Metabolism of selenite in men with widely varying selenium status.

OBJECTIVE: This study was undertaken to investigate the metabolism of selenite in men with life-long intakes of deficient, adequate and excess selenium. METHODS: Stable isotopes of selenium were infused for five hours into Chinese men living in deficient, adequate or excessive selenium areas, and 24-hour urine and blood samples were collected daily for the next seven days. Stable isotopic selenium excretion was determined in urine and in whole plasma and plasma fractions. RESULTS: Even though there was a positive correlation of selenium intake with the urinary excretion of this element, this relationship was not linear over the entire range (deficient, adequate, excessive) of selenium intake. When the urine excretion was normalized internally within each group, a sharp increase in the slope of this relationship was found when long-term intake increased to adequate amounts, but the slope reached a plateau when the daily intake exceeded the adequate group. The plasma selenoprotein P fraction was labeled initially, but the incorporation in the glutathione peroxidase fraction subsequently increased by a small amount. A two-month dietary restriction of selenium of the subjects from the excess area did not result in a reduction of urinary excretion of infused selenite. CONCLUSION: A complex relationship exists between long-term intake of selenium and selenium status, and subjects living in the excess area are more saturated with selenium than anticipated. More than two months of depletion are required to affect urinary excretion of selenium.     

Effects of cyanide on selenium metabolism in rats

Adult male rats were given drinking water containing either 0 or 150 ppm cyanide for 2 weeks. They were then injected with 5 microCi 75Se-selenite, and excretion of radioactivity in urine and feces was determined. No difference in excretion of 75Se occurred during the rapid phase, but the cyanide-treated rats (T1/2 28 days) excreted significantly more 75Se in urine than control (T1/2 38 days) rats. Cyanide had no effect on excretion of 75Se in feces or on the distribution of 75Se in cytosolic proteins in liver, kidney, muscle or testes. In a second experiment weanling male rats were given water with either 0 or 150 ppm cyanide and were killed for glutathione peroxidase assay and selenium analysis in blood, kidney, liver, muscle and testes after 3, 6 or 9 weeks of treatment. Glutathione peroxidase activity and selenium concentrations were significantly reduced by cyanide in all tissues except testes.     

Dose-response relations in urinary excretion of trimethylselenonium in the rat

75Se-labeled selenite was administered to fasting rats by orogastric intubation (1.5-3000 micrograms/kg body wt). Urine was collected and characterized for total radioactivity as well as for radiolabeled trimethylselenonium (TMSe). At lower doses of selenite (up to 500 micrograms/kg body wt), 30% of the administered dose was excreted. At higher doses of selenite, fractional urine excretion decreased as a function of the dose. The observed decrease in fractional urine excretion was not caused by changes in the absorption of the administered radiolabel. There was a direct relationship between the amount of the administered dose of selenite (up to 1500 micrograms/kg body wt) and the proportion of urinary [75Se] excreted as TMSe. Pretreatment with seleno compounds (10 or 100 micrograms Se/kg body wt as selenite, or selenomethionine) for 35 d before a challenge dose of [75Se]selenite did not influence the excretion of total [75Se] or of [75Se]TMSe in urine. Ingestion of a choline-deficient diet, which should deplete the availability of methyl groups, did not have any effect on excretion of total [75Se] or of [75Se]TMSe in urine after a challenge dose of [75Se]selenite (500 micrograms/kg body wt). The data presented here permit the following conclusions: 1) Production of TMSe is dose dependent, 2) production of TMSe from a single acute dose does not depend on the history of selenium intake and 3) rats fed a methyl-deficient diet are able to eliminate Se via formation of TMSe.     

