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PubMed1984

Measurement of trimethylselenonium ion in human urine.

A comparison is made between two methods (ion-exchange chromatography vs a difference method) for the quantitative measurement of trimethylselenonium ion (TMSe) in human urine. It is shown that the difference method yields reliable data only if TMSe constitutes a relatively large fraction of urine selenium. Under normal conditions of selenium intake in man, accurate measurement of this important metabolite can, at present, be carried out only with the ion-exchange chromatographic procedure. Preliminary data from a human subject employing stable isotope tracer methodology are given to show that the fraction of urine selenium present as TMSe varies with the level of intake as well as other factors.

Chemical Phenomena↗
PubMed2001

Selenium and the brain: a review.

Similar to other tissues selenium from selenomethionine is deposited in the brain at higher concentrations than selenium in other forms. Vitamin E has a greater effect than selenium in reducing lipid peroxidation in various brain regions. Selenium does not have as great effect on glutathione peroxidase (GPX) activity in the brain as in most other organs. Prolonged selenium and iodine deficiencies will compromise thyroid hormone homeostatus in the brain and this is due to changes in deiodinases activities and lipid peroxidation. Even though selenium deficiency results in reduced GPX activity and selenium content in the brain, there is no reduction in thioredoxin reductase activity or selenoprotein W levels. Selenoprotein P is taken up in greater amounts by the brain but not by other organs in selenium deficient animals, suggesting a critical function of this selenoprotein in this organ. Selenium will influence compounds with hormonal activity (and neurotransmitters) in the brain, and this is postulated to be the reason selenium affects moods in humans and behavior in animals. Even though selenium counteracts the neurotoxicity of mercury, cadmium, lead and vanadium, it causes them to accumulate in the brain, presumably in a nontoxic complex.

Animals↗
PubMed1979

Complex formation between selenium and methylmercury.

Methylmercury, after incubation at 3k7 degrees C and pH 7.0 with selenite in the presence of rat erythrocytes, can be extracted into benzene as an unstable 2 : 1 complex with selenium. The same complex, possibly bis-methylmercury selenide, is formed when methylmercury is treated with hydrogen selenide at pH 7.0 in the absence of erythrocytes.

Animals↗
PubMed1994

Comparison of the effects of an organic and an inorganic form of selenium on a mammary carcinoma cell line.

The development of new compounds with greater cancer inhibitory activity and that are well tolerated continues to be a priority in chemoprevention research involving selenium. One compound, 1,-4-phenylene-bis(methylene)selenocyanate (p-XSC), is representative of a series of organoselenium compounds with these characteristics. In this study, the effects of p-XSC on a mouse mammary carcinoma cell line were compared to those of sodium selenite, which has been shown to be growth inhibitory. Treatment with p-XSC caused a 3- to 6-fold greater accumulation of selenium within cells than did treatment with equivalent amounts of selenite and cells were able to better tolerate higher cellular levels of selenium derived from p-XSC. Both compounds resulted in a dose-dependent reduction in cell number after 24 h of exposure. Selenite and p-XSC also caused a dose-dependent increase in cell death by apoptosis. This effect was observed within 5 h of treatment. The effect of p-XSC on apoptosis was more pronounced than that of selenite, especially at the 20 microM level of exposure. The induction of apoptosis by selenium compounds may partially account for their chemopreventive activity.

Animals↗
PubMed1989

Phosphoroselenoate oligodeoxynucleotides: synthesis, physico-chemical characterization, anti-sense inhibitory properties and anti-HIV activity.

Oligodeoxynucleotides with a phosphorus atom in which one of the non-bridging oxygen atoms is substituted by selenium were prepared and investigated with respect to their antisense properties. A general synthesis of phosphoroselenoate analogs of oligonucleotides is described using potassium selenocyanate as the selenium donor. The compounds, characterized by 31P NMR, were shown to decompose to phosphate with a half-life of ca. 30 days. Melting temperatures of duplexes between poly(rA) or poly(rI) with oligo(dT) and oligo(dC), respectively, indicate diminished hybridization capability of phosphoroselenoate oligomers relative to both the unmodified phosphodiester oligomers and the phosphorothioate congeners. A phosphoroselenoate 17-mer is a sequence specific inhibitor of rabbit beta-globin synthesis in wheat germ extract and in injected Xenopus oocytes. In contrast phosphoroselenoate analogs are potent non-sequence specific inhibitors in rabbit reticulocyte lysate. In vitro HIV assays were carried out on a phosphoroselenoate sequence and compared with a phosphorothioate analogue that has previously been shown to exhibit anti-HIV activity (Matsukura et al., Proc. Natl. Acad. Sci. (1987) 84, 7706-7710). The phosphoroselenoate was somewhat less active, and was much more toxic to the cells.

