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Life Extension Magazine

LE Magazine May 2002

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Studies from throughout the world that can help you live longer

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May 2002 Table of Contents

  1. Antioxidant supplementation reverses age-related neuronal changes
  2. Safflower oil vs. perilla oil on lipid metabolism
  3. Chronic pancreatitis and antioxidant therapy
  4. Curcumin and cell membrane dynamics
  5. Effects of antioxidants on metabolism of the eye and brain
  6. DHEAS decreases overactivity of immune system
  7. Grape seed extract weakens development of atherosclerosis
  8. Tamoxifen-DNA adducts detected in the endometrium of women
  9. Treatment of parasites with Amphotericin B

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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