Absorption and retention of 75SeO3 in relation to soybean protein intake in the rat

The absorption and retention of ⁷⁵Se, given as an oral dose of ⁷⁵SeO₃, was studied in young male rats receiving different levels and sources of soy protein, with and without selenite and methionine supplementation. Rats fed a protein-free diet had a higher cumulative urine ⁷⁵Se excretion and a sligtly lower ⁷⁵Se absorption and ⁷⁵Se retention than rats fed diets containing 10% protein supplied as soya flour. Results indicated that supplementation with selenite decreased the fractional absorption and retention of selenium, but the overall effect was a marked increase in the total amount of selenium ingested, absorbed and retained. Methionine supplementation of a diet based on soya increased growth and PER: it also decreased slightly cumulative feces ⁷⁵Se excretion and increased ⁷⁵Se absorption, but only in rats fed diets supplemented with selenium. The present findings are consistent with the view that selenium homeostasis in the rat is maintained largely through changes in the urinary excretion of selenium and they show that an inadequate protein diet reduces the efficiency of retention of absorbed selenite.     

Effects of dietary copper, cadmium, iron, molybdenum and manganese on selenium utilization by the rat

The possible antagonistic effects of different dietary concentrations of copper (1.3-200 mg/kg), cadmium (1-5 mg/kg), iron (20-500 mg/kg), molybdenum (0.3-50 mg/kg) and manganese (0.2-200 mg/kg) on selenium utilization by the rat were studied by the measurement of the absorption and organ distribution of dietary selenium as [75Se]selenite and by effects on organ glutathione peroxidase (GSH-Px: EC 1.11.1.9) activity. Although a high concentration of copper (200 mg/kg) in the diet did not alter the percentage absorption and total-body retention of doses of 75SeO3(2)- by rats, after such treatment tissue 75Se distribution was changed and was lower total selenium in some tissues. After copper treatment (200 mg/kg diet) GSH-Px activity of liver, testis, kidney and whole blood was also lower. Dietary cadmium, iron, molybdenum and manganese at the concentrations investigated had no significant effects on selenium metabolism. Thus it is unlikely that copper, cadmium, iron, molybdenum and manganese at normal dietary concentrations will have a major effect on selenium metabolism in the rat, especially if adequate amounts of selenium are being consumed.     

Absorption, distribution and excretion of selenium from beef and rice in healthy North American men

Previous metabolic studies of selenium used pure selenium compounds with pharmacologic activities unrelated to selenium nutrition. Healthy men were fed foods naturally high or low in selenium while confined to a metabolic research unit. Selenium intake was 47 microg/d (595 nmol/d) for 21 d while energy intakes and body weights were stabilized and selenium excretion and intake came into metabolic balance. On d 22, selenium intake was changed to either 14 microg/d (177 nmol/d, low selenium) or 297 microg/d (3.8 micromol, high selenium) for the remaining 99 d. The absorption, distribution and excretion of selenium in food were similar to selenomethionine, and distinctly different from sodium selenite. Daily urinary selenium excretion and selenium concentrations in plasma and RBC showed the largest responses to selenium intake relative to interindividual variation. Urinary selenium and plasma selenium responded most rapidly to changes in selenium intake, whereas RBC reflected longer-term selenium intake. Given the difficulty of 24-h urine collections outside a metabolic research unit, RBC and plasma selenium seem to be the most useful indicators of selenium intake. During the intervention period, the high selenium group retained 15 mg (190 micromol) of selenium, with approximately 5 mg (63 micromol) going into skeletal muscle. The low selenium group lost only 0.9 mg (11 micromol) of whole-body selenium but lost 3.3 mg (42 micromol) from muscle, indicating that selenium was redistributed from muscle to tissues that have a higher metabolic priority for selenium such as testes. Fecal excretion decreased by half, representing an important but previously underappreciated adaptation to selenium restriction.     

Dynamics of selenite metabolism in young men: studies with the stable isotope tracer method

Dynamics of selenite metabolism in young adult North American men were studied using an amino acid diet and the stable isotope tracer methodology during a short-term selenium replete-restriction phase. During the initial 10 days subjects consumed the diet providing a total daily selenium intake of 107.7 +/- 0.1 micrograms mostly as selenite. This was followed by selenium restriction at 11.4 +/- 0.1 micrograms/day (as impurities from diet components) for the next 34 days. Kinetic studies with the stable isotope tracer 74SeO32- were carried out on days 4 and 39 of the study. Kinetics of excretion of the tracer in feces and urine were followed from which body retention curves were constructed. The retention curves were resolved into two exponential decay components with half-lives of 2.4 +/- 0.3 and 162 +/- 9 days (mean +/- 1 SEM), respectively. Retention data and urine isotope enrichment curves were combined to determine dynamics of changes in the apparent body pool size for selenite (10.4 mg at t----infinity) as well as rates of turnover for this parameter.     

