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Effect of selenium supplementation on the distribution of selenium in plasma proteins of healthy subjects.

The influence of an increased intake of selenium on the distribution of this element among plasma proteins was studied. 200 micrograms of yeast selenium was given to healthy subjects daily for 8 weeks, and then the subjects refrained from selenium supplementation for 16 weeks. Plasma selenium increased almost two-fold during supplementation, and most of the increase occurred during the first 4-week-period. Plasma glutathione peroxidase activity increased only marginally. At all times studied, most of the selenium in plasma was located in proteins, migrating close to immunoglobulin G on gel filtration. The selenium content of this fraction was only moderately increased after supplementation for 8 weeks, and instead more marked increases occurred in the regions for high-molecular-weight proteins and albumin. This change implied that the distribution of selenium approached that of total protein, and we therefore conclude that most of the increase in plasma selenium occurred via unspecific incorporation of selenium into a wide variety of proteins. Sixteen weeks after the end of supplementation the selenium distribution had essentially returned to that before supplementation.

Adult↗

Effects of intramuscular injections of selenium and vitamin E on selenium-vitamin E deficiency in young pigs.

Effects of intramuscular injections of selenium and vitamin E on lesions in pigs with selenium-vitamin E deficiency syndrome were determined in 2 factorial experiments, using a total 69 pigs. The pigs were fed a selenium-vitamin E deficient, 22.3% protein ration, supplemented with methionine, minerals, and vitamins. Weekly intramuscular injections of isotonic saline solution, vitamin E, selenium, or vitamin E and selenium were given to the respective treatment groups. Selenium-vitamin E deficiency lesions occurred only in pigs that were given saline injections. Weekly intramuscular injections of either selenium (as selenous acid buffered to pH (7.3) at the rate of 0.05 mg/kg of body weight or vitamin E at the rate of 20 IU/kg of body weight or the combination of selenium and vitamin E prevented cardiac and skeletal myodegeneration, hepatic necrosis, and death. Significant increases of serum aspartate aminotransferase activity values were noted in pigs with liver, heart, or skeletal muscle lesions, but these increases were not correlated with the extent of the lesions. Vascular lesions, epicardial and endocardial hemorrhages, and yellow discoloration of body fat were not features of this experimentally induced disease. These lesions may be related to factors other than the deficiency of selenium, vitamin E, or selenium and vitamin E in rations previously used in reported studies.

Animals↗

Effects of water supplementation with selenium and vitamin E on growth performance and blood selenium and serum vitamin E concentrations in weanling pigs.

OBJECTIVE: To determine effects of supplementation of drinking water with selenium and vitamin E on blood selenium and serum vitamin E concentrations, growth performance, and water intake of pigs. DESIGN: Prospective controlled study. ANIMALS: 228 weanling pigs. PROCEDURE: In experiments 1 and 2, pigs were given drinking water supplemented with selenium and vitamin E, and blood selenium and serum vitamin E concentrations were measured. In experiment 3, growth performance and water intake were measured in pigs that received supplemented water for 2 or 5 weeks and in control pigs. RESULTS: In experiment 1, blood selenium concentrations were significantly increased after 7 days of supplementation, and serum vitamin E concentrations were significantly increased after 1 and 7 days of supplementation, compared with baseline concentrations. In experiment 2, blood selenium concentrations were not significantly different between treated and control pigs, and serum vitamin E concentrations were significantly increased on day 7. In experiment 3, gain-to-feed ratios were significantly higher for pigs supplemented with selenium and vitamin E for 5 weeks, but other differences were not detected. CLINICAL IMPLICATIONS: Supplementation of drinking water with selenium and vitamin E may improve the selenium and vitamin E status of weanling pigs by increasing selenium and vitamin E intake.

Analysis of Variance↗

Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite, and selenate.

The mean dietary selenium intake in Finland increased from 40 to 100 micrograms/d in 1987 because of the addition in 1985 of selenium to fertilizers. A selenium-supplementation study was performed in 1987 on the same men as were followed in a 1981 study that had a similar design (200 micrograms Se/d). Selenite and selenate, but not selenium yeast increased platelet glutathione peroxidase (GSHPx) activity by 30% compared with placebo, much less than the 70% found in the previous study. Selenium yeast and selenite increased plasma selenium after 11 wk from 1.39 mumol/L to peak values of 2.15 and 1.58 mumol/L, respectively. Only yeast selenium was incorporated into red cells. From a regression plot based on present and literature data, it was estimated that the plasma selenium concentration needed to achieve maximal platelet GSHPx activity was 1.25-1.45 mumol/L. At the present selenium intake in Finland, 100 micrograms/d, GSHPx activity is saturated in plasma and red cells and almost saturated in platelets.

