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Exogenous selenium in the brain. A histochemical technique for light and electron microscopical localization of catalytic selenium bonds.

Transcardial perfusion or intraperitoneal injections with sodium selenite result in the creation of selenium bonds that can be visualized by physical development. The present paper describes how these catalytic bonds are made visible in the tissues by surrounding them with shells of metallic silver. Based on experiments with chelating agents, the possibility that selenium-metal bonds are the catalysts is discussed. In the brain, the selenium pattern is delicate and highly laminated, the grains of silver being orderly arranged corresponding with the neuropil morphology. The precipitate is most densely packed in cortical regions. The difference in staining intensity seen in different regions of the CNS reflects the density of selenium reactive terminals. The visualized selenium bonds are predominantly located within boutons, and examination in the electron microscope reveals accumulation in the presynaptic regions. In a few places precipitates can also be found in axons, but have not been observed in perikarya or dendrites. The only non-neuronal locations of selenium were sparsely scattered, astrocyte-like neuroglia, predominantly found in the cerebellum and the hypothalamus; infrequently a few blood vessels were also stained. Sections from kidney and liver are presented as examples of localizations outside the CNS of exogenous selenium.

Animals↗

Formation of a selenium-substituted rhodanese by reaction with selenite and glutathione: possible role of a protein perselenide in a selenium delivery system.

Selenophosphate is the active selenium-donor compound required by bacteria and mammals for the specific synthesis of Secys-tRNA, the precursor of selenocysteine in selenoenzymes. Although free selenide can be used in vitro for the synthesis of selenophosphate, the actual physiological selenium substrate has not been identified. Rhodanese (EC ) normally occurs as a persulfide of a critical cysteine residue and is believed to function as a sulfur-delivery protein. Also, it has been demonstrated that a selenium-substituted rhodanese (E-Se form) can exist in vitro. In this study, we have prepared and characterized an E-Se rhodanese. Persulfide-free bovine-liver rhodanese (E form) did not react with SeO(3)(2-) directly, but in the presence of reduced glutathione (GSH) and SeO(3)(2-) E-Se rhodanese was generated. These results indicate that the intermediates produced from the reaction of GSH with SeO(3)(2-) are required for the formation of a selenium-substituted rhodanese. E-Se rhodanese was stable in the presence of excess GSH at neutral pH at 37 degrees C. E-Se rhodanese could effectively replace the high concentrations of selenide normally used in the selenophosphate synthetase in vitro assay in which the selenium-dependent hydrolysis of ATP is measured. These results show that a selenium-bound rhodanese could be used as the selenium donor in the in vitro selenophosphate synthetase assay.

Animals↗

Comparative effect of selenate and selenite on serum selenium concentration and glutathione peroxidase activity in selenium-depleted rats.

The biological effect of selenate and selenite was compared in selenium-depleted rats by using both serum selenium concentration and glutathione peroxidase activity as an indicator of body selenium status. A single oral dose of selenium (125 micrograms/kg body weight) as sodium selenate or sodium selenite increased serum selenium concentration and glutathione peroxidase activity significantly (p less than 0.001). The effect of selenate and selenite on serum selenium and glutathione peroxidase activity was similar. Serum selenium concentration correlated positively with serum glutathione peroxidase activity both before (r = 0.815; p less than 0.001) and after (r = 0.800; p less than 0.001) treatment. These results indicate that the biological availability of selenate and selenite is similar.

Administration, Oral↗

[Effect of vitamin B6 status on selenium retention in the tissues in rats fed selenium from sodium selenate].

OBJECTIVE: To study the effect of vitamin B6 status on selenium retention in tissues. METHODS: Weaning male Wistar, 4-week-old, fed with vitamin B6-selenium-deficient basal diet for 3 weeks was randomly divided into 6 groups. There were six experimental diets, that is basal diet (vitamin B6-selenium-deficient), basal diet supplemented with vitamin B6, and supplemented with Se 0.25 mg/kg as Na2 SeO4 and vitamin B6 0, 1.0 2.5 and 5.0 mg/kg diet as pyridoxine HCl for 4 weeks, three-days metabolic test was carried out before finished the study. RESULTS: Compared with each group supplemented with vitamin B6, the vitamin B6 deficient groups had a significantly low body weight gain and diet availability, and lower selenium retention in heart, liver, and kidneys, however, the status of vitamin B6 had no significant effect on the weight and selenium retention in the testes. Vitamin B6 had no significant influence on the selenium apparent absorption and retention by the three days metabolic test. CONCLUSION: Providing adequate vitamin B6 could be benefit for improving rat growth and development and increasing selenium retention in the tissues.

