A comparison of the uptake of [75Se]selenite, [75Se]selenomethionine and [35S]methionine by tissues of ewes and lambs.

The fate of selenium, given as Na2(75)SeO3, or [75Se]selenomethionine, and of [35S]methionine administered intravenously to ewes and lambs, has been examined. The main intention was to follow the incorporation of selenium into protein in a number of tissues, including liver and kidney, and to measure the extent of that incorporation of selenoamino acid, particularly with respect to the administration of selenite. The ewes chosen were lactating ewes with lambs at foot, and the lambs were animals which had been weaned on to fodder low in selenium and were recovering from white muscle disease with selenium therapy. These two experimental situations were chosen as they offered conditions under which selenium incorporation might be considered to be maximal. Entry of isotope into milk was rapid and was greater when 75Se was given as the selenoamino acid than as selenite. In both ewes and lambs greater amounts of activity, derived from selenite, were bound to plasma proteins than to the proteins of milk. This was particularly evident in samples taken some hours after administration. This ability of the plasma to bind selenium was demonstrated by alkaline dialysis. Small, though significant amounts of selenium, derived from Na2(75)SeO3, were incorporated as selenoamino acids into the proteins of liver, kidney and pancreas, as well as into the proteins of milk and plasma. In ewes, both selenomethionine and selenocystine were identified chromatographically in enzyme digests of defatted liver and kidney. Some differences occurred in the distribution of labelled compounds in organs from lactating ewes and recovering lambs. The incorporation of selenium into protein is discussed briefly in relation to the recent findings of an association between selenium and the enzyme glutathione peroxidase.     

Effect of dietary fluoride on selenite toxicity in the rat

Three factorial experiments were conducted to determine if high dietary fluoride (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and 150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on 8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were also unaffected by F. Liver Se concentration, however, was slightly (12%) but significantly (p<0.025) reduced when the highest F and Se levels were combined. Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg). Therefore, further study focused on liver histology with treatments that eliminated the middle levels of selenite and F. Fluoride prevented the hepatic necrosis seen in selenite-toxic rats. Similar histological lesions were not observed for kidney or heart. Fluoride partially (26%) but significantly (p<0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but there was no F effect on intracellular distribution of liver Se, glutathione levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the protective effect of F on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear. Oregon Agricultural Experiment Station Technical Paper No. 9728.     

Effect of sodium selenosulfate on restoring activities of selenium-dependent enzymes and selenium retention compared with sodium selenite in vitro and in vivo

Sodium selenosulfate has been extensively used as a precursor of selenide ions in the preparation of nano Se-containing compounds. Its biological properties remain completely unknown. Sodium selenosulfate and sodium selenite were added to the medium of HepG2 cells and administered intraperitoneally at a dose of 0.1 mg Se/kg body weight to selenium-deficient mice, respectively. Both of the selenium compounds could increase the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) in a dose-dependent manner in cells and efficiently restore selenium retention and activities of GPx and TrxR in mice. All of the variables were in correlation with the Se supply. There was no distinction in elevating activities of GPx and TrxR between selenosulfate and selenite in vitro. After a 2-d supply of selenosulfate, the activity of GPx in the liver was 65% (p < 0.001) and Se accumulations in the liver, kidney and blood were 64%, 86%, and 65%, respectively, of those treated with selenite (allp < 0.01). With the 7-d selenosulfate supplementation, the activity of GPx in the kidney and activities of TrxR in the liver and kidney were 88%, 75%, and 78%, respectively, of those treated with selenite (allp < 0.01); Se retentions in the liver and kidney were 85% and 93%, respectively of those supplemented with selenite (bothp < 0.01). These facts indicated that selenosulfate could be absorbed and utilized in the biological system. No difference in vitro demonstrated that selenosulfate could be absorbed and generate reduced selenide as efficiently as selenite. The differences between the two compounds in vivo were the result of other factors that affected selenosulfate utilization in tissues.     