Animals↗
PubMed1983

A comparison of miconazole nitrate and selenium disulfide as anti-dandruff agents.

The anti-dandruff efficacy of two shampoos containing 2% miconazole nitrate and 2.5% selenium disulfide was compared in 15 subjects and eight subjects, respectively. The antifungal drug, miconazole nitrate, was found to possess anti-dandruff activity similar to selenium sulfide, a cytostatic compound. For evaluation, techniques of clinical grading and the corneocyte count were used and the latter was found inaccurate. Instead, clinical assessment by grading the severity, supplemented by cytodiagnosis by smear examination was found more helpful. The latter helps to evaluate both the altered pathophysiologic and microbial factors operating in a given case of dandruff, which is a symptom complex brought about by multiple etiologic factors.

Adolescent↗
PubMed1992

Radioprotection by metals: selenium.

The need exists for compounds that will protect individuals from high-dose acute radiation exposure in space and the agents that might be less protective but less toxic and longer acting. Metals and metal derivatives provide a small degree of radioprotection (dose reduction factor < or = 1.2 for animal survival after whole-body irradiation). Emphasis is placed here on the radioprotective potential of selenium (Se). Both the inorganic salt, sodium selenite, and the organic Se compound, selenomethionine, enhance the survival of irradiated mice (60Co, 0.2 Gy/min) when injected IP either before (-24 hr and -1 hr) or shortly after (+15 min) radiation exposure. When administered at equitoxic doses (one-fourth LD10; selenomethionine = 4.0 mg/kg Se, sodium selenite = 0.8 mg/kg Se), both drugs enhanced the 30-day survival of mice irradiated at 9 Gy. Survival after 10-Gy exposure was significantly increased only after selenomethionine treatment. An advantage of selenomethionine is lower lethal and behavioral toxicity (locomotor activity depression) compared to sodium selenite, when they are administered at equivalent doses of Se. Sodium selenite administered in combination with WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, enhances the radioprotective effect and reduces the lethal toxicity, but not the behavioral toxicity, of WR-2721. Other studies on radioprotection and protection against chemical carcinogens by different forms of Se are reviewed. As additional animal data and results from human chemoprevention trials become available, consideration also can be given to prolonged administration of Se compounds for protection against long-term radiation effects in space.

Aerospace Medicine↗
PubMed1998

Organic and inorganic selenium supplementation to lactating mothers increase the blood and milk Se concentrations and Se intake by breast-fed infants.

The aim of this study was to determine the effect of selenium (Se) supplementation to lactating women on Se concentrations and glutathione peroxidase (GSH-Px) activities in blood components of mothers and breast-fed infants and on milk Se levels and Se intake by breast-fed infants. Lactating mothers were supplied for 3 months with 200 micrograms Se/day in the form of yeast-Se (Y-Se) and sodium selenite. Initial blood and plasma Se levels of all women (n = 67) were 76.6 and 53.2 micrograms/L, respectively. After 3 months Se concentrations both in whole blood and in plasma from mothers and infants were significantly higher than the initial values. Y-Se exerts a stronger effects than selenite on blood and plasma Se levels. Initial milk Se concentration was 8.9 micrograms/L and after 1 month in both groups in reached a plateau at 14-16 micrograms/L. This resulted in an increase of Se intake in breast-fed infants from 6.1 to a plateau of 11-13 micrograms Se/day. GSH-Px activities in plasma and red cells of Y-Se group increased significantly and reached a plateau after 1 and 2 months, respectively, while in the selenite group the enzyme activities increased steadily throughout the entire period of the study. Selenite exerts a stronger effect on GSH-Px both in maternal and in infant blood components as compared with Y-Se. In milk the GSH-Px activity in the Y-Se group did not change during the study, while in the selenite group after 3 months it increased almost 2-fold compared to the initial value. In conclusion, this study shows that organic Se causes higher Se deposition than did the inorganic form.

Adult↗
PubMedDate not supplied

The relationship between gamma-glutamyl transpeptidase and Hg levels in Se/Hg antagonism in mouse liver and kidney.