Kinetics of a single administration of 74Se-selenite by oral and intravenous routes in adult humans

The purpose of this study was to explore the fate of a single dose of labeled selenium as determined by its route of administration. Thus, the appearance of a stable isotope of selenium, administered as 74-Se-selenite, was measured in plasma, urine, and feces, with neutron activation analysis, following a 81.7 micrograms dose of 74Se-selenite given either intravenously or orally in two groups (n = 4) of healthy, young adult men, who were otherwise maintained on a diet providing a constant and adequate selenium intake. From these isotopic data, measurable parameters of urine excretion, total body retention and selenite-exchangeable metabolic pool (Se-EMP) were defined to provide a quantitative assessment of selenium metabolism in these subjects. The initial 24-hr urine excretion of the label was higher for the intravenously administered label (18.2 +/- 2.1% of dose) compared to the oral dose (11.7 +/- 2.6% absorbed dose). Thereafter, the excretion of isotope was the same for both groups. For equivalent entry of Se into the body, measured total body retention and Se-EMP were the same for both groups. These initial kinetic data suggest that the overall utilization of selenium from a single administration of selenite is comparable for the two routes of intake and that the host's selenium requirement can probably be met adequately via the intravenous administration of selenite.     

The uptake, metabolism, and biological half-life of benzo[a]pyrene administered by force-feeding in sea bass (Dicentrarchus labrax).

The kinetics of uptake and metabolism of benzo[a]pyrene (BaP) were studied in various tissues of a marine fish, the sea bass (Dicentrarchus labrax), after intragastric administration of pellets containing a 14C-labeled compound. Only 25% of injected radioactivity was detected and it was found only in intestine, gallbladder, liver, and kidney. The major part of radioactivity was found in gallbladder (85% of the whole body radioactivity). The calculated half-lives determined after the decrease in radioactivity measured in these tissues were 8.2, 3.5, 3.3, and 0.8 days for liver, gallbladder, intestine, and kidney, respectively. The kinetics of distribution of radioactivity between alkali and hexane tissue extracts showed the high metabolization potential of intestine which represents the main site of BaP uptake by this route of exposure. The other organs received mainly metabolites brought by general blood circulation. Intragastric administration as an experimental exposure route compared to other exposure patterns and particularly intraperitoneal injection, which has been used previously in the same species and under the same experimental conditions for the same kind of study, is discussed.     

Comparative acute toxicity and bioconcentration of selenium by the midge Chironomus decorus exposed to selenate,selenite, and seleno-DL-methionine

The increased flux of selenium into aquatic ecosystems due to anthropogenic activities has resulted in the degradation of several systems. Initial experiments examined the comparative acute toxicity of waterborne selenate, selenite, and seleno-DL-methionine to fourth instar Chironomus decorus larvae resulting in 48-h LC₅₀ concentrations of 23.7, 48.2, and 194 mg Se/L, respectively. The relative toxicities of the selenium forms are reversed compared to previous studies on other species and demonstrate that relative waterborne selenium toxicity is species specific. Studies examining the kinetics of selenate and selenite (the dominant waterborne forms) accumulation by C. decorus larvae exposed to the 48-h LC₅₀ selenium concentrations showed initial rapid uptake and subsequent plateauing with maximum concentrations attained by 16 h. The final whole body selenium levels were approximately 63 mg Se/kg for selenate and 85 mg Se/kg for selenite. Comparative bioconcentration experiments demonstrated that after 48 h selenium accumulation was greater in larval C. decorus exposed to 25 mg Se/L as seleno-DL-methionine than in those exposed to 25 mg Se/L as selenate and selenite.     