The inhibitory effect of sodium selenite on N-nitrosodiethylamine-induced and phenobarbital promoted liver tumourigenesis in rats based on the modulation of polyamine levels

In the present study, we have evaluated the effects of dietary selenite (Se) on polyamine levels and its influence on N-nitrosodiethylamine (DEN) initiated and Phenobarbital (PB) promoted in rat liver carcinogenesis. Dietary selenite at a concentration of 4 ppm (through drinking water) was administered in rats either before initiation (4 weeks), or during promotion (16 weeks) and entire experimental period (20 weeks). Male Wistar strain of albino rats was treated with single intra peritoneal dose of DEN (200 mg kg⁻¹ body weight), after 2 weeks the carcinogenic effect was promoted by PB (0.05%; through diet). Alpha fetoprotein (AFP) was investigated after the 20th-week of experimental period. Selenite-treated animals markedly reduced the AFP during the time of pre-selenite [before initiation (4 weeks)] and entire experimental period (20 weeks), administration rather than the promotion period. This infers that anticancer property of selenite depends on the stage of carcinogenesis, rather than duration of treatment. Evaluation of polyamine levels in hepatoma and surrounding liver tissue showed significant difference in the selenite-treated groups compared with pair-fed control groups. Furthermore, histopathological examination showing remarkable difference between control and treated groups. These results demonstrate that selenite can modulate the development of DEN-induced and PB-promoted rat liver carcinogenesis through a polyamine-dependent mechanism. (Mol Cell Biochem xxx: 165–172, 2005)     

Fate of selenate and selenite metabolized by Rhodobacter sphaeroides

Cultures of a purple nonsulfur bacterium, Rhodobacter sphaeroides, amended with approximately 1 or approximately 100 ppm selenate or selenite, were grown phototrophically to stationary phase. Analyses of culture headspace, separated cells, and filtered culture supernatant were carried out using gas chromatography, X-ray absorption spectroscopy, and inductively coupled plasma spectroscopy-mass spectrometry, respectively. While selenium-amended cultures showed much higher amounts of SeO(3)(2-) bioconversion than did analogous selenate experiments (94% uptake for SeO(3)(2-) as compared to 9.6% for SeO(4)(2-)-amended cultures from 100-ppm solutions), the chemical forms of selenium in the microbial cells were not very different except at exposure to high concentrations of selenite. Volatilization accounted for only a very small portion of the accumulated selenium; most was present in organic forms and the red elemental form.     

Urinary selenium excretion in selenite-loaded sheep and subsequent Se dynamics in blood constituents

Renal selenium excretion in sheep was measured during intravenous infusion of sodium selenite, and the post-infusion dynamics of Se levels in whole blood, plasma and red blood cells (RBC) were investigated for the next 5 days. The plasma Se level increased almost twenty fold with the infusion of Na2SeO3 (from 0.39 +/- 0.02 to 7.83 +/- 0.33 micromol x L(-1), P < 0.001) compared with the baseline value. The selenium concentration in urine (0.07 +/- 0.02 vs. 18.53 +/- 2.56 micromol x L(-1), P < 0.001), the amount of Se excreted (0.14 +/- 0.07 vs. 21.40 +/- 2.31 nmol x min(-1), P < 0.001) and the renal clearance of Se (0.1 9 +/- 0.03 vs. 3.01 +/- 0.34 mL x min(-1), P < 0.001) were found to be highly significantly elevated during selenite loading. The clearance measurements showed no changes in the urinary flow rate or in the glomerular filtration rate. During and at the end of infusion the highest Se level was attained in plasma, followed by whole blood and RBC. The plasma Se level fell rapidly within 10 min after the end of infusion, but the concentration of Se in RBC was stable up to the fourth hour, when it started to decrease too. On day 5 the Se concentrations in plasma, RBC and whole blood were found to be only slightly but still significantly higher than before the selenite infusion. The large disproportion between the infusion rate of Se (8.76 microg x min(-1)) and its renal excretion rate (1.69 microg x min(-1)) found in clearance measurements suggests low glomerular filtration of infused selenium, which might primarily be caused by the binding of selenite metabolites to blood constituents. The presented results confirm the low bioavailability to ruminants of Se from sodium selenite.     

