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Dose-dependent distribution of injected selenium in rat blood. Effect of previous selenium intake in drinking water.

The effect of an administered dose of 75Se-selenite and a previously increased selenium intake in drinking water (0.1 mg/l) on the distribution of injected selenium in rat blood was studied. In a dose range of 0.01-1.6 mg Se/kg body weight the ratio of injected selenium in blood plasma and in blood cells decreased from 3.20 in rats with increased selenium intake and 4.60 in rats without this intake, to 0.13 and 0.10, respectively. After injection of high selenite doses, 85-88% of the selenium present in the blood was localized in blood cells irrespective of increased selenium intake by drinking water. Possible relationship between accumulation of selenium in blood cells and its toxic effect in the organism is discussed. Previously increased intake of selenium had no effect on the levels of selenium in blood cells but affected significantly its plasma levels. The results indicate that the previously increased selenium intake in drinking water increases the capacity of the plasma for selenium injected in the form of selenite.

Animals↗

Selenium administration does not cause thyroid insufficiency in subjects with mild iodine deficiency and sufficient selenium intake.

Selenium is a trace element essential for the activity of type I 5'-deiodinase which converts thyroxine (T4) to 3,5,3'-triiodothyronine (T3). In iodine deficient hypothyroid children at low selenium dietary intake the supplementation of selenium induced a significant decrement of serum FT4 and T4 concentrations and an increase of serum TSH concentrations. Since in western countries selenium tablets begin to be largely consumed as a diet integrator, we have administered 100 micrograms/day of selenium as selenium methionine to 8 euthyroid female subjects with a positive iodine-perchlorate discharge test who had a previous episode of subacute or postpartum thyroiditis. We have studied subjects with positive iodine-perchlorate discharge test since the test indicates the existence of a subtle defect of thyroid hormone synthesis and therefore these subjects are prone to develop thyroid dysfunction. In contrast to previous findings in hypothyroid children at low iodine and selenium dietary intake, the supplementation of selenium did not decompensate thyroid hormone synthesis of euthyroid subjects with reduced thyroid iodine organification. The lack of any effect of selenium on thyroid hormone synthesis even in subjects with subtle thyroid hormone synthesis defect may be due to the fact that these subjects had a sufficient selenium dietary intake before selenium supplementation and an only marginally reduced dietary iodine intake.

Adult↗

Effects of selenium supplementation on blood and urine selenium levels and liver function in patients with primary biliary cirrhosis.

To study the mechanism of the reduced serum selenium concentration in patients with liver damage we administered 200 micrograms (2.53 mumol) selenium daily as selenium-rich yeast to 8 patients with primary biliary cirrhosis and 8 healthy controls over 16 weeks. Initially selenium concentrations in serum were 24% lower (P less than 0.001) in patients than controls. During supplementation serum selenium levels increased in both groups but the difference between them persisted. Throughout the study whole blood selenium levels and glutathione peroxidase activities were also somewhat lower (P = NS) in patients than controls. Selenium supplementation had no effect on whole blood glutathione peroxidase activities in either group. The basal 24 h urinary excretion of selenium was similar in both groups but was increased more by supplementation in patients than controls. Selenium administration did not influence the liver function of the patients. We conclude that impaired hepatic production of selenium-containing serum compounds is the most likely explanation for the reduced serum selenium concentration in patients with primary biliary cirrhosis.

Adult↗

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula.

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.

Enteral Nutrition↗

Efficacy of cancer prevention by high-selenium garlic is primarily dependent on the action of selenium.