The gamma-glutamyl transpeptidase (gamma-GT) activity and Hg concentrations were studied in Se/Hg antagonism in mouse liver and kidney after treatment with methyl mercury (MM) (MM group) and MM + sodium selenite (SE) (SM group). In acute treatment (dietary doses: MM = 250 p.p.m.; SE = 90 p.p.m.; length of treatment 11 days), hepatic gamma-GT activity increased in both protected and unprotected animals with respect to controls and reached a peak after 3 days with respect to controls, its value being relatively greater in the MM group. On the contrary, renal gamma-GT decreased with time with respect to controls and was higher in the SM group at 3 and 7 days. Liver and kidney accumulation of Hg increased and decreased respectively with time, and was higher in SM groups in most cases. In chronic treatment (dietary doses: MM = 12.5 p.p.m.; SE = 9 p.p.m.; length of treatment 12 months) hepatic gamma-GT activity in the MM group was higher than in the SM group at 1.5 and 7 months, whereas the renal activity was lower at 7 months and unchanged at 1.5 and 12 months. In comparison with the acute treatment, the trend of Hg accumulation was similar in liver and different in kidney; Hg concentrations of the SM group were always greater than those of the MM group. Glutathione (GSH) in liver and non-protein SH groups (NPSH) in kidney were also measured in acutely treated animals. On the first day GSH was about 50% of the control value in both the MM and SM groups; it subsequently remained constant in the MM group, but increased to a peak at 7 days, without reaching the control value, in the SM group. Unlike the liver, renal NPSH increased in both groups on the first day, and then decreased with time without reaching the control value, SM group values always exceeding those of MM group. The modulation of gamma-GT activity in liver and kidney caused by SE suggests that the enzyme plays a role in Hg accumulation.

Animals↗
PubMed1990

Mechanism of the reaction of ebselen with endogenous thiols: dihydrolipoate is a better cofactor than glutathione in the peroxidase activity of ebselen.

The therapeutic effect of ebselen has been linked to its peroxidase activity. In the present study, the peroxidase activity of ebselen toward H2O2 with the endogenous thiols GSH and dihydrolipoate [L(SH)2] as cofactors was determined. When GSH was used, peroxide removal was described by a ter uni ping pong mechanism with Dalziel coefficients for GSH and H2O2 of 0.165 +/- 0.011 and 0.081 +/- 0.005 mM min, respectively. When L(SH)2 was used, peroxidase activity was independent of the concentration of L(SH)2 in the concentration range studied (5 microM to 2 mM) and peroxide removal was only dependent on the concentration of H2O2 and ebselen, with the second-order rate constant being 12.3 +/- 0.8 mM-1 min-1. To elucidate the difference between GSH and L(SH)2, the molecular mechanism of the peroxidase activity of ebselen was investigated, using UV spectrophotometry, high pressure liquid chromatography, 77Se NMR, and mass spectrometry. GSH was found to react quickly with ebselen to give a selenenyl sulfide, an adduct of GSH to ebselen. Subsequently, the GSH-selenenyl sulfide is converted into the diselenide of ebselen. Finally the diselenide reacts with a peroxide and ebselen is regenerated. The formation by GSH of the diselenide from the GSH-selenenyl sulfide of ebselen is slow and linearly dependent on the concentration of free thiol; however, no net consumption of GSH was observed. Furthermore, it is likely that a selenol is an intermediate in diselenide formation. After reaction between ebselen and L(SH)2 the diselenide of ebselen was immediately detected. The fast formation of the diselenide with L(SH)2 versus the slow formation of the diselenide with GSH accounts for our observation that L(SH)2 is a better cofactor than GSH in the peroxidase activity of ebselen. Our results suggest that the interaction between ebselen and L(SH)2 might be of major importance in the mechanism by which ebselen exerts its therapeutic effect.

Azoles↗
PubMed2006

Absorption of selenium by Lactuca sativa as affected by carboxymethylcellulose.