In vitro metabolism of selenite in sheep blood: factors controlling the distribution of selenium and the labelling of plasma protein.

Some factors controlling the distribution of Na275SeO3 in sheep blood were studied in vitro. After centrifuging Na275SeO3-incubated blood most of the radioactivity was found in the plasma. The labelling of plasma protein by 75Se was dependent on the presence of erythrocytes. The degree of labelling of plasma protein increased with erythrocyte concentration. When phosphate-buffered saline-washed erythrocytes were suspended in phosphate-buffered saline and incubated with Na275SeO3 the majority of the 75Se was detected in the erythrocytes. On incubating these labelled erythrocytes with unlabelled plasma there was a transfer of radioactivity to the plasma. The calculated activation energy for the labelling of plasma was 107.52 kJ/mol. Albumin was shown not to be a principal acceptor of 75Se from the erythrocytes by ammonium sulphate precipitation of radioactive plasma. Addition of Na2SeO3 to the labelled blood resulted in the transfer of 75Se from plasma to the erythrocytes. Radioactive plasma incubated at 37 degrees C was thermolabile with respect to its 75Se content whereas in whole blood the degree of 75Se binding to plasma protein did not vary suggesting that a recycling of selenium was occurring in blood. From the results presented an in vitro model of selenium metabolism in blood is postulated.     

Transformations of selenate and selenite by Stenotrophomonas maltophilia isolated from a seleniferous agricultural drainage pond sediment

A Gram-negative bacterium, identified as Stenotrophomonas maltophilia by fatty acid analysis and 16S rRNA sequencing, was isolated from a seleniferous agricultural evaporation pond sediment collected in the Tulare Lake Drainage District, California. In cultures exposed to the atmosphere, the organism reduces selenate (SeO4(2-)) and selenite (SeO3(2-)) to red amorphous elemental selenium (Se degrees ) only upon reaching stationary phase, when O2 levels are less than 0.1 mg l(-1). In 48 h, S. maltophilia removed 81.2% and 99.8% of added SeO4(2-) and SeO3(2-) (initial concentration of 0.5 mM), respectively, from solution. Anaerobic growth experiments revealed that the organism was incapable of using SeO4(2-), SeO3(2-), SO4(2-) or NO3- as a terminal electron acceptor. Transmission electron microscopy of cultures spiked with either Se oxyanion were found to contain spherical extracellular deposits. Analysis of the deposits by energy-dispersive X-ray spectroscopy revealed that they consist of Se. Furthermore, S. maltophilia was active in producing volatile alkylselenides when in the presence of SeO4(2-) and SeO3(2-). The volatile products were positively identified as dimethyl selenide (DMSe), dimethyl selenenyl sulphide (DMSeS) and dimethyl diselenide (DMDSe) by gas chromatography-mass spectrometry. Our findings suggest that this bacterium may contribute to the biogeochemical cycling of Se in seleniferous evaporation pond sediments and waters. This organism may also be potentially useful in a bioremediation scheme designed to treat seleniferous agricultural wastewater.     

Na_2SeO_3对血影收缩蛋白(spectrin)与肌动蛋白(actin)相互作用的影响

Na_2SeO_3不影响肌动蛋白(actin)的聚合,但它可通过与血影收缩蛋白(spectrin)作用而间接促进actin的聚合。Na_2SeO_3的作用具有浓度依赖性:低浓度(0.5-5.0ppm)可提高actin聚合过程的成核速度及延伸速度,高浓度则产生相反的效应。巯基试剂如N-乙基马来酰亚胺(NEM)可消除硒的效应。因此,推测适量的硒可能导致spectrin构象发生一定变化,增强spectrin与actin的结合,降低actin链解聚的倾向性,从而稳定红细胞膜骨架。     

