerebral cortex. Other enzyme
activities were below normal in the retina and cerebral
cortex. In contrast, protein kinase C (PKC) activity was
elevated in the retina but not in the cerebral cortex in the
same hyperglycemic rats. Supplementation with an antioxidant
mixture (containing vitamin C, Trolox, vitamin E acetate,
N-acetyl cysteine, beta-carotene, and selenium) prevented the
diabetes-induced elevation of free radical stress to the
retina. In the cerebral cortex, administration of the
antioxidant diet also prevented the diabetes-induced decreases
in various enzymes, but had no effect on TEARS and activities
of antioxidant-defense enzymes. The results indicate that the
cerebral cortex is more resistant than the retina to
diabetes-induced oxidative stress and that supplementation
with these antioxidants offers a means to inhibit multiple
hyperglycemia-induced retinal metabolic abnormalities.
FREE RADICAL BIOLOGY AND MEDICINE,
1999, Vol 26, Iss 3-4, pp 371-378
6. DHEAS
decreases overactivity of immune system
Dehydroepiandrosterone sulfate (DHEAS) has been involved in
the regulation of cellular immunity. The aim of this study was
to evaluate whether the age-dependent reduction of DHEAS was
associated with changes of natural killer (NK) immune function
in healthy elderly subjects and in patients with senile
dementia (SD) of the Alzheimer type (SDAT). DHEAS was
significantly reduced in healthy elderly subjects SD = 2.3 mu
mol/l) and SDAT (1.6 mu mol/l) patients compared to healthy
young subjects (6.7 mu mol/l); significant differences were
also found when healthy elderly subjects and SDAT patients
were compared. A significant opposite association between age
and DHEAS levels was demonstrated in SDAT and healthy elderly
subjects. The decrease in 24-hour DHEAS secretion was
associated with a higher NK cytotoxic response to DHEAS in the
healthy elderly subject group than in healthy subjects of
young age. Increased NK cell activity was found in patients
with SDAT in comparison with the healthy elderly subject. On
the contrary, NK cell cytotoxic response of SDAT patients was
less pronounced during DHEAS exposure and when DHEAS was
coincubated with IL-2. These data suggest a role of DHEAS in
the immune system on NK functional activity in physiological
aging and SDAT. Thus, DHEAS has a reducing effect on the
overactivity of Natural Killer immune cells during exposure
with cytokines. This effect of DHEAS might work stop the
pathogenesis and progression of disease by counteracting
related neuroimmune components.
DEMENTIA AND GERIATRIC COGNITIVE
DISORDERS, 1999, Vol 10, Iss 1, pp 21-27
7. Grape seed
extract weakens development of atherosclerosis
The aim of this study was to evaluate the antiatherosclerotic
effect of proanthocyanidin-rich extracts from grape seeds in
cholesterol-fed rabbits. 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. In an in vitro experiment using human
blood, proanthocyanidin-rich extract, which was added to the
blood, inhibited the oxidation of LDL. These results suggested
that proanthocyanidins, the major polyphenols in red wine,
might trap free radicals in blood and interstitial fluid of
the arterial wall, thereby inhibiting oxidation of LDL and
showing an antiatherosclerotic activity.
ATHEROSCLEROSIS, 1999, Vol 142, Iss
1, pp 139-149
8. Tamoxifen-DNA adducts detected in the
endometrium of women
According to this study, women treated for breast cancer with
tamoxifen are at increased risk of developing endometrial
cancer. This carcinogenic effect has been attributed to
estrogenic stimulation and/or to a genotoxic effect of this
drug. (Genotoxic denotes a substance that is damaging to DNA,
thus capable of causing mutation or cancer). To examine
genotoxicity, this study developed a procedure for analyzing
tamoxifen-DNA adducts (an adduct is a complex that forms when
a chemical binds to a biological molecule, such as DNA or a
protein) in endometrial tissue. This test is several orders of
magnitude more sensitive than those previously used for
detecting tamoxifen-DNA adducts. Endometrial tissue was
obtained from women undergoing tamoxifen therapy and from
untreated control subjects. DNA adducts of alpha-
(N-2-deoxyguanosinyl) tamoxifen, were detected in six of 13
patients in the tamoxifen-treated group. Levels of adducts
ranged from 0.5 to 8.3 and from 0.4 to 4.8 adducts/10(8)
nucleotides, respectively. Tamoxifen-DNA adducts were not
detected in endometrial tissue obtained from the control
subject. This study concluded that one or more tamoxifen
metabolites react with endometrial DNA to form covalent
adducts, establishing the potential genotoxicity of this drug
for women and it suggests the use of tamoxifen-DNA adducts as
biomarkers for investigations of tamoxifen-induced endometrial
cancer.
CHEMICAL RESEARCH IN TOXICOLOGY,
1999, Vol 12, Iss 7, pp 646-653
9. Treatment
of parasites with Amphotericin B
Amphotericin B is an effective agent against the parasitic
protozoa Leishmania that causes leishmaniasis (an infection
transmitted by sand flies). However, its use is limited by
drug toxicity. The development of less toxic,
lipid-encapsulated formulations of amphotericin B has made
these formulations available for testing against visceral
leishmaniasis. This study used Amphotericin B Colloidal
Dispersion (ABCD) to treat Brazilian kala-azar. (Kala-azar is
a fatal infectious disease endemic in the tropics and
subtropics, caused by Leishmania and marked by fever, anemia,
wasting, splenomegaly and hepatomegaly). Miraculously, 10 of
10 patients were cured with 2 mg/kg/day for 10 days; nine of
nine patients were cured with 2 mg/kg/day for seven days; nine
of 10 patients were cured with 2 mg/ kg/day for five days. The
ability to cure 90% of kala-azar patients with a regimen of
merely five days is remarkable, considering that 20 to 40 days
of treatment with toxic radicals and a 28 to 40 day course
(every-other-day) of amphotericin B deoxycholate therapy
(detergent to make membrane proteins water soluble) are
otherwise needed. Although ABCD did frequently cause a
syndrome of fever and respiratory distress during infusion for
children less than six years of age, the virtual absence of
kidney toxicity was striking.
CHEMOTHERAPY, 1999, Vol 45, Suppl. 1,
pp 54-66
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