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PubMed1986

Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms.

Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. We examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems and peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 microM Na2SeO3 (selenium) or with 7 microM alpha-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. Cells pretreated with vitamin E did not show these biochemical effects, and the combined pretreatment with vitamin E and selenium did not augment the effect of selenium on these parameters. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by an alternate complementary mechanism.

Animals↗
PubMed2001

Selenium metabolism in Drosophila: selenoproteins, selenoprotein mRNA expression, fertility, and mortality.

Selenocysteine is a rare amino acid in protein that is encoded by UGA with the requirement of a downstream mRNA stem-loop structure, the selenocysteine insertion sequence element. To detect selenoproteins in Drosophila, the entire genome was analyzed with a novel program that searches for selenocysteine insertion sequence elements, followed by selenoprotein gene signature analyses. This computational screen and subsequent metabolic labeling with (75)Se and characterization of selenoprotein mRNA expression resulted in identification of three selenoproteins: selenophosphate synthetase 2 and novel G-rich and BthD selenoproteins that had no homology to known proteins. To assess a biological role for these proteins, a simple chemically defined medium that supports growth of adult Drosophila and requires selenium supplementation for optimal survival was devised. Flies survived on this medium supplemented with 10(-8) to 10(-6) m selenium or on the commonly used yeast-based complete medium at about twice the rate as those on a medium without selenium or with >10(-6) m selenium. This effect correlated with changes in selenoprotein mRNA expression. The number of eggs laid by Drosophila was reduced approximately in half in the chemically defined medium compared with the same medium supplemented with selenium. The data provide evidence that dietary selenium deficiency shortens, while supplementation of the diet with selenium normalizes the Drosophila life span by a process that may involve the newly identified selenoproteins.

Algorithms↗
PubMed2001

Selenium, selenoproteins and human health: a review.

Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.

Glutathione Peroxidase↗
PubMed1982

Influence of diet on the effects of selenium in the genesis of mammary tumors.

Two experiments were conducted to study the interaction of various diets with selenium in the genesis of mammary tumors. In the first experiment, virgin C3H mice were fed either an Oregon State University (O.S.U.) chow or this chow plus 0.5 or 2.0 ppm selenium in the drinking water, or Wayne Lab-Blox Chow with or without 2.0 ppm selenium in the water. Selenium significantly reduced the tumor incidence in mice fed the O.S.U. chow, but not in those fed the Wayne chow. In the second experiment, virgin female C3H mice were fed a purified casein-based diet with either lard, butter, corn oil, or rapeseed oil at a 10% level without or with selenium (2 ppm) in the drinking water. Selenium had no significant effect upon tumor incidence in this experiment. Thus, these results indicate that the type of diet has a marked influence on the beneficial effects of selenium in reducing mammary tumors in C3H mice.

Animals↗
PubMed1992

Mammary cancer prevention by regular garlic and selenium-enriched garlic.

The anticarcinogenic activities of regular (soil-grown) garlic and selenium-enriched garlic (cultivated in the greenhouse) were evaluated using the 7,12-dimethylbenz[a]anthracene-(DMBA) induced mammary tumor model in rats. In Experiment 1, milled regular garlic powder was added to the basal AIN-76A diet at 20 g/kg. The results from different schedules of supplementation suggested that a continuous treatment, which started before DMBA and persisted for the entire duration of the study, was most effective in tumor suppression. In Experiment 2, selected allyl group-containing sulfides that are normal constituents of garlic extract were given by gavage in three single doses immediately before DMBA. Several structurally related compounds were found to be protective during the initiation phase in the mammary cancer model. Although the present study was not designed specifically to elucidate the structure-activity relationship with respect to sulfur chain length or alkyl versus alkenyl substitution, our data showed that diallyl disulfide was more active than diallyl sulfide or allyl methyl sulfide. In Experiment 3, the anticarcinogenic activity of selenium-enriched garlic (containing 150 ppm Se dry weight from growth in a selenium-fertilized medium) was compared with that of regular garlic as well as selenite. Animals given the selenium-enriched garlic (final concentration 3 ppm Se in the diet) developed the fewest mammary tumors. Tissue selenium levels, however, were lower in these animals than in those fed the same amount of selenium from selenite. Our study demonstrated the feasibility of achieving cancer prevention with the use of a selenium-rich food system.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial.