Na_2SeO_3对血影收缩蛋白(spectrin)与肌动蛋白(actin)相互作用的影响

Na_2SeO_3不影响肌动蛋白(actin)的聚合,但它可通过与血影收缩蛋白(spectrin)作用而间接促进actin的聚合。Na_2SeO_3的作用具有浓度依赖性:低浓度(0.5-5.0ppm)可提高actin聚合过程的成核速度及延伸速度,高浓度则产生相反的效应。巯基试剂如N-乙基马来酰亚胺(NEM)可消除硒的效应。因此,推测适量的硒可能导致spectrin构象发生一定变化,增强spectrin与actin的结合,降低actin链解聚的倾向性,从而稳定红细胞膜骨架。     

Uptake and transport of selenite and selenate by soybean seedlings of two genotypes

In an attempt to address the role of biological behavior on Se uptake by soybean crop and the genotype effects, experiments with time and concentration sequences of Se uptake by seedlings in Hoagland solution are conducted using selenite and selenate respectively. Two soybean cultivars Tong-ai 405 (TA) and Qidong Green-skin (QG) are used as different genotypes. In presence of selenite, Se uptake by both roots and shoots exhibited a linear increase with the growing time at 5 M and with the solution Se concentrations. However, in presence of selenate, the linear response to growing time is only valid before 24 h of growing. While root Se uptake is much slower under selenate than under selenite in the time sequence experiment, shoot Se levels are similar between the two different Se form treatments. Nevertheless, in the experiment of concentration sequence, either root Se or shoot Se responses linearly to solution Se concentration regardless of the Se forms supplied. A big discrepancy of root Se level with a similarity of shoot Se between the two cultivars is observed in the concentration sequence experiment. This supports a much faster passive uptake of selenite but more or less an active uptake of selenate by soybean seedlings. Comparatively, cultivars TA have a consistently higher Se concentration than QG both in roots and shoots under selenate, while no difference of concentration ratio of shoot to root is recognized between them. The higher Se level in seed grains, therefore, may be accounted for not by Se transport form root to shoot but by greater ability of Se uptake and retention under selenate by the former cultivar. Therefore, not only forms of Se supply but also genotype difference affects the Se bioavailability by different soybean cultivars. This should be taken into account for screening the high Se-efficiency plants or cultivars to improve the Se supply of the food chain.     

Comparative Effect of Selenium in Wheat,Barley, Fish Meal and Sodium Selenite for Prevention of Exudative Diathesis in Chicks

Groups af White Leghorn chicks obtained from dams deprived on selenium (Se), were fed from hatching a low-Se-vitamin E basal diet alone, or supplemented with 0.02, 0.04, 0.06 or 0.08 mg Se/kg diet, as sodium selenite (Na2SeO3 · 5H2O), wheat, barley or fish meal. Prevention of the Se-vitamin E deficiency responsive disease exudative diathesis (ED) as it was clinical observed, induction of the plasma Se dependent enzyme glutathione peroxidase (GSH-Px) activity, and Se concentration in the cardiac muscle were observed to be dietary Se level and source dependent. Slope ratio assay was applied to estimate the biological availability of Se in the natural sources relative to Se in sodium selenite. For the prevention of ED, the bioavailability of Se in wheat, barley and fish meal was 99, 85 and 80 %, respectively. The increase in the plasma GSH-Px activity revealed a bioavailability for Se in wheat, barley and fish meal of 79, 71 and 66 %, respectively. Using retention of Se in the cardiac muscle as the bioassay, a bioavailability of 108, 87 and 100 % was calculated for wheat, barley and fish meal Se, respectively.     