We reported previously that garlic cultivated with selenite fertilization showed powerful chemopreventive activity in the rat dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model (Carcinogenesis 15, 573-576, 1994). In order to ascertain that the efficacy of the high-selenium garlic in cancer protection is primarily dependent on the action of selenium we compared the effects of two batches of garlic powder with marked differences in their level of selenium enrichment, 112 or 1355 p.p.m. Se dry weight. Both products were added to the diet to achieve the same final concentration of 2 p.p.m. Se. The supplementation protocol was designed to evaluate the efficacy during either the initiation phase or post-initiation phase of DMBA mammary carcinogenesis. Significant tumor reduction was observed with either treatment protocol. Furthermore, the magnitude tumor suppression, as well as the extent of DMBA-DNA adduct inhibition, were very similar with the two batches of garlic, even though the amounts of garlic in the diet varied considerably between them (1.8% for the 112 p.p.m. Se garlic versus 0.15% for the 1355 p.p.m. Se garlic). This suggests that the anti-cancer activity of the high-selenium garlic was likely to be accounted for by the effect of selenium, rather than the effect of garlic per se. A continuous feeding of the high-selenium garlic produced a modest increase in total selenium in various tissues. In general the profile of selenium accumulation was comparable in rats ingesting either the 112 or the 1355 p.p.m. Se garlic. Thus, based on the results of several biological responses, it appears that the ability of the high-selenium garlic to protect against tumorigenesis is primarily dependent on increased intake of selenium provided by the vegetable. Future research will be focused on the chemical form of selenium in the garlic.

9,10-Dimethyl-1,2-benzanthracene↗

Altered selenium-binding protein levels associated with selenium resistance.

Our previous studies have sought to elucidate the mechanism by which selenium inhibits cell growth since the mechanisms involved may be relevant to the chemopreventive properties of selenium. In a previous report, we described the isolation of a selenium-resistant cell line, B19, from a selenium-sensitive parental cell line, C57. In this report we identify biochemical changes that may be responsible for conferring selenium resistance. Altered selenium uptake and intracellular glutathione concentrations were eliminated as possible modes of resistance since these two parameters were similar between the two cell lines. However, when the selenium-containing protein complements of the two cell lines were compared by labelling with [75Se]selenite, both increases and decreases in a number of selenium-labelling proteins were found in the B19 cells. The most striking differences were the presence of two 72 kDa selenium-labelling proteins in B19 cells which could not be detected in C57 cells. The levels of a number of mRNAs encoding antioxidant or detoxification enzymes were also compared between the two cell lines but only minor changes were found. This work suggests that further analysis of the 72 kDa selenium-labelling proteins may reveal insights into the mechanisms of growth inhibition by selenium.

Animals↗

Selenium status and the effect of organic and inorganic selenium supplementation in a group of elderly people in Denmark.

The selenium status of 57 elderly people (> or = 65 years) has been investigated on the basis of selenium concentration in serum, whole blood and erythrocytes and on the basis of the activity of the selenium-dependent enzyme glutathione peroxidase (GSH-px) in erythrocytes and plasma. Thirty-six elderly subjects participated in a 4-month trial of supplementation: 12 subjects were supplemented with 125 micrograms organic selenium, 12 subjects were supplemented with 125 micrograms inorganic selenium and 12 subjects participated as controls. The results showed that the selenium status of the elderly people was not significantly lower than that of younger people (p > 0.05). The effect of organic and inorganic selenium on the activity of GSH-px in plasma and erythrocytes showed a nearly identical increase (25-35%) during the period of supplementation. The effect of inorganic selenium supplementation caused a 30% increase in selenium concentration in plasma and erythrocytes which stabilized after 4 weeks. The effect of organic selenium supplementation on selenium concentration in plasma and erythrocytes showed an increase of up to 100% and 120% during the period of supplementation.

Age Factors↗

Transfer of selenium from blood to milk in goats and noninterference of copper with selenium metabolism.

The mechanism of selenium secretion by the mammary gland and effects of dietary copper and selenium metabolism on selenium in milk were investigated. Radioactive sodium selective selenite was injected into the jugular vein of lactating goats fed concentrates containing 15 or 115 ppm copper. Blood and milk samples were collected hourly for 8 h and daily for 1 wk. Whole blood, plasma, whole milk, and casein, whey, and cream fractions of milk were counted for selenium-75. No significant differences due to dietary copper were seen. The selenium-75 was primarily associated with the casein in milk. The association of selenium with the whey fraction was greater for early periods than later and varied between animals. The specific activity based on protein content was greater in casein than in whey. Peak selenium-75 in whole milk occurred 2 h after the peak in plasma. On day 7 following selenium-75 dosing, kidney had the highest specific activity, and liver was slightly higher than mammary tissue. All subcellular organelle fractions of liver, kidney, and mammary tissue by homogenization and differential centrifugation contained significant selenium-75. Selenium normally is secreted from the mammary secretory cell in combination with protein through the secretory vesicles, metabolism of selenite prior to milk secretion is important, and copper does not interfere with normal metabolism of selenium.