Analysis of Variance↗

Significance of selenium-labeled proteins for selenium's chemopreventive functions.

A 58 kDa selenium-labeled protein purified from mouse mammary epithelial cells (MMEC) was used to examine whether selenium modulates protein synthesis or is just a marker for cellular selenium status. The protein was isolated using Sephadex G150 gel filtration and DEAE-Sephadex A50 ion-exchange chromatography. It was further analysed using 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and was found as a single spot with a pI of 4.6. The immunoreactivity with anti-58 kDa antiserum and the 75Se signal co-localized on a single 58 kDa protein band on both 1D- and 2D-PAGE. Partial amino acid analysis of the peptide showed homology with the thiol protein disulfide oxidoreductase (TPDO). Varying the selenium concentration in culture medium did not affect the protein content or the immunoreactivity of the 58 kDa protein. Additionally, selenium did not seem to regulate the activity of TPDO in TM6 cells. The glutathione peroxidase activity of TM6 cells, taken as the internal positive control, was enhanced with the increase in selenium concentration in the medium. The results suggest that selenium is attached to the 58 kDa protein, but does not regulate either its protein synthesis or its functional activity. We conclude that selenium labeling of the 58 kDa protein reflects the cellular selenium status but probably is not involved in its chemopreventive ability.

Amino Acid Sequence↗

Iodothyronine deiodinase activity in methionine-deficient rats fed selenium-deficient or selenium-sufficient diets.

We examined the effect of methionine deficiency on iodothyronine 5'-deiodinase activity in selenium-deficient rats or selenium-sufficient rats fed sodium selenate or selenomethionine. Forty-two weanling male Wistar rats were divided into six groups and pair fed the respective purified L-amino acid-based diets for 4 wk. L-methionine concentrations in the diet were 8.0 g/kg for sufficient rats, and 2.0 g/kg for deficient rats. Selenium concentrations in the diet were 0.5 mg/kg (as sodium selenate or selenomethionine) for selenium-sufficient rats and less than 0.005 mg/kg for selenium-deficient rats. Type I 5'-deiodinase activities were significantly lower in liver and higher in kidney of methionine-deficient rats than in those of methionine-sufficient rats fed either the selenium-sufficient or the selenium-deficient diets. The type I 5'-deiodinase activity in brain was significantly lower in the methionine-deficient rats than in the methionine-sufficient rats fed the selenium-deficient diet. Type II 5'-deiodinase activity in brain was significantly higher in the methionine-deficient rats than in the methionine-sufficient rats fed selenium-sufficient diet as sodium selenate. Both thyroxine and 3,3',5-triiodothyronine concentrations in plasma were significantly higher in the methionine-deficient rats than in the methionine-sufficient rats. It is suggested that the methionine deficiency affects the 5'-deiodinase activity and thyroid hormones level in the rats.

Animals↗

Selenium and cancer: effects of selenium and of the diet on the genesis of spontaneous mammary tumors in virgin inbred female C3H/St mice.

Inbred female C3H/St mice exhibit the normal incidence of spontaneous mammary adenocarcinoma of 80--100% if they are maintained on a standard commercial laboratory diet containing 0.15 ppm of selenium with meat and dried skimmed milk as major sources of protein. The tumor incidence drops to 42% if animals of the same strain are kept on a diet containing 0.45 ppm of selenium, with fishmeal as the main source of protein. The tumor incidence declines further to 25, 19 and 10% if the animals in addition receive 0.1, 0.5, and 1.0 ppm of selenium in the drinking water. Selenium supplementation at these levels has no noticable adverse effects on weight-grains and survival of the mice. Selenium supplmented groups of animals also remained tumor-free for longer periods than the unsupplemented controls. The results of this study indicate that a diet rich in seafoods and cereals provides more selenium and may in turn lower the probability of cancer development. Reference is made to the average human diet in the U.S.A., which only contains 0.07--0.15 ppm of selenium due to the comparatively low consumption of cereals and seafoods. An equivalent mouse diet would not have any cancer-protecting effect in the C3H/St mice of our study. Australian workers have reported significantly lower tumor incidence in a different strain of C3H mice if it was kept in Australia rather than in the U.S.A. We have found that the Australian feed contained three times more selenium than that employed in the U.S.A. and propose that this difference in selenium content was primarily responsible for these previous observations.

Animals↗

Sulfur--selenium studies in sheep. II. Effect of a dietary sulfur deficiency on selenium and sulfur metabolism in sheep fed varying levels of selenomethionine.