Concentrations of essential elements after repeated administrations of tin and selenium

To study effects of simultaneous administration of tin (Sn) and selenium (Se) on concentrations of several essential elements, mice were injected with either SnCl2 (ip) or Na2SeO3 (sc), alone or both compounds at a daily dose of 5 mumol/kg each for 12 consecutive days. Mice were sacrificed at 20 h after the last injection and concentrations of Sn, Se, Na, Ca, Zn, P, Fe, K, and Mg in the liver, kidney, spleen, pancreas, testis, seminal vesicle, lung, femoral muscle, and femoral bone were determined. In the control mice, Sn and Se concentrations were the highest in bone (0.69 micrograms Sn and 6.93 micrograms Se/g dry wt). Administered Sn was found to accumulate in all organs except the testis. Among the essential elements determined, Na was the most affected in terms of concentration in the organs and Mg was the least affected element in these organs. Among the organs tested, each elemental concentration in the pancreas was most affected. Simultaneous injections of Sn and Se appeared to keep the correlation coefficients between elements similar to those found in the control mice.     

AC1及AC3对白内障形成中晶状体氧化还原物质及硒含量的变化

观察了AC1和AC3对抗亚硒酸钠性白内障形成过程中晶状体的脂类过氧化作用,非蛋白质疏基水平及硒含量。结果表明,亚硒酸钠组大鼠,在晶状体混浊出现前已发生脂类过氧化作用及硒含量的明显增加,非蛋白质巯基含量的显著降低,并持续至核混浊期;而同时接受AC1或AC3的大鼠,晶状体非蛋白质巯基水平初期降低,然后逐渐恢复至正常。AC1可有效的对抗亚硒酸钠所致的脂类过氧化作用增加,而AC3的对抗效应需一定剂量及时程,两者对晶状体硒含量均无明显影响。     

Effects of excess dietary selenite on lead toxicity in sheep

The hypothesis that excess dietary selenite ameliorates lead (Pb) toxicosis in domestic sheep was tested. Twenty 6–8-yr-old ewes fed alfalfa pellets were assigned to the following treatments: (1) control; (2) 9.8 mg Pb/kg body weight (b.w.)/d as PbCO₃; (3) 3 mg Se/animal/d as Na₂SeO₃·5H₂O; or (4) a combination of treatments 2 and 3. The gelatin-encapsulated salts were given orally. The study was terminated on d 104, by which time three animals in the Pb group and all five animals in the Pb+Se group had died. All remaining animals were slaughtered on d 104. Lead and Se concentrations were determined in six biweekly-collected blood samples and in soft tissues and bone. Sheep on the control and Se treatments had similar feed intakes, body weights, and tissue Pb levels. Those in the Pb+Se group had lower feed intake, but higher blood Pb values compared with the Pb group. Feeding either element increased (P<0.05) the concentration of that element in blood, kidney, liver, spleen, and bone. Muscle-Pb concentrations were not affected (P<0.05) by treatment. Selenium concentrations in kidney, liver, and muscle were greater (P<0.05), whereas those in heart were less (P<0.05) for the Pb+Se group than for the Se Group. Clinical signs associated with Pb toxicosis noted in other animals were not observed in the poisoned sheep in this study. Selenite did not protect sheep against Pb toxicity and likely served as a synergistic factor.     

Effects of inorganic selenium compounds on oxidative DNA damage

Exposure of Escherichia coli or mammalian cells to H2O2 results in cell death due to iron-mediated DNA damage. Since selenium compounds have been examined for their ability to act as antioxidants to neutralize radical species, and inorganic selenium compounds are used to supplement protein mixes, infant formula, and animal feed, determining the effect of these compounds on DNA damage under conditions of oxidative stress is crucial. In the presence of Fe(II) and H2O2, the effects of Na2SeO4, Na2SeO3, SeO2 (0.5-5000 microM), and Na2Se (0.5-200 microM) on DNA damage were quantified using gel electrophoresis. Both Na2SeO4 and Na2Se have no effect on DNA damage, whereas SeO2 inhibits DNA damage and Na2SeO3 shows antioxidant or pro-oxidant activity depending on H2O2 concentration. Similar electrophoresis experiments with [Fe(EDTA)](2-) (400 microM) and Na2SeO3 or SeO2 show that metal coordination by the selenium compound is required for antioxidant activity. In light of these results, Na2SeO4 may be safer than Na2SeO3 for nutritional supplements.     