Animals↗

The effect of nationwide selenium enrichment of fertilizers on selenium status of healthy Finnish medical students living in south western Finland.

In Finland commercial fertilizers have been enriched with sodium selenate since July 1, 1984 in order to compensate for the poor selenium content of the soil. Fertilizers that are used for the production of hay and fodder were supplemented with 6 mg/kg of selenium, whereas fertilizers used for the production of cereals were supplemented with a higher dose, 16 mg/kg fertilizer. The effects of selenium fertilization were first seen in diary products in June 1985, and from the beginning of August 1985, the effect was evident also in wheat flour, beef, and bovine liver. In this study the selenium status of 108 healthy young adults has been systematically documented since November 1985, at which time the mean selenium serum level (S-Se) was 1.05 umol/L. A steady increase was observed until November 1989, when the maximum level, with a mean of S-Se 1.6 umol/L was reached. After that, a slight decrease has occurred. The mean serum selenium level in autumn 1991 in a new group of 35 students was 1.58 umol/L. This decrease can be explained by the high amount of imported cereals in 1988 and 1989, which was reflected also in the serum selenium levels. The glutathione peroxidase activity in erythrocytes in 1989-1990 was at the same level as in 1985 and 1986.

Adolescent↗

Effects of concurrent administration of monensin and selenium on erythrocyte glutathione peroxidase activity and liver selenium concentration in broiler chickens.

Different toxic doses of selenium and monensin preparations were administered to broiler chickens. The two substances were given by oral route, alone or concurrently, for variable periods. Erythrocyte glutathione peroxidase (GSH-Px) activity was found to be elevated after the administration of the drugs. This increase was considerably higher when selenium and monensin were administered concurrently, indicating the occurrence of strong interaction between them. Administration of selenium led to a rapid increase in the liver selenium concentration. This increase, in turn, was enhanced by concurrent application of monensin. Monensin given alone did not have any significant effect on the changes of liver selenium concentration. Further results suggest that administration of monensin increases erythrocyte GSH-Px activity, even in the absence of supplemental selenium or during increased liver selenium concentration.

Administration, Oral↗

Temporal changes in tissue glutathione in response to chemical form, dose, and duration of selenium treatment. Relevance to cancer chemoprevention by selenium.

Selenium has been reported to affect glutathione (GSH) concentrations in short-term animal-feeding experiments. Given the central role that this tripeptide plays in maintaining cellular homeostasis, it was hypothesized that perturbations in glutathione metabolism induced by selenium might account for its cancer chemopreventive activity. In the present study, four experiments were conducted in which the effect of acute, short-, or long-term exposure to selenium was assessed. Selenium was provided as either sodium selenite or D,L-selenomethionine. Selenite was observed to induce a biphasic response in total liver GSH. Injected selenium caused an acute reduction in GSH, whereas short-term feeding (up to 8 wk) increased both total GSH and oxidized glutathione (GSSH), an effect that gradually diminished in magnitude with prolonged feeding. Our data suggest that such changes are unlikely to account for the chemopreventive activity of selenium for the following reasons: Perturbations in glutathione metabolism occurred only at doses of selenite that approached toxicity. These doses are higher than what would be required for producing cancer chemoprevention. The transient nature of these changes also contrasts with the need for a continuous supplementation of selenite in suppression of tumorigenesis. Furthermore, selenomethionine was found to have little activity in altering glutathione metabolism, even though it compares favorably with selenite as a cancer chemopreventive agent. Nonetheless, these findings do not discount the possibility that sulfhydryl compounds, such as glutathione, might be used to modify the toxicity and/or enhance the cancer prophylactic activity of selenium compounds.

Animals↗

Mobilization of selenium by a selenium-dependent bacterium.