All regions of mouse brain are dependent on selenoprotein P for maintenance of selenium

The brain and testis retain selenium better than other tissues during selenium deficiency. Studies of mice with selenoprotein P (Sepp1) deleted (Sepp1(-/-) mice) showed that brain and testis selenium levels are largely dependent on Sepp1. Therefore, we examined tissue selenium in mice fed varying amounts of selenium and in Sepp1(-/-) mice to characterize better the role(s) of Sepp1. Mice were fed a selenium-deficient diet for 8 wk supplemented with selenium as selenite from none to 0.25 mg/kg diet and tissue selenium was measured. Brain and testis maintained their selenium better than did liver, kidney, and muscle when dietary selenium was limiting but testis selenium fell sharply in the group fed the deficient diet. Brain retained its selenium well, even in the group fed the deficient diet. After intravenous injection of (75)Se-Sepp1 into Sepp1(-/-) and Sepp1(+/+) mice, qualitative differences between brain and testis (75)Se uptake were noted, further suggesting differences in their uptake of selenium from Sepp1. Finally, selenium was measured in brain regions of Sepp1(-/-) and Sepp1(+/+) mice fed the diet supplemented with 1 mg selenium/kg and Sepp1(+/+) mice fed the deficient diet. Deletion of Sepp1 and selenium deficiency each lowered selenium a similar amount in cortex, midbrain, brainstem, and cerebellum. Selenium in the hippocampus was lowered by deletion of Sepp1 but not by selenium deficiency. These results suggest that Sepp1 is more important for maintaining selenium in the hippocampus than in other brain regions. They also confirm the position of the brain at the apex of the organ selenium hierarchy.     

Uptake of selenium-75 by human lymphocytes in vitro.

Selenite uptake by human lymphocytes was studied both in whole blood and in isolated cells. When 75Se-selenite (75Se-SeO3-2--) is supplied to whole blood, it is converted by the erythrocytes to a form which rapidly becomes bound to plasma proteins. Studies with a variety of inhibitors indicated that the process is not energy dependent but that sulfhydryl groups are required. The 75Se bound to plasma proteins is absorbed by lymphocytes in preference to 75SeO3-2-. By the use of selective inhibitors (respiratory, sulfhydryl, protein biosynthetic) it was demonstrated that the uptake of either form of 75Se requires neither energy nor protein synthesis; however, all the sulfhydryl inhibitors cause a decrease of absorption. A scheme which summarizes the pathway of selenite conversion in human blood and uptake by lymphocytes is presented; the data indicate that plasma proteins function as carriers of selenium to lymphocytes.     

Chemical forms of selenium in rat tissues after administration of selenite or selenomethionine

The chemical forms of selenium (Se) were determined in erythrocyte and liver proteins after injection of 75Se as either sodium selenite or selenomethionine (Se-Met) in male weanling rats. Gel-filtration chromatography (Sephadex G-150) of erythrocyte lysate revealed labeling of four fractions corresponding to void volume proteins, glutathione peroxidase (GPx), hemoglobin (Hb) and low-molecular-weight materials. Acid hydrolysates of erythrocyte protein fractions and whole liver were analyzed by ion-exchange chromatography (Dionex DC6A). Void volume proteins contained principally selenocysteine (75Se-Cys) in [75Se]selenite-injected animals. This material contained both 75Se-Met and 75Se-Cys 1 d postinjection in 75Se-Met-injected animals, but primarily 75Se-Cys at 20 d afterwards. GPx contained 75Se as 75Se-Cys regardless of the selenium compound injected. Hb of 75Se-Met-injected animals contained principally 75Se-Met at both 1 and 20 d postinjection. In [75Se]selenite-injected animals, 75Se was present in hemoglobin as two unidentified forms. In acid hydrolysates of whole liver 75Se was recovered principally as 75Se-Cys from animals injected with [75Se]selenite. For animals injected with 75Se-Met, liver 75Se was present initially as 75Se-Met, but after 5 d the majority of liver 75Se was as Se-Cys. No differences were found in deposition of 75Se in liver, kidney, testes, erythrocytes or plasma in rats injected with labeled selenite or Se-Met, but a significantly greater retention was found in muscle of Se-Met-injected rats as compared to those given selenite.     