INTRODUCTION: Selenium is an essential trace element with antioxidant properties. Trials with selenium have been conducted in rheumatoid arthritis (RA) to correct impaired selenium status and increase defences against deleterious oxidant species. AIM OF THE STUDY: To investigate in a double blind multi-centric placebo-controlled study the effects of selenium supplementation in RA. METHODS: Fifty five patients with moderate RA received during 90 days either capsules containing selenium-enriched yeast (200 microg/d) or a placebo. RESULTS: The visual analog scale, the Ritchie index, the number of swollen and painful joints, and morning stiffness significantly decreased with time in both groups (p<0.001), but no difference between groups could be identified. When examining the quality of life a significant (p<0.01) improvement in arm movements and health feeling was evidenced in selenium-treated patients. CONCLUSION: Selenium treatment did not show clinical benefit on RA. Interestingly, the improval in both groups demonstrated a placebo effect of the intervention trial.

Adolescent↗
PubMed2005

Low contribution of rice and vegetables to the daily intake of selenium in Japan.

The growing interest in the prevention role of selenium in certain degenerative diseases such as cancer and cardiovascular disease has fostered research on natural sources of selenium. In this research, total selenium concentrations in over 120 items of selected Japanese foods were determined. The selenium concentration was measured fluorometrically by measurement of the fluorescence of piazselenol resulting from the reaction of selenite with 2, 3-diaminonaphtalene. The selenium level in rice, which is the staple food consumed in Japan, is lower than the other countries. But the mean levels of selenium in meat and fish products are among the highest values reported in other countries. Although the numbers of samples of selected foods analyzed are small, the results describe the picture of the selenium level of Japanese foods.

Food Analysis↗
PubMed2006

Neural network-based analysis of thiol proteomics data in identifying potential selenium targets.

Generation of a monomethylated selenium metabolite is critical for the anticancer activity of selenium. Because of its strong nucleophilicity, the metabolite can react directly with protein thiols to cause redox modification. Here, we report a neural network-based analysis to identify potential selenium targets. A reactive thiol specific reagent, BIAM, was used to monitor thiol proteome changes on 2D gel. We constructed a dynamic model and evaluated the relative importance of proteins mediating the cellular responses to selenium. Information from this study will provide new clues to unravel mechanisms of anticancer action of selenium. High impact selenium targets could also serve as biomarkers to gauge the efficacy of selenium chemoprevention.

Antineoplastic Agents↗
PubMedDate not supplied

Acute and subchronic toxicity studies on Sel-Plex, a standardized, registered high-selenium yeast.

Selenium has been recognized as an essential nutrient for human health; however, its bioavailability is primarily dependent upon the type of selenium, elemental versus organic. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast (Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). The present studies were conducted to investigate potential oral toxicity of a unique selenized yeast preparation (Sel-Plex) when administered to (1) adult female CHS Swiss mice ICo:OFI (IOPS Caw); (2) adult female CHS Sprague-Dawley rats; and (3) adult male and female Sprague-Dawley CD rats. For the 28- and 90-day toxicity studies, (1) adult male and female Sprague-Dawley CRL:CD(R)(SD) IGS BR strain rats and (2) adult male and female 6- to 7-month-old Beagle dogs were used. The LD50 for mice was >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg) and for rats, was greater than >or=2000 mg Sel-Plex/kg (>or=4.06 mg Se/kg). In the two 28-day studies, for rats, the no observed adverse effects level (NOAEL) was 50 mg Sel-Plex/kg/day (0.1 mg Se/kg/day), and for the dogs, the NOAEL was 22.5 mg Sel-Plex/kg/day (0.045 mg Se/kg/day). For the two 90-day studies, for rats the NOAEL for Sel-Plex was 114 mg/kg/day (0.23 mg Se/kg/day), and for dogs, the NOAEL was 30 mg Sel-Plex/kg/day (0.06 mg Se/kg/day): the latter being the NOAEL in the most sensitive species.

Animals↗
PubMedDate not supplied

Effect of selenium on distribution, demethylation, and excretion of methylmercury by the guinea pig.

The influence of selenium on methylmercury excretion, organ and subcellular distribution, and demethylation was studied in the guinea pig at different times following a single equimolar dose (50 miroM/kg) of CH203 3) HgCl and Na2SeO3 administered separately or concomitantly per os. Excretion of mercury through feces was the dominant clearance pathway in both groups. Selenium significantly decreased excretion of total and organic mercury in feces during the course of the study, but in the urine only on d 13. Selenium also significantly decreased the concentration of total mercury in major organs. The exception was brain on d 1, in which mercury levels were higher in the presence of selenium; however, on d 7 and 13 both cerebrum and cerebellum showed lower mercury levels as compared to the group treated with methylmercury alone. Selenium had no significant effect on the subcellular mercury distribution in the liver, kidney, and cerebrum, other than that which could be accounted for the whole organ uptake. The level of organic mercury in most of the analyzed organs was significantly decreased by the presence of selenium; however, relative proportions of inorganic to organic mercury remain unchanged. The single exception was kidney, where selenium markedly decreased the relative amount of inorganic mercury.

Animals↗
PubMed1977

[Studies of the tolerance and toxicity of Luzern-green-meal pellets after selenium fertilization].