A selenium-dependent bacterium, Bacillus sp., failed to grow on selenium-free media. However, it is able to grow at high concentrations of sodium selenite containing media up to 3% (w/v). It accumulated extraordinary high quantities of selenium, 432 ppm/mL. The bacterium generated the transformation of inorganic selenium into volatile selenium form(s) into the atmosphere. The biological release of volatile selenium basically depended on several factors: incubation temperature, pH, incubation periods, and substrate concentration. Maximal quantity of the volatile selenium form was obtained at 30 degrees C, pH 7, and 1% (w/v) sodium selenite.

Bacillus↗

Study of the bioavailability of selenium in cows' milk after a supplementation of cow feed with different forms of selenium.

The purpose of the work described in this paper was to develop an easy and quick in-vitro method for comparing the bioavailability of selenium in cows' milk after different cow feed. The study focuses on bioavailability differences resulting from the use of different selenium species (organic selenium as selenised yeast and sodium selenite) for supplementation of forage. A procedure for determination of selenium in cows' milk and dialysates, by hydride-generation atomic-fluorescence spectrometry (HG-AFS) after microwave-assisted acid digestion, was optimised. The results show it is possible to obtain cows' milk enriched with selenium at different concentration without altering the original composition of the milk. The bioavailability was statistically greater for cows' milk obtained after supplementation of forage with organic selenium at levels of 0.4 and 0.5 microg Se g(-1) than for that obtained after supplementation with inorganic and organic selenium at levels of 0.2 and 0.3 microg Se g(-1).

Animal Feed↗

Effect of reduced glutathione treatment on selenosis, blood selenium concentration and glutathione peroxidase activity after repeated short-term selenium exposure in buffalo calves.

Effects of repeated feeding of selenium, when given alone or along with reduced glutathione, on whole blood selenium levels, selenosis and glutathione peroxidase activity, was studied in buffalo calves. After feeding 2.5 mg/kg of BW sodium selenite, good correlation was found between the onset of selenosis and whole blood selenium concentrations. Adverse effects appeared when the whole blood selenium concentrations increased above 2 microg/ml and mortality occurred when they exceeded 3.4 microg/ml. Reduced glutathione, given i.v. at 5 mg/kg of BW arrested the progress of selenosis and prevented mortality which was 100% in the sodium selenite supplemented group; also a reduced whole blood selenium concentration was noted. Whole blood selenium concentrations were a better and more sensitive indicator of selenium status than glutathione peroxidase activity alone.

Animals↗

Replenishment of selenium deficient rats with selenium results in redistribution of the selenocysteine tRNA population in a tissue specific manner.

We reported previously that the selenium status of rats influences both the steady-state levels and distributions of two selenocysteine tRNA isoacceptors and that these isoacceptors differ by a single methyl group attached to the ribosyl moiety at position 34. In this study, we demonstrate that repletion of selenium-deficient rats results in a gradual, tissue-dependent shift in the distribution of these isoacceptors. Rats fed a selenium-deficient diet possess a greater abundance of the species unmethylated on the ribosyl moiety at position 34 compared to the form methylated at this position. A redistribution of the Sec-tRNA isoacceptors occurred in tissues of selenium-supplemented rats whereby the unmethylated form gradually shifted toward the methylated form. This was true in each of four tissues examined, muscle, kidney, liver and heart, although the rate of redistribution was tissue-specific. Muscle manifested a predominance of two minor serine isoacceptors under conditions of extreme selenium-deficiency which also appeared to respond to selenium. Ribosomal binding studies revealed that one of the two additional isoacceptors decodes the serine codeword, AGU, and the second decodes the serine codeword, UCU. Interestingly, muscle and heart were the slower tissues to return to a 'selenium adequate' tRNA distribution pattern.

Animals↗

Tumorigenesis, metabolism, speciation, bioavailability, and tissue deposition of selenium in selenium-enriched ramps (Allium tricoccum).