锰对大鼠硒代谢的影响

鉴于贫硒与克山病发病有密切关系以及一些病区的人群既贫硒又富锰,本文研究了锰对大鼠硒代谢的影响。经腹腔给大鼠注射40mg/kg氯化锰5周,致血清和心肌锰含量明显增高,而血清和心肌硒含量以及全血和心肌谷胱甘肽过氧化物酶活性却显著降低。组织锰含量与硒含量和谷胱甘肽过氧化物酶活性呈负相关。在给予氯化锰的第7天,经胃管给予~(75)硒,锰组大鼠在服~(75)硒之后7天中总排硒量显著高于对照组大鼠,主要是由于锰促进慢相尿硒排泄所致。结果表明,锰对硒代谢有明显影响,即通过增加硒排泄量而致血、心肌硒含量和含硒酶活性显著降低。     

Uptake of 75Se-selenite by brush border membrane vesicles from chick duodenum stimulated by vitamin D

Brush border membrane vesicles were isolated from mucosal homogenates of duodena from normal, rachitic and vitamin D-treated rachitic chicks using a discontinuous sucrose gradient, and further purified by glycerol gradient centrifugation. In vitro uptake of 75Se-selenite by purified brush border membrane vesicles was studied using a rapid filtration technique. The time course of 75Se uptake was non-linear; rapid initial binding was followed by a gradual decrease in the rate of uptake until an equilibrium value was reached at 60-120 min. The initial binding at 36 s was not affected by selenite concentration in the incubation buffer, while the fractional rate of uptake between the 36 s and 2 min time periods was clearly lower with 1 mM Se than with 4-100 microM Se. 75Se uptake did not show any dependency on the external Na-gradient, nor could it be inhibited by other anions (arsenate, phosphate). Treatment of rachitic chicks either with cholecalciferol (500 Iu, 72 h) or with 1,25(OH)2-cholecalciferol (0.5 microgram given 16 h prior to isolation of the vesicles) significantly enhanced 75Se uptake. A threefold excess of mannitol in the outside buffer reduced 75Se uptake by vesicles from vitamin D-deficient and D-treated chicks 60% and 35% respectively, but had no effect on vesicles from vitamin D-treated chicks preloaded with 75Se. Neither saponin treatment nor excess cold selenite could release the label from the vesicles preloaded with 75Se. These data are compatible with the hypothesis that selenite easily crosses the brush border membrane into the intravesicular space and, once inside, is tightly bound by the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring vitamin E pools in sheep tissue and plasma after intravenous dosing of radiotocopherol

The fate of radiotocopherol was studied in plasma and tissues of sheep at various intervals after injection of single intravenous doses of 3H-labelled D-alpha-tocopherol. Plasma samples were taken at regular intervals after dosing and selected tissues were taken from all sheep after slaughter and assayed for radioactivity and D-alpha-tocopherol. Sheep were killed in groups of five at 24, 72, 96, 272 and 432 h post-dosing. Plasma profiles were characterized as a sum of three exponential terms. A principal component analysis of tissue concentrations was carried out to identify tissues with parallel profiles of log (disintegrations/min per microgram) over time. Five groups of tissues with distinct uptake and elimination processes were identified. The D-alpha-tocopherol in the liver and heart appeared to be consistent with the post-distributive kinetics of a highly perfused shallow compartment, while lung kinetics appeared to reflect a non-linear kinetic process. The third group, which included the spleen, neck brachiocephalicus muscle and pancreas, had depletion rates parallel to those of plasma for 24-272 h, but slower decreases than plasma over 272-432 h. Hip gluteus muscle and kidney comprised a fourth group, with depletion parallel to plasma rates for 24-96 h but progressively slower than plasma decreases over 96-272 h. Adrenal kinetics resembled the fourth group, but had a more rapid decrease in specific activities over 24-72 h.     