Animals↗

The form of selenium determines the response to supplementation in a selenium replete population.

In an ongoing study of selenium bioavailability, effects of supplementation with organic and inorganic forms of selenium were investigated in healthy, Norwegian women, aged 23-50 years. In phase I of the study, 58 women received 200 micrograms selenium per day either as selenite or selenium-rich pea flour for 3 months. The selenium tablets were taken together with placebo or ascorbic acid in a double blind design. Initial blood and serum selenium concentrations were 153 +/- 15 micrograms/l and 117 +/- 12 micrograms/l, respectively. These are average values for Norwegians. Indications of increased blood levels were seen in all groups, but the rise reached significance only for the subgroup receiving selenite and ascorbic acid, 14 micrograms/l, P less than 0.05. On the other hand, selenium analysis of 72-h urine samples confirmed that at an average 50 per cent of the selenium supplements had been absorbed. In phase II of the study, 28 of the participants continued for another 5 weeks, still on 200 micrograms Se per day, but this time consuming commercially available preparations. Of four preparations that were tested, two consisted of yeast Se. Only one of these produced a significant rise in blood and serum selenium levels, 60 and 55 micrograms/l respectively. Blood glutathione peroxidase values were not affected by any supplementation. The study demonstrates that different forms of organic selenium elicit widely different responses when administered to a relatively selenium-replete population, and that the explanation for this must be sought at the metabolic level.

Adult↗

Effect of selenium supplementation to fertilizers on the selenium status of the population in different parts of Finland.

Concentrations of selenium in the soil are very low in most regions in Finland, which explains the low selenium contents of agricultural plants and the low dietary intake of selenium. The poor selenium status of the population in Finland has been considered a possible risk to public health. In 1984, it was decided to increase the selenium intake by adding selenate to common agricultural fertilizers. In this study, the selenium concentrations of whole blood and plasma, as well as erythrocyte glutathione peroxidase activities, were measured in blood samples from four different localities in Finland, in 1984 and 1986, before and during the agricultural selenium supplementation. A low blood level of selenium in the inhabitants of central Finland was demonstrated in 1984. The selenium level of people from the south-west archipelago was a little higher, and that from the northern part of Finland considerably higher than the level in the rest of the country. By 1986, differences between these localities had almost disappeared, and most levels had increased. Plasma selenium concentrations were lower than those in whole blood samples; the concentrations showed a significant correlation. The glutathione peroxidase activities were at the same level in all four localities in 1984. By 1986, they had all increased to a slightly higher level. A weak correlation was found between erythrocyte glutathione peroxidase activity and blood selenium level.

Adult↗

Differences in the effects of selenite and biological selenium on the chemical form and distribution of mercury after the simultaneous administration of HgCl2 and selenium to rats.

The interaction was compared between inorganic (HgCl2) mercury and selenite (Na2SeO3) vs. the interaction between inorganic mercury and biological selenium (a freeze-dried preparation of liver from rats treated with selenite). Organ concentrations of selenium were always significantly lower after biological selenium than after selenite. Biological selenium affected the organ distribution of inorganic mercury differently than selenite. Furthermore, the speciation of mercury was affected by this form of selenium. A mercury-selenide compound (presumably HgSe) accounted for a greater proportion of total mercury in tissues after selenite than after a dose of biological selenium. Administration of selenomethionine had a similar effect on the speciation of mercury to that seen after biological selenium. As the forms of selenium in selenomethionine or selenium deposited in the liver are most likely nearer than selenite to selenium present in food, our results suggest that, as far as the reaction of mercury with selenide is concerned, experiments with selenite overestimate the protective effect of dietary selenium against inorganic mercury and possibly against methylmercury.

Animals↗

Glutathione peroxidase activities during selenium depletion of adult female rats and during selenium repletion of their offspring.