In a feeding trial, rabbits allotted in 3 experimental groups were fed rations containing 2.09, 9.83 and 19.5 mg selenium/kg feed in the form of selenium-enriched alfalfa green meal pellets. The selenium enrichment was done by foliar application (spraying) of the 20--25 cm high plant stand with 2.5 kg SeO2 per hectare in watery solution. The control animals were given normal alfalfa green meal pellets of 0.16 ppm selenium content. Toxicity and lethality, tolerance limit and nutritive effect of the pellets were studied. Plant-assimilated selenium was found to be converted more efficiently by the animal organism than was selenium from inorganic compounds (higher retention rate, better gain in body weight and lower feed expenditure). Therefore, the selenium supply to farm animals should be improved by feeding crops that were given selenium dressings.

Animal Feed↗
PubMed2000

Effect of selenium and vitamin E content of the maternal diet on the antioxidant system of the yolk and the developing chick.

1. The effects of selenium and vitamin E supplementation of the maternal diet on their transfer to the egg yolk and tissues of the newly hatched chick and on the development of the antioxidant system in the chick liver in early postnatal life were investigated. 2. One hundred Cobb broiler breeder hens were divided into 10 equal groups and housed in pens at 25 weeks of age. Each hen received 1 of the treatment diets which included 0.2 or 0.4 mg/kg selenium, 40, 100, 200 mg/kg vitamin E or their combination. After 6 weeks, the hens were artificially inseminated once per week. From week 8, eggs were collected and placed in an incubator. After hatching, chicks from each group were reared (under standard commercial conditions) to 10 d of age. The chicks were fed on a standard starter commercial broiler diet. At the time of hatching, and at 5 and 10 days old, 4 chicks from each group were sacrificed and blood, liver and brain were collected for the subsequent biochemical analyses. 3. The inclusion of organic selenium or vitamin E in the commercial diet significantly increased their concentration in the egg and in the liver of 1-d-old chicks obtained from the eggs enriched with these substances. A positive effect of such dietary supplementation was seen at d 5 and d 10 of postnatal development. 4. There was a positive effect of selenium supplementation of the maternal diet on glutathione concentration in the liver of 1-d-old and 5-d-old chicks. A combination of a dietary selenium supplementation with high vitamin E doses further increased glutathione concentration in the liver. Dietary selenium supplementation significantly increased selenium-dependent glutathione peroxidase (Se-GSH-Px) activity in the liver of the 1-d-old and 5-d-old chicks and decreased liver susceptibility to peroxidation. 6. It is concluded that the nutritional status of the laying hen determines the efficiency of the antioxidant system throughout embryonic and early postnatal development of the offspring.

Animal Feed↗
PubMed2000

Selenium and interleukins in persons infected with human immunodeficiency virus type 1.

An important role for selenium in human immunodeficiency virus (HIV) disease has been proposed. Decreased selenium levels, as found in persons with HIV infection or AIDS, are sensitive markers of disease progression. Selenium deficiency, an independent predictor of mortality in both HIV-1-infected adults and children, is an essential micronutrient that is associated with an improvement of T cell function and reduced apoptosis in animal models. In addition, adequate selenium may enhance resistance to infections through modulation of interleukin (IL) production and subsequently the Th1/Th2 response. Selenium supplementation up-regulates IL-2 and increases activation, proliferation, differentiation, and programmed cell death of T helper cells. Moreover, selenium supplementation may down-regulate the abnormally high levels of IL-8 and tumor necrosis factor-alpha observed in HIV disease, which has been associated with neurologic damage, Kaposi's sarcoma, wasting syndrome, and increased viral replication. Together, these findings suggest a new mechanism through which selenium may affect HIV-1 disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Preischemic selenium status as a major determinant of myocardial infarct size in vivo in rats.

Prospective epidemiological studies have shown that the incidence of numerous cardiovascular pathologies is correlated with body selenium status. However, it remains unclear whether selenium status also influences the outcome of myocardial infarction. The aim of the present study was to test whether dietary selenium intake affects myocardial necrosis induced by transient regional ischemia in vivo in rats. For this purpose, male Wistar rats received either a high-selenium (High-Se: 1.5 mg of Se/kg) or a low-selenium (Low-Se: 0.05 mg of Se/kg) diet for 10 weeks. Animals were subjected to 30 min of myocardial ischemia induced by coronary artery ligation followed by 60 min of reperfusion. Pre- and postischemic blood samples were collected for glutathione (GSH and GSSG) determination and for glutathione peroxidase (GSH-Px) assessment. Our results show that high-selenium intake reduces myocardial infarct size (High-Se: 25.16 +/- 1.19% versus Low-Se: 36.51 +/- 4.14%, p < 0.05), preserves postischemic GSH/GSSG ratio (High-Se: 1.37 +/- 0.37 versus Low-Se: 0.47 +/- 0.10, p < 0.05), increases plasma GSH-Px activity, and improves postischemic mean arterial pressure. In conclusion, preischemic body selenium status is a major determinant of the outcome of myocardial ischemia in vivo in rats probably because it influences the cellular redox status.