The effect of a sulfur deficiency on the metabolism of selenium and sulfur was investigated in eight merino wethers. The sheep were fed high-sulfur (2 g S/kg) or low-sulfur (0.5 g S/kg) diets for two periods of 35 days each, and received selenium as selenomethionine at dietary concentrations of 0.02, 0.06, 0.09 and 0.67 mg Se/kg. Sheep fed the low-sulfur diet had reduced feed intake, reduced nitrogen, sulfur and selenium balance, but elevated plasma and wool selenium concentrations. Selenium concentrations in organs and tissues of slaughtered animals paralleled the selenium intake of the animal, with the renal cortex containing the highest concentration and bone the lowest. The effect of the 0.5 g S/kg diet on feed intake is in contrast with the results from the previous experiment (White and Somers 1977) using 0.7 g S/kg. It is this difference in fed intake which was responsible for many of the effects on selenium metabolism observed in this experiment. Once the feed intake effects are accounted for, the implications for sulfur--selenium interactions remain as before, i.e. more selenium is incorporated into wool and plasma protein when dietary sulfur is limiting than when it is not.

Animals↗

Increased plasma and erythrocyte selenium concentrations but decreased erythrocyte glutathione peroxidase activity after selenium supplementation in children with Down syndrome.

An investigation was made of the activity of glutathione peroxidase (GSH-Px) in erythrocytes and the levels of selenium in plasma and erythrocytes before, during and after selenium supplementation in children with Down syndrome (DS). This subject is of interest since it has been suggested that selenium supplementation could enhance the GSH-Px activity in erythrocytes, probably leading to improved protection against oxygen radicals, which might cause damage by lipid peroxidation, especially in the brain. Forty-eight children with DS were treated with selenium-rich yeast tablets (10 micrograms/kg body weight/day) for 6 months. The supplementation was well tolerated and no side effects were observed. Selenium supplementation resulted in increased concentrations of selenium both in plasma and erythrocytes, but decreased GSH-Px-activity in erythrocytes. Plasma and erythrocyte selenium levels but almost regained the initial values 12 months after termination of the supplementation. Erythrocyte GSH-Px activity, on the other hand, remained reduced and did not return to the presupplementation levels. Until we gain more knowledge about the biological functions of selenium in man and the role of oxygen metabolism in the development of presenile dementia in DS, universal selenium supplementation in DS patients cannot be recommended.

Adolescent↗

The effect of selenium supplementation on skeletal and cardiac muscle in selenium-depleted patients.

BACKGROUND: The purpose of the present study was to evaluate the effect of sodium selenite on skeletal and cardiac muscular function in patients with severe Se deficiency. METHODS: Skeletal and cardiac muscular function was investigated in 10 selenium depleted patients on long-term home parenteral nutrition because of short bowel syndrome. The following examinations were applied: Skeletal muscle biopsy, muscular force test (Kin-Com dynamometer test), electromyography (EMG) and radionuclide ventriculography. The patients were blindly randomized to intravenous supplementation with selenium 200 micrograms 5 to 7 times per week or placebo for 4 months. Hereafter the examinations were repeated. The patients randomized to placebo received selenium in an open study for a further 4 months and hereafter their skeletal and cardiac function was reevaluated. RESULTS: Plasma selenium increased to normal levels from median .21 mumol/l (range 0-.69) to 1.25 mumol/l (range .9-2.27) following selenium repletion. The muscle biopsies showed only minor abnormalities. The only change after selenium supplementation was a small but statistically significant increase of the mean diameter of fiber type 1. The muscle strength of the quadriceps muscle was unchanged after selenium substitution. EMG did not reveal signs of myopathy. The cardiac function was normal and remained unchanged. CONCLUSION: Despite severe selenium depletion ten patients on long term home parenteral nutrition had normal cardiac function, and no clinically significant signs of skeletal myopathy. The only change after selenium supplementation was a small but statistically significant increase of the mean diameter of muscle fiber type 1.

Adult↗

Effect of selenium intake on selenium utilization by the nonlactating dairy cow.

Total collection digestion trials were used to study selenium absorption and retention as related to selenium intake in nonlactating dairy cows. Relationship between selenium absorption and retention was linear over selenium intakes from 400 to 3100 micrograms/day. Regression analysis showed partial selenium absorption of 51% over total range of intake and 41% retention of dietary selenium intake. Also, negative selenium balances could occur when nonlactating cows are fed selenium-deficient diets without a supplemental source of selenium.

Animals↗

[The selenium content in the blood of newborn sheep and goats--equally contributing to the effect of supplemental oral selenium as a prophylaxis].