The main purpose of the present investigation was to produce young rats with severe selenium deficiency, but with no clinical signs of this deficiency, and to examine their liver and red blood cell (RBC) glutathione peroxidase activities during selenium repletion. To achieve this goal, female breeders were fed a selenium-deficient diet beginning 2 weeks before mating. The liver glutathione peroxidase activity of the dams was significantly lower than the activity of comparable nonpregnant females after 5 and 10 weeks of selenium depletion. This difference arose exclusively during the period of pregnancy. In contrast, the RBC glutathione peroxidase activity was significantly increased during this period. Only traces of liver enzyme activity were found in the offspring, and the RBC enzyme activity was only 2% of that of the selenium-repleted controls. Body weight was retarded in the male offspring. However, no severe signs of clinical selenium deficiency were observed. The glutathione peroxidase activity in the liver and RBCs of the offspring was determined after 0, 2, 4, 7, 14, and approximately 40 days of selenium repletion. The liver enzyme activity increased faster in females than in males, while the opposite was found for the RBCs. After 14 days of selenium repletion, the glutathione peroxidase activity of the liver was essentially restored, and the RBC enzyme activity was about half that of the control values. This type of rat may prove useful in studies in which young selenium-deficient rats are preferable, as well as in studies of selenium functions that might not be directly related to the role of selenium in glutathione peroxidase.

Journal Article↗

The effect of copper on the response of lambs to selenium supplementation when grazing a selenium deficient pasture.

Two trials were undertaken with lambs grazing selenium deficient pasture to determine if copper would enhance liveweight and fleece-weight responses to selenium supplementation. In the first trial, lambs given selenium or selenium plus copper gained significantly more weight and had higher fleece-weights after 260 days than did control lambs or lambs given copper alone. Copper given alone or together with selenium had no significant effect on liveweight or fleece-weight when compared with control lambs and lambs that were given selenium alone respectively. This finding was confirmed in a second trial when growth and fleece-weights of selenium and selenium plus copper treated lambs were compared and no significant differences found. In both trials copper significantly raised liver copper levels. In selenium supplemented but not in selenium deficient sheep, copper significantly increased blood selenium levels.

Journal Article↗

Exclusion of selenium from proteins of selenium-tolerant astragalus species.

Protein fractions from three selenium-tolerant and three selenium-sensitive Astragalus species, grown in the presence of [(75)Se]selenate, were analyzed for their selenium content. Though tolerant species are known to accumulate considerably more selenium than do sensitive plants, protein fractions from the three selenium accumulators were found to contain significantly less selenium (0.46 to 0.57 picomoles selenium per milligram protein) than did protein fractions from the three nonaccumulators (4.17 to 5.02 picomoles selenium per milligram protein). Under similar conditions, seedlings of Vigna radiata (L.) Wilczek had taken up selenium (6.31 picomoles selenium per milligram protein) at levels comparable to those observed in the proteins of the nonaccumulator Astragali. These results establish that the ability to tolerate and to circumvent the toxic effects of selenium, characteristic of the accumulator species of Astragalus, is associated with a reduced incorporation of this element into protein.

Journal Article↗

Direct detection of potential selenium delivery proteins by using an Escherichia coli strain unable to incorporate selenium from selenite into proteins.

Selenium can be metabolized for protein synthesis by two major pathways in vivo. In a specific pathway it can be inserted into polypeptide chains as the amino acid selenocysteine, as directed by the UGA codon. Alternatively, selenium can be substituted for sulfur to generate the free amino acids selenocysteine and selenomethionine, and these are incorporated nonspecifically into proteins in place of cysteine and methionine, respectively. A mutant strain of Escherichia coli was constructed that is deficient in utilization of inorganic selenium for both specific and nonspecific pathways of selenoprotein synthesis. Disruption of the cysK gene prevented synthesis of free cysteine and selenocysteine from inorganic S and Se precursors. Inactivation of the selD gene prevented synthesis of selenophosphate, the reactive selenium donor, required for the specific incorporation pathway. As expected, the double mutant strain, RL165 Delta selD, when grown anaerobically in LB + glucose medium containing (75)SeO(3)(2-), failed to synthesize selenium-dependent formate dehydrogenase H and seleno-tRNAs. However, it incorporated 24% as much selenium as the wild-type strain. Selenium in the deficient strain was bound to five different proteins. A 39-kDa species was identified as glyceraldehyde-3-phosphate dehydrogenase. It is possible that selenium was bound as a perselenide derivative to the reactive cysteine residue of this enzyme. A 28-kDa protein identified as deoxyribose phosphate aldolase also contained bound selenium. These (75)Se-labeled proteins may have alternate roles as selenium delivery proteins.