Animals↗
PubMed2003

Dietary selenium intake affects cardiac susceptibility to ischaemia/reperfusion in male senescent rats.

BACKGROUND: cardiovascular ageing is associated with an increase in cardiac susceptibility to ischaemia and reperfusion. This has been suggested to be partly related to an increased sensitivity of the myocardium to the reactive oxygen species that are produced during post-ischaemic reperfusion. The aim of the present study was therefore to determine whether increasing cardiac glutathione peroxidase activity by a selenium-enriched diet could afford some protection against ischaemia and reperfusion to senescent rat hearts. METHODS: 22 months old male Wistar rats received either a high-selenium (1.5 mg Se/kg diet) or a low-selenium (0.05 mg Se/kg diet) diet for 10 weeks. At the end of the diet, hearts were submitted to ischaemia and reperfusion ex vivo and either fixed for semi-quantitative analysis of ultrastructural damage by electron microscopy or used for glutathione peroxidase activity assessment. RESULTS: high-selenium supply increased cardiac total, mitochondrial and cytosolic glutathione peroxidase activities. Moreover, this diet induced a significant improvement of cardiac post-ischaemic functional recovery. Finally, this preservation of cardiac function was associated with a significant limitation of ultrastructural alterations of sarcomeres and mitochondria. CONCLUSION: our high-selenium diet considerably limits the sensitivity of senescent rat hearts to ischaemia and reperfusion. This finding suggests that peroxides might play a key role in the increase in cardiac sensitivity to ischaemia and reperfusion during ageing. Together with the observation that selenium status decreases with age in humans, our results indicate that reinforcing selenium supply could improve the prognosis of cardiovascular diseases in old patients.

Aging↗
PubMed1990

The selenite-exchangeable metabolic pool in humans: a new concept for the assessment of selenium status.

An in vivo isotope-dilution approach is considered for assessment of selenium status in human subjects. The approach depends upon the dilution of a single dose of the stable isotope 74SeO3(2-) in the selenite-exchangeable metabolic pool. Data from six metabolic protocols, conducted with healthy North American males, are presented in order to analyze characteristics of this pool. Pool size (WSe-EMP) correlated positively with daily selenium intake in subjects consuming diets of known and variable selenium content. When subjects were given a selenium-adequate or -restricted diet for 30 d, WSe-EMP,7d decreased from 4.49 +/- 0.28 to 3.76 +/- 0.22 mg (p less than 0.05). The corresponding 24-h urinary selenium concentration dropped from 0.556 +/- 0.035 to 0.341 +/- 0.058 mumol/d (means +/- 1 SEM). Route of administration (iv vs po) had no apparent effect on WSe-EMP. In subjects of similar selenium status, the WSe-EMP was reproducible within the expected uncertainties of the method. This approach may be suitable for assessment of selenium status for a wide range of chronic intakes.

Adult↗
PubMed1991

Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast.

The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.84 +/- 0.26 to 1.55 +/- 0.33 mumol/L (mean +/- SD) after 2 mo and the values plateaued thereafter. The mean response of lymphocytes to mitogens in elderly subjects tended to be lower than responses in healthy adults, although responses remained within the 5-95% confidence-interval limit for healthy adults. During selenium supplementation the proliferative response to pokeweed mitogen increased significantly (+79% of baseline concentrations after 4 mo, P less than 0.01) and reached the upper limit of the usual range for adults after 6 mo (+138%, P less than 0.001). In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans.

Aged↗
PubMed1992

Selenium status in patients with Crohn's disease.

Twenty-seven of 66 patients with Crohn's disease had reduced concentrations of selenium and glutathione peroxidase in plasma and erythrocytes. When the patients were subgrouped according to the length of resected small bowel, a significant reduction of selenium and glutathione peroxidase in both plasma and erythrocytes was only found in patients with a resection > 200 cm. A highly significant correlation between selenium and glutathione peroxidase was found in plasma (r = 0.81) as well as in erythrocytes (r = 0.62), but no correlation was observed in the control group. A statistically significant correlation was also found between plasma selenium and the Harvey-Bradshaw score (r = -0.44), body mass index (wt/ht2) (r = 0.47), and plasma albumin (r = 0.29). Patients with a small-bowel resection > 200 cm appear to be at risk of developing severe selenium deficiency. These patients should have their selenium status monitored and probably receive selenium supplementation.

Adult↗