The article is based on the analysis of selenium concentration in blood plasma of 9 goats and their kids (n = 17), from two different places, as well as of 12 sheep and their lambs (n = 19) from several flocks. The selenium concentration was measured using ASS. In addition, the activity of CK was determined enzymatically. There was a low plasma selenium level in lambs and goat kids immediately post-natal depending on the selenium state of the mothers. After application of vitamin E and selenium to a group of lambs their selenium levels increased remarkably over 24 hours. Ten days later the average selenium concentration in the plasma of those animals that had been treated was three times as high as that of the control group. It was shown that the absorption of vitamin E and selenium when given orally to newborn lambs is comparable with the absorption after parenteral application, and that a significant increase of the plasma selenium level is attainable by oral application.

Absorption↗

Annual variation of serum selenium in patients with gynaecological cancer during 1978-1983 in Finland, a low selenium area.

To explore the relationship between selenium deficiency in cancer and nutritional factors, we measured the serum concentrations of selenium in 1978-1983 in patients with gynaecological cancer (N = 277) and correlated these with the estimated daily intake of selenium, which varies in Finland depending on the proportion of selenium-rich imported grain. The selenium concentration increased significantly from 1978-1979 to 1982 in the series of all cancer patients (p less than 0.001) and separately in cases of cervical (p less than 0.001) and endometrial cancer (p less than 0.02), parallel to the increased daily intake of selenium. The serum level of selenium decreased in 1983, when the import of selenium-rich grain was reduced. Low serum selenium in cancer patients thus seems to be mainly dependent on dietary factors.

Aged↗

Serum selenium, glutathione peroxidase activity and high-density lipoprotein cholesterol--effect of selenium supplementation.

In a prospective study a low serum selenium level was associated with an increased risk of coronary death and myocardial infarction (1). This study examined the relationship of serum selenium concentration with serum glutathione peroxidase activity (GSH-Px) and lipids connected with coronary atherogenesis. Serum selenium levels in 26 healthy subjects were positively correlated with GSH-Px activities and high-density lipoprotein cholesterol concentrations. Selenium supplementation increased serum selenium level and the GSH-Px activity in a double-blind evaluation. The high-density lipoprotein cholesterol/cholesterol ratio increased during selenium supplementation in a group excluding subjects with a low cholesterol. The results suggest a link running from low serum selenium to reduced high-density lipoprotein cholesterol, and further to high coronary risk. Selenium supplementation may in subjects with low selenium reduce the the risk of coronary heart disease.

Adult↗

[Effect of dl-alpha-tocopherol on incorporation of selenium in "selenium-indicating" organs and on glutathione peroxidase activity in rat and rabbit erythrocytes following application of therapeutic doses of sodium selenite].

An explanation of the functions of both vitamin E and selenium in metabolism and an account of the correlations between them is followed by reference to the results obtained by the authors of this paper from studies into the effects of dl-alpha-tocopherol on selenium levels in the M. longissimus dorsi, blood, and liver as well as on the activity of glutathione-peroxidase (EC 1.11.1.9) in erythrocytes of rabbit and rat, following application of therapeutic doses of selenium (0.5 mg/kg live weight). In both species selenium application increased the glutathione-peroxidase activity in erythrocytes. Vitamin E had no additional effect. Application of selenium was followed by rise in intraorganic selenium concentrations. In rabbit, the effect of vitamin T on intraorganic distribution of selenium caused an increased of the selenium level in the liver, but not in the muscles. No vitamin E effect was recordable in the rat. The findings are discussed, with conclusions being suggested for the treatment of metabolic disorders in the context of selenium and vitamin E and for non-invasive liver therapy.

Animals↗

Effect of double-blind crossover selenium supplementation on biological indices of selenium status in cystic fibrosis patients.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.

Adolescent↗

Selenium supplementation affects the retention of stable isotopes of selenium in human subjects consuming diets low in selenium.

Twenty-nine women and fifteen men from an area of low Se intake (South Island of New Zealand) consumed 100 micrograms stable 74Se, as selenate given in water after an overnight fast, and blood was collected for 3 weeks. They were then divided into five groups and supplemented with 0, 10, 20, 30 and 40 micrograms Se/d (as selenomethionine) for 5 months. After 5 months, they received a second dose of 74Se identical to the first. Supplementation significantly altered retention of 74Se in the plasma, but not in the erythrocytes or platelets. Subjects receiving the placebo retained the greatest amount, and subjects receiving 30 micrograms supplemental Se/d retained the least 74Se. Supplementation resulted in relatively more isotope being retained in a medium molecular mass protein considered to be albumin, and relatively less in another fraction considered to be selenoprotein P. The lack of many observed changes in retention of stable Se, and the shift in retention among the plasma proteins, suggests that supplemental Se was not being used to replete critical pools of Se, probably because of adaptation to low Se intake.

Adaptation, Physiological↗