Aldehyde-Lyases↗

Effect of selenium supplementation on platelet selenium, glutathione peroxidase, and aggregation.

The selenium content of platelets is extremely high. About half of this selenium originates from irreversible incorporation by bone marrow precursor cells, which satisfy their need for selenium even under conditions of marked selenium deficiency. In order to study the effect of increased dietary selenium supply on the concentration of selenium, glutathione peroxidase (GSH-Px-) activity, and aggregability of platelets, normal healthy subjects were supplemented with 300 micrograms of selenium as Se-rich yeast/d for 3 mo. No significant effect of Se supplementation on platelet Se and GSH-Px were observed, whereas erythrocytes accumulated Se without reaching saturation. Although platelet aggregability was variable during the period of observation, this was traced back to factors other than selenium, including environmental temperature. This study demonstrates that the selenium concentration of platelets is subject to tight physiological control also at high dietary selenium intakes.

Adult↗

Determination of total selenium and selenium distribution in the milk phases in commercial cow's milk by HG-AAS.

A procedure has been developed for determining the selenium in cow's milk using hydride generation-atomic absorption spectrometry (HG-AAS) following microwave-assisted acid digestion. The selenium distributions in milk whey, fat and micellar casein phases were studied after separating the different phases by ultracentrifugation and determining the selenium in all of them. The detection limits obtained by HG-AAS for the whole milk, milk whey and micellar casein were 0.074, 0.065 and 0.075 microg l(-1), respectively. The accuracy for the whole milk was checked by using a Certified Reference Material CRM 8435 whole milk powder from NIST, and the analytical recoveries for the milk whey and casein micelles were 100.9 and 96.9%, respectively. A mass balance study of the determination of selenium in the different milk phases was carried out, obtaining values of 95.5-100.8%. The total content of selenium was determined in 37 milk samples from 15 different manufacturers, 19 whole milk samples and 18 skimmed milk samples. The selenium levels found were within the 8.5-21 microg l(-1) range. The selenium distributions in the different milk phases were studied in 14 whole milk samples, and the highest selenium levels were found in milk whey (47.2-73.6%), while the lowest level was found for the fat phase (4.8-16.2%). A strong correlation was found between the selenium levels in whole milk and the selenium levels in the milk components.

Animals↗

Selenium-dependent and non-selenium-dependent glutathione peroxidases in human tissue extracts.

A method for the assessment of both selenium-dependent and non-selenium-dependent glutathione peroxidases on crude tissue extracts in human is described. The enzyme activity is measured by the coupled assay system in which oxidation of reduced glutathione (GSH) is coupled to NADPH oxidation catalyzed by glutathione reductase. Total glutathione peroxidase activity is measured with cumene hydroperoxide as substrate. Selenium-dependent glutathione peroxidase is measured with tert-butyl hydroperoxide. This substrate is preferable to H2O2 which gives too high blank values compared to the assay values. The difference between total glutathione peroxidase and selenium-dependent glutathione peroxidase activities represents the non-selenium-dependent glutathione peroxidase activity. Studies of substrate specificity of the two glutathione peroxidases separated by gel filtration as well as linearity and recovery studies are presented. For a given tissue, the relative amounts of the two glutathione peroxidases given by our assay are identical to those estimated by quantifying the elution peaks after gel filtration. Based on the percentages of the two glutathione peroxidases, human tissues can be classified in four groups: (1) the non-selenium-dependent glutathione peroxidase is predominant in liver, in renal cortex and skeletal muscle; (2) non-selenium-dependent and selenium-dependent glutathione peroxidases are in equal amounts in renal medulla; (3) the selenium-dependent glutathione peroxidase is predominant in adrenal glands and platelets; (4) the selenium-dependent glutathione peroxidase represents 100% of the glutathione peroxidase activity in the other organs. The heart and the brain are of special interest in this group because of the physiological role and the regulation of the selenoenzyme.

Chromatography, Gel↗