硒对红细胞膜稳定作用的浓度依赖性

 Na_2SeO_3对人红细胞膜骨架具有稳定作用,但这种作用依赖于Na_2SeO_3的浓度。在低离子强度下,4℃透析人红细胞膜,实验组加入不同浓度的Na_2SeO_3,对照组不加Na_2SeO_3。结果表明,0.1—0.8ppm Na_2SeO_3的存在比对照组具有较高的Na~+,K~+-ATP酶活性、膜脂流动性。用N-[3-芘]-马来酰胺作探针,反映两者构象也有差异。如果在透析液中加入较高浓度的Na_2SeO_3(>1.0ppm)则会产生与低浓度相反的结果。人红细胞膜~31P-NMR的测试也表明,加入0.4ppm与4.0ppm Na_2SeO_3会产生不同的结果。与对照组相比较,低浓度使化学位移各向异性值(△σ)下降,而高浓度则使△σ增加。     

Reduction of postoperative lymphedema after oral tumor surgery with sodium selenite

The objective of this double-blind, randomized study was to establish whether sodium selenite administered orally or intravenously reduces postoperative lymphedema after oral tumor surgery and to study the effect of sodium selenite on glutathione peroxidase (GPX) activity and oxygen radical production. Twenty patients were enrolled in the study. Each of the participants received 1000 μg sodium selenite intravenously or orally daily for 3 wk during the pre-, intra-, and postoperative period. The extent of lymphedema was measured for 2 wk and the plasma and whole-blood selenium concentration, GPX, reactive oxygen species (ROS), NO, and malonic dialdehyde were measured for 1 yr postoperatively. There was an inverse correlation between the severity of the lymphedema and the wholeblood/plasma selenium concentration and GPX activity. In addition, a positive correlation between the ROS concentration and the extent of lymphedema was observed. A significant reduction of lymphedema occurred in the sodium selenite-treated group. It is concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema in surgically treated patients with tumors in the oral and maxillofacial areas. Treatment with sodium selenite is especially advantageous as it can be instituted immediately after surgery prior to wound healing when manual lymphatic decongestion therapy cannot be applied.     

Tissue and concentration-dependent effects of sodium selenite on muscle contraction

In this study, we demonstrated that sodium selenite with high doses (≥ 10^-3 M) were potent in inducing a contracture type effect on heart and smooth muscles. Selenite (Se), at a concentration of 10^-3 M, caused a contracture effect in heart preparations. Also, low Se concentrations did not have any significant effect. Although low concentrations of Se (≥ 10^-5 M) had a biphasic effects on acetylcholine (ACh) induced and spontaneous ileum contractions, 10^-3 M selenite enhanced once more a contracture effect similar to that of the heart preparations. Replacing Ca²⁺ concentration of the bathing solution by twofold Ca²⁺ or Ca²⁺-free did not change the effects of selenite (10^-5 M) on contractility of ileum preparations. In vascular smooth muscle, low concentration of selenite (<10^-4) had no significant effects on KC1, and phenylephrine-induced contractions and acethylcholineinduced endothelium-dependent relaxations of isolated rabbit aorta. However, the contractions induced by phenylephrine and the relaxations induced by acetylcholine in rabbit aorta were depressed significantly by high concentration of selenite (10^-3 M). The results obtained by selenite exposure from these three different types of tissue preparations first suggest that the high concentration of selenite exposure induces some alterations in the functions of muscles and endothelium in a tissue and dose-dependent manner. Second, this observed irreversible type of dysfunction of tissues induced by l0^-3 M selenite is not directly dependent on the Ca²⁺ entrance into the cytosol, but might be induced by the increase of intracellular Ca²⁺ with the disturbance of Ca²⁺ regulation.