Several organic compounds of high molecular weight present in soil interact with selenium and may act as active binding agents affecting its availability in soil, and, consequently, selenium uptake by plants. This study is aimed at investigating the effects of polysaccharides on selenium speciation in soil and on selenium absorption by Lactuca sativa L. plants. Three-week-old seedlings were transplanted into pots filled with soil, and sodium selenite at rates of 1.5 and 5mgSekg(-1) of soil, or sodium selenate at a rate of 1.5mgSekg(-1) of soil were applied. Carboxymethylcellulose (CMC) was added to the soil at rates of 0, 3 and 30mgkg(-1) of soil. After 48 and 110d from transplanting plants were harvested, separated into root and shoot, and fresh and dry matter weights were recorded. Total selenium was determined in both soil and plant samples. A sequential extraction was used to investigate the different Se oxidation states and assess the availability of Se in soil after the final harvesting. Both selenite and selenate were absorbed by roots, but plants amended with Se(VI+) showed higher selenium concentration than plants amended with Se(IV+). Selenite appears to be less mobile than selenate both in soil and plants. The addition of carboxymethylcellulose to soil decreased the amount of selenium absorbed by plants. CMC interacted with Se, making it less mobile as evidenced by the increase in the insoluble fractions. The insoluble Se forms in soil may represent environmental Se sinks potentially available for plants if the substrate is re-used for subsequent growth cycles and selenium species are mobilized as a result of biological and chemical processes.

Carboxymethylcellulose Sodium↗
PubMed2003

Identification of selenium species in urine by ion-pairing HPLC-ICP-MS using laboratory-synthesized standards.

This study focused on the detection/identification of possible selenium metabolites in human urine. Organoselenium compounds not commercially unavailable were synthesized and characterized by electrospray mass spectrometry. Separation of selenomethionine, methylselenomethionine, trimethylselonium, selenoethionine, and selenoadenosylmethionine was achieved by ion-pairing HPLC with a mobile phase of 2 mmol L(-1) hexanesulfonic acid, 0.4% acetic acid, 0.2% triethanolamine (pH 2.5), and 5% methanol. The column effluent was introduced on-line to inductively coupled plasma-mass spectrometry for selenium-specific detection ((77)Se and (78)Se). For selenium speciation in urine, solid-phase extraction was carried out using C(18) cartridges modified with hexanesulfonic acid. Selective retention of cationic species was observed from acidified urine (perchloric acid, pH 2.0). After elution with methanol, evaporation, and dissolution in the mobile phase, the sample was introduced to the HPLC-ICP-MS system and the chromatographic peaks were assigned by adding standards. The species identified in urine were selenomethionine, trimethylselonium ion, and selenoadenosylmethionine. The last species was detected for the first time and our results suggest that selenomethionine might enter the metabolic pathway of its sulfur analog in the activated methylation cycle.

Chromatography, High Pressure Liquid↗
PubMed1987

Enzymatic methylation of sulfide, selenide, and organic thiols by Tetrahymena thermophila.

Cell extracts from the ciliate Tetrahymena thermophila catalyzed the S-adenosylmethionine-dependent methylation of sulfide. The product of the reaction, methanethiol, was detected by a radiometric assay and by a gas-chromatographic assay coupled to a sulfur-selective chemiluminescence detector. Extracts also catalyzed the methylation of selenide, and the product was shown by gas chromatography-mass spectrometry to be methaneselenol. The sulfide and selenide methyltransferase activities copurified with the aromatic thiol methyltransferase previously characterized from this organism (A.-M. Drotar and R. Fall, Pestic. Biochem. Physiol. 25:396-406, 1986), but heat inactivation experiments suggested the involvement of distinct sulfide and selenide methyltransferases. Short-term toxicity tests were carried out for sulfide, selenide, and their methylated derivatives; the monomethylated forms were somewhat more toxic than the nonmethylated or dimethylated compounds. Cell suspensions of T. thermophila exposed to sulfide, methanethiol, or their selenium analogs emitted methylated derivatives into the headspace. These results suggest that this freshwater protozoan is capable of the stepwise methylation of sulfide and selenide, leading to the release of volatile methylated sulfur or selenium gases.

Animals↗
PubMed2001

[Direct determination of selenium and bismuth in antimony and antimony compound by hydride generation-atomic fluorescence spectrometry].

The interference of Sb in determination of Se and Bi in antimony powder and antimony compound has been studied in different acidity, it is found that the interference of antimony has been reduced apparently in high acidity. Simultaneously, according to the difference of hydride generation reaction between Sb5+ and Sb3+, a sensitive and rapid method has been developed and used to determine Se and Bi in real samples. The recovery of the method is 95%-105% for practical samples. Detection limits are 0.00004 x 10(-2) (content) for Se and 0.0001 x 10(-2) mg.L-1 (content) for Bi respectively. The relative standard deviations of Se are 2.4% (content = 0.00169 x 10(-2) mg.L-1) and 5.4% (content = 0.00056 x 10(-2) mg.L-1). The relative standard deviations of Bi are 5.0% (content = 0.00024 x 10(-2) mg.L-1) and 1.3% (content = 0.00229 x 10(-2) mg.L-1). The method has been applied to determination of Se and Bi in practical samples with satisfactory results.