Ramps (Allium tricoccum) were grown either in a mixture of vermiculite and peat moss or hydroponically with various concentrations of selenium as sodium selenate. The concentrations used were from 30 to 300 mg of selenium/kg of vermiculite-peat moss or from 10 to 120 mg/L in the hydroponic solutions. Levels as high as 784 mg of selenium/kg were obtained in the ramp bulbs when grown with high levels of selenium in the vermiculite-peat moss, and up to 600 mg of selenium/kg was obtained hydroponically. The predominant form of selenium in the ramp bulbs at all concentrations of selenium was Se-methylselenocysteine, with lower amounts of selenate, Se-cystathionine, and glutamyl-Se-methylselenocysteine. There was a approximately 43% reduction in chemically induced mammary tumors when rats were fed a diet with Se-enriched ramps. Dietary Se-enriched ramps for rats did not result in excessive tissue selenium accumulation or undesirable side effects. Bioavailability studies with rats indicated that selenium in ramps was 15-28% more available for regeneration of glutathione peroxidase activity than inorganic selenium as selenite. Therefore, Se-enriched ramps appear to have potential for the reduction of cancer in humans.

Allium↗

Determination of selenium in human milk by hydride cold-trapping atomic absorption spectrometry and calculation of daily selenium intake.

A technique of hydride cold-trapping atomic absorption spectrometry following microwave digestion was developed and optimized for the determination of selenium in human milk. The method was validated by the analysis of two standard reference materials (CRM milk powder). The detection limit was 0.5 ng mL(-)(1). The method was then used to analyze 78 milk samples from 38 Austrian mothers throughout their first 10 months of lactation. The mean concentration of selenium in the mother's milk decreased with the days postpartum from 23.9 +/- 12.0 microg L(-)(1) in colostrum to a plateau of 11.4 +/- 3.0 microg L(-)(1) in mature milk. On the basis of the milk selenium concentrations, the selenium intakes of the fully breast-fed infants and the lactating mothers were calculated. The selenium intake of the infants during their first 3 months of life was >8.2 microg day(-)(1). The selenium intake of the lactating mothers was 48 microg day(-)(1). Compared to the recommended dietary allowance, the fully breast-fed infants received sufficient selenium but the lactating mothers obtained less than the recommended.

Austria↗

Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.

OBJECTIVE: To present the results (to January 1996, the end of blinded treatment) of the Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 micro g daily) designed to test the hypothesis that selenium supplementation (SS) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA. MATERIALS AND METHODS: Original secondary analyses of the NPC to 1993 showed striking inverse associations between SS and prostate cancer incidence. A subsequent report revealed that this effect was accentuated among men with the lowest baseline plasma selenium concentrations. The effects of treatment overall and within subgroups of baseline prostate-specific antigen (PSA) and plasma selenium concentrations were examined using incidence rate ratios and Cox proportional hazards models. RESULTS: SS continued to significantly reduce the overall incidence (relative risk and 95% confidence interval) of prostate cancer (0.51, 0.29-0.87). The protective effect of SS appeared to be confined to those with a baseline PSA level of <or= 4 ng/mL (0.35, 0.13-0.87), although the interaction of baseline PSA and treatment was not statistically significant. Participants with baseline plasma selenium concentrations only in the lowest two tertiles (< 123.2 ng/mL) had significant reductions in prostate cancer incidence. A significant interaction between baseline plasma selenium and treatment was detected. CONCLUSION: To the end of the blinded treatment the NPC trial continued to show a significant protective effect of SS on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline PSA and plasma selenium concentrations.

Biopsy↗

Selenium-dependent metabolism of purines: A selenium-dependent purine hydroxylase and xanthine dehydrogenase were purified from Clostridium purinolyticum and characterized.

During purification of the selenium-dependent xanthine dehydrogenase (XDH) from Clostridium purinolyticum, another hydroxylase was uncovered that also contained selenium and exhibited similar spectral properties. This enzyme was purified to homogeneity. It uses purine, 2OH-purine, and hypoxanthine as substrates, and based on its substrate specificity, this selenoenzyme is termed purine hydroxylase (PH). The product of hydroxylation of purine by PH is xanthine. A concomitant release of selenium from the enzyme and loss of catalytic activity on treatment with cyanide indicates that selenium is essential for PH activity. Selenium-dependent XDH, also purified from C. purinolyticum, was found to be insensitive to oxygen during purification and to use both potassium ferricyanide and 2,6-dichloroindophenol as electron acceptors. Selenium is required for the xanthine-dependent reduction of 2, 6-dichloroindophenol by XDH. Kinetic analyses of both enzymes revealed that xanthine is the preferred substrate for XDH and purine and hypoxanthine are preferred by PH. This characterization of these selenium-requiring hydroxylases involved in the interconversion of purines describes an extension of the pathway for purine fermentation in the purinolytic clostridia.