Selenium from selenium-rich Spirulina is less bioavailable than selenium from sodium selenite and selenomethionine in selenium-deficient rats

The bioavailabilty of selenium (Se) from selenium-rich Spirulina (SeSp) was assessed in Se-deficient rats by measuring tissue Se accumulation and glutathione peroxidase (GSH-Px) activity. For 42 d, rats were subjected to dietary Se depletion by consumption of a Torula yeast (TY)-based diet with no Se; controls were fed the same diet supplemented with 75 microg Se/kg diet as sodium selenite. Se-deficient rats were then repleted with Se (75 microg/kg) by the addition of sodium selenite, selenomethionine (SeMet) or SeSp to the TY basal diet. Selenium speciation in SeSp emphasized the quasi-absence of selenite (2% of total Se); organic Se comprised SeMet (approximately 18%), with the majority present in the form of two selenoproteins (20-30 kDa and 80 kDa). Gross absorption of Se from SeSp was significantly lower than from free SeMet and sodium selenite. SeMet was less effective than sodium selenite in restoring Se concentration in the liver but not in kidney. SeSp was always much less effective. Similarly, Se from SeSp was less effective than the other forms of Se in restoring GSH-Px activity, except in plasma and red blood cells where no differences were noted among the three sources. This was confirmed by measuring the bioavailability of Se by slope-ratio analysis using selenite as the reference form of Se. Although Se from SeSp did not replenish Se concentration and GSH-Px activity in most tissues to the same degree as the other forms of Se, we conclude that it is biologically useful and differently metabolized due to its chemical form.     

Rapid uptake and clearance of pyridoxine by red blood cells in vivo

There is rapid pyridoxine (PN) uptake in vitro into red cells where it is converted to pyridoxal (PL) forms. To assess uptake in vivo, the equivalent of 48.6 and 118 mumol PN were given intravenously to a healthy female subject. Vitamin B-6 compounds were measured by a Lactobacillus casei microbiological assay in blood taken 1-60 min after injection. After either injection there was a considerable amount of PN in the red cells at 1 min but by 3 min a large amount of that PN had disappeared, mostly unaccounted for by conversion to PL forms. Although there was considerably less PN at 1 min in both red cells and plasma after the smaller injection, in the next 2 min similar amounts had left the red cells (4.59 and 4.30 mumol) and plasma (9.37 and 10.09 mumol), respectively, after the injections. Red cells, as well as plasma, may be transporting PN to other sites of metabolism in tissues.     

Metabolism in rats of selenium from intrinsically and extrinsically labeled isolated soy protein

Absorption, retention and tissue accumulation by rats of 75Se from intrinsically labeled isolated soy protein were compared with utilization of 75Se from the extrinsic sources of [75Se]selenite, [75Se]selenate or [75Se]selenomethionine. Extrinsic sources of selenium were given by gavage or mixed with isolated soy protein. There were no differences in absorption and retention of 75Se from intrinsically labeled soy diet compared to the three extrinsically labeled soy diets. Of the three extrinsic sources tested, 75Se from selenate was better absorbed than from selenite or selenomethionine when incorporated into a soy diet. Absorption of 75Se was significantly lower when given to animals in gavage solution than when mixed with soy diets. After a 14-d test period, retention of 75Se was the same for all four soy diet groups. In gavaged groups, 75Se from selenomethionine was retained to a greater extent than 75Se from selenite. The liver, testes and kidney accumulated more 75Se from the test meal than did the blood and lungs. In the testes more 75Se from selenite and selenate was accumulated than from selenomethionine-labeled diets. Selenium absorption from the soy isolate source was very high (86-96%), indicating that, although soy does not normally contain high levels of selenium, the selenium present is well absorbed from this plant source.     

Vitamin B6 dependence of selenomethionine and selenite utilization for glutathione peroxidase in the rat.

The biological availability of selenium from sodium selenite and selenomethionine for glutathione peroxidase activity was studied. Rats were fed ad libitum for 2 weeks a basal diet deficient in both selenium and vitamin B6, and then for the subsequent 2 weeks the same diet supplemented with vitamin B6 (2.5 micrograms as pyridoxine-HCl/g diet) or selenium (2 microgram/g diet) or both. In the presence of vitamin B6, selenite and selenomethionine increased equally the glutathione peroxidase activity in both the liver and erythrocytes above that of selenium-unsupplemented controls. In the absence of vitamin B6, selenomethionine was less effective in the liver and ineffective in the erythrocytes while selenite was equally effective in both tissues and was as effective as in the presence of vitamin B6. These results indicate that selenite selenium is readily available for glutathione peroxidase induction as compared with selenomethionine, and establish that vitamin B6 is involved in the metabolism of selenomethionine to supply selenium for glutathione peroxidase.