Antimony↗
PubMed1987

Metabolism of selenocyanate in the rat.

Rats injected subcutaneously with 2 mg Se/kg body weight of [75Se]selenocyanate or [14C, 75Se]selenocyanate excreted dimethylselenide (DMSe) in the breath and trimethyl-selenonium ion (TMSe) in the urine. The 24-h respiratory DMSe and urinary TMSe excretions were 26.8 +/- 8.1 and 14.5 +/- 5.1% of the dose, respectively. Tissue concentrations of 75Se were highest in the kidneys (1.89 +/- 0.2% dose/g), liver (1.46 +/- 0.2% dose/g), and blood (0.50 +/- 0.05% dose/ml), and lower (greater than 0.3% dose/g) in the other tissues. Trimethyl-selenonium was the major form (61%) of selenium in urine. Approximately 2% of the dose of doubly labeled SeCN- was excreted unchanged in urine (about 12% of urinary Se). 14C from doubly labeled SeCN- was not present in the methylated selenium metabolites, but a major 14C urinary metabolite was identified as thiocyanate. These results indicate that a substantial part of selenocyanate in the body undergoes metabolism and Se is excreted in methylated forms following scission of the C-Se bond.

Animals↗
PubMed1982

Recovery of endogenous selenium from fish tissues by open system dry ashing.

Quantitative recovery of endogenous selenium from fish tissues following dry ashing techniques has not been confirmed. An open system dry ashing procedure, using oxidative fusion with Mg(NO3)2 X 6H2O in the presence of MgO, was tested for recovery of selenium from National Bureau of Standards (NBS) Reference Materials (tuna and oyster) and selected fish tissues. Recovery after dry ashing and hydride analysis was complete from NBS Bovine Liver, Tuna, and Oyster Tissues, as well as from Food and Drug Administration cod, haddock, perch, and flounder research materials. Endogenous selenium, injected into rainbow trout (Salmo gairdneri) as 75Se, was recovered after ashing from liver, ovaries, gastrointestinal tract, muscle, bile, and carcass, 3 and 10 days post-injection. Results indicate that open vessel oxidative fusion is a rapid, simple technique applicable to quantitative recovery of selenium from organoselenium compounds that exist in various aquatic species. The diluted digestate is readily amenable to conventional hydride generation analysis.

Animals↗
PubMedDate not supplied

Tissue-specific clastogenic effects of chromium and selenium salts in vivo.

The clastogenic effects of inorganic compounds of chromium (K2Cr2O7) and selenium (Na2SeO3) on the chromosomes of rat lymphocytes and bone marrow have been investigated. In vitro exposure of rat lymphocytes to K2Cr2O7 gave highly significant and dose-related increases in abnormal metaphases at 6 concentrations from 7 X 10(-6) M to 3.2 X 10(-5) M. Similar in vitro exposure of lymphocytes to Na2SeO3 showed that it was clastogenic at concentrations of 7.5 X 10(-6) M, 1 X 10(-5) M and 2.5 X 10(-5) M. However, with in vivo exposures of K2Cr2O7 (i.p. and i.v.) it was only possible to demonstrate clastogenicity in lymphocytes at sublethal concentrations (36 mg/kg X 2 i.v.) and then only if the results were tested against all controls combined (1900 metaphases, 19 animals). On the other hand, very highly significant clastogenic effects were obtained in bone marrow cells exposed in vivo to K2Cr2O7 at 21 mg/kg i.p. and 12, 18, 24 and 36 mg/kg i.v. In vivo exposure to Na2SeO3, with concentrations up to 6 mg/kg X 2 i.v., caused no significant increase in abnormal metaphases in lymphocytes but 5 and 6 mg/kg X 2 i.v. caused a significant increase in abnormal metaphases in bone marrow. These results suggest that K2Cr2O7 and Na2SeO3 are acting as 'S' dependent chemicals. Although not directly comparable, they are compatible with the warnings given by other authors both on the detection of aberrations in lymphocytes after chronic exposure in man and on short-term testing of lymphocytes at low doses related to human exposure.

Animals↗