Alcohol Oxidoreductases↗

Changes in the chemical form of selenium observed during the manufacture of a selenium-enriched sourdough bread for use in a human nutrition study.

High-performance liquid chromatography interfaced with inductively coupled plasma mass spectrometry, and hydride generation-inductively coupled plasma mass spectrometry were used, respectively, to investigate changes in both the chemical form and the concentration of selenium during its bio-incorporation and bio-accumulation into rye seedlings. A 60-fold increase in the total level of selenium in the seedlings ('control' biomass = 0.99 mg kg(-1), 'enriched' biomass = 55.27 mg kg(-1)) was accompanied by a change from selenite to several organo-selenium forms, with more than 40% being present as selenomethionine. The seedling biomass was dried, ground and used as an ingredient in the production of a fermented sourdough bread (popular in Poland and many Eastern European countries). The selenium in the resulting bread was also characterized in terms of its speciation, as well as its total selenium content ('control' bread = 0.06 mg kg(-1), 'enriched' bread = 3.56 mg kg(-1)). The breads were then fed to 24 volunteers as part of a human intervention study designed to establish the efficacy of this mode of selenium supplementation. The human study data subsequently showed the bread was a good source of dietary selenium.

Biomass↗

A 1-y trial of the effect of high-selenium bread on selenium concentrations in blood and toenails.

The concentration of selenium in toenail clippings and blood reflects dietary intake better than does intake calculated from dietary data because of the highly variable selenium concentration in different samples of the same food. However, the time course of selenium intake in relation to subsequent concentrations in toenail clippings is unclear. Therefore, 12 males were fed high-dose (4.91 mumol Se/d), medium-dose (2.61 mumol Se/d), or control (0.41 mumol Se/d) whole-wheat-bread for 1 y and the concentration of selenium was measured in toenail clippings collected every 12 wk for 2 y. Toenail selenium concentration was unaffected by dietary intake in the previous 3 mo and appeared to provide a time-integrated measure of intake over a period of 26-52 wk. Use of selenium concentration in toenail clippings may be an alternative to blood when a measure of long-term average intake is desired. The absence of a short-term effect of diet on toenail selenium concentration also makes this a useful marker of intake in retrospective studies.

Adult↗

Growth, reproduction rates and mammary gland selenium concentration and glutathione-peroxidase activity of BALB/c female mice fed two dietary levels of selenium.

This research was designed to determine the effect of various levels of dietary selenium on growth of BALB/c female mice. The selenium concentration and glutathione peroxidase (GSH-Px) activity in different developmental stages of the mammary gland was determined in the female mice fed 0.03 and 1.5 ppm Se. The development stages studied were: virgin (at 20 and 26 weeks of age), pregnant, lactating and involuted mammary gland. Also, the effect of the two levels of dietary selenium (0.03 and 1.5 ppm Se) on second generation reproductive rates were determined. There was no effect of dietary selenium (0.03, 0.20 or 2.00 ppm Se) on the growth rate of the mice except during pregnancy. The pregnant mice fed the 1.5 ppm Se diet had a greater growth rate than the mice fed the 0.03 ppm diet. Selenium levels in the mammary glands were higher in mice fed the 1.5 ppm Se diet than those fed the 0.03 p]pm Se diet. However, only in the mice with the highest growth rate, 10-week-old virgins, pregnant and lactating mice, was there an effect of dietary selenium on mammary gland GSH-Px activity. The reproductive rates for the second generation mice fed the two diets were similar to rates of mice fed stock diet. When both mating pairs (male and female) consumed the 0.03 ppm Se diet, the reproductive rates were lower than all other mating pairs. Thus, two conclusions can be made from these studies. First, as measured by growth and reproductive capabilities there were no signs of toxicity in mice fed the 1.5-2.0 ppm Se diet. Secondly, the differentiative states of the mammary gland influenced the selenium requirement for GSH-Px activity

Aging↗