Toenail selenium as an indicator of environmental exposure: A cross-sectional study.

The relation between toxicity and essentiality of selenium (Se) is of growing interest in human health, as the effects may widely differ depending of its different chemical species and the exposure levels. Toenail Se has been proposed as a reliable biomarker of long-term Se exposure, but few studies investigated the correlation between its toenail content and environmental determinants (i.e., dietary food intake). We aimed to determine the relation of toenail Se levels with serum Se species as well as food items. We recruited a random sample of Modena (Northern Italy) municipal residents, from whom we collected detailed personal information, dietary habits, toenail specimen for Se determination and a blood sample for serum Se speciation analysis. Toenail Se mean value was 0.96 µg/g (range, 0.47­1.60), with slightly higher levels in females, in non-obese subjects and in Se supplements users, while it was lower in current smokers. Toenail Se positively correlated with organic Se forms, mainly selenoprotein P and selenocysteine, and inversely with the inorganic forms (selenite and selenate). Toenail Se was not associated with meat, cereals and dairy products consumption, positively correlated with fruit and slightly with vegetable intake, and negatively with fish and seafood consumption. Finally, no clear association emerged with estimated air Se exposure.

Effect of organic and inorganic selenium supplementation on semen quality and blood enzymes in buffalo bulls.

The present study aimed to evaluate the effect of organic and inorganic selenium (Se) supplementation on semen quality and blood serum profiles of buffalo bulls. Nine mature buffalo bulls were divided into three groups: control (non-supplemented); organic Se (10 mg Sel-Plex®/head twice weekly) and inorganic Se (10 mg sodium selenite/head twice weekly). Semen was collected twice a week for 3 months during Se supplementation. Semen properties were evaluated from fresh ejaculate. Moreover, fructose concentration, aspartate and alanine transaminase (AST and ALT) activities, total protein and total cholesterol were assayed in seminal plasma. Additionally AST, ALT, testosterone and Se levels were determined in the blood serum. Results showed that Se supplementation significantly (P < 0.05) influences the semen parameters during 3 months of treatment. Organic Se significantly (P < 0.05) increased the percentage of viable sperms compared to inorganic Se and the control group. Fructose concentration was significantly higher (P < 0.05) in the seminal plasma of organic Se-treated bulls. Serum testosterone and Se concentrations were significantly (P < 0.05) increased in the Se supplemented groups than the control group. In conclusion, Se supplementation improved the parameters of buffalo bull semen and more precisely, organic Se was more effective for the improvement of semen quality and some blood components than inorganic Se.

Blood Clearance, Distribution, Transformation, Excretion, and Toxicity of Near-Infrared Quantum Dots Ag2Se in Mice.

As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 µmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.

Biodistribution and Pharmacokinetic Study of 3,3' Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice.

BACKGROUND AND OBJECTIVES: 3,3' Diseleno dipropionic acid (DSePA), a synthetic compound has been shown to have radioprotective activity, especially as a lung radioprotector. In this study, the pharmacokinetics and biodistribution of DSePA in MX-1 tumour bearing SCID mice were evaluated. METHODS: Twenty SCID mice were administered DSePA (50 mg/kg bodyweight) by oral gavage following which four animals each were sacrificed at 15, 30 min, 1, 2 and 4 h. Blood and tissue samples were collected for determination of DSePA concentration by graphite furnace atomic absorption spectrometry (GFAAS) method. The control group (n = 4) was administered sterile water and sacrificed at 4 h. RESULTS: Peak plasma concentration (C max) of 2.7 µg/ml was observed at 15 min which returned to near baseline (baseline = 0.6 µg/ml) at 1 h following drug administration. Biphasic pharmacokinetics characterized by rapid distribution phase and a slower elimination phase were observed. Highest maximal concentration (C max) of the drug was observed in lung (19.2 µg/g at 30 min) followed by intestine (14.64 µg/g at 15 min) and kidney (12.96 µg/g at 15 min). There was negligible uptake in tumor tissue and no uptake in brain. CONCLUSIONS: DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.

Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene.

BACKGROUND: Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans. OBJECTIVE: This study aimed to elucidate the human metabolism of selenium to TMSe. DESIGN: Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status [median urinary selenium (U-Se): 6.4 µg/L in mothers, 14 µg/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 µg/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction. RESULTS: TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted ∼10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-µg U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts. CONCLUSIONS: There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.

Evaluation of the efficacy of 2-hydroxy-4-methylselenobutanoic acid on growth performance and tissue selenium retention in growing pigs.

The aim of this study was to compare the efficacy of a new organic Se (2-hydroxy-4-methylselenobutanoic acid [HMSeBA]) source (SO) with sodium selenite (SS) and selenized yeast (SY) at various dietary levels for growth performance and tissue Se deposition in growing pigs. A total of 112 crossbred (Pietrain × [Large White × Landrace]) gilts were allotted at an average body weight of 26.73 kg to 7 dietary treatments with 8 replicate pens of 2 pigs per pen. Pigs were fed basal diets unsupplemented or supplemented either with SS, SY, or SO each at 0.1 or 0.3 mg Se/kg of diet for 32 d. Feed intake and BW were recorded during the experimental period. At the end of the experiment, blood, liver, and psoas major muscle of all gilts were collected for total Se and relative bioavailability determination. No differences were observed on final BW, ADG, ADFI, and G:F among dietary treatments. All Se-supplemented groups exhibited greater total Se contents in plasma (P < 0.01) and liver (P < 0.01) compared with unsupplemented control group. However, Se retention in psoas major muscle was improved only when organic Se source (SY or SO) was added to diets (P < 0.01). Regardless the Se level, the Se deposition in muscle was greater (P < 0.01) in pigs supplemented with SO than those supplemented with SY. Slope ratio assay confirmed the greater bioavailability of Se from organic compared with inorganic Se and also revealed that the relative bioavailability of Se from HMSeBA for plasma, liver, and muscle Se response was 170, 141, and 162%, respectively, for SY. This study shows a potential advantage of HMSeBA supplementation in the increase of Se contents in pig tissues, indicating that this new organic Se source could be an alternative source of Se in swine nutrition.

Organic and inorganic selenium: II. Transfer efficiency from ewes to lambs.

Adequate Se transfer from ewes to lambs is important to prevent Se-deficiency diseases. To evaluate how different chemical forms of Se administered at comparative dosages to mature ewes affect Se status of their lambs, 240 ewes were divided into 8 treatment groups (n = 30 each) and drenched weekly (at an amount equal to their summed daily intake) with no-Se (controls); at recommended amounts (4.9 mg of Se/wk) with inorganic Na-selenite, inorganic Na-selenate, or organic Se-yeast; or at supranutritional amounts (14.7 and 24.5 mg of Se/wk) with Na-selenite or Se-yeast for 1 yr. Weekly drenching of Se was effective at increasing (P < 0.002) Se concentrations in ewe colostrum and milk at 30 d of lactation and in improving (P < 0.001) the Se status of lambs (whole-blood and serum-Se concentrations at birth, and skeletal-muscle Se concentrations at 14 d of age). Selenium concentrations in lacteal secretions were greater in ewes drenched with Se-yeast (colostrum: 374, 436, and 982 ng/mL at 4.9, 14.7, and 24.5 mg of Se/wk, respectively; milk: 26, 39, 64 ng/mL) compared with ewes drenched with Na-selenite (colostrum: 204, 334, 428 ng/mL; milk: 16, 21, 24 ng/mL), and were also greater (P < 0.001) in their lambs. Selenium concentrations continued to increase (P < 0.001) in lamb whole blood (558 and 695 ng/mL at 14.7 and 24.5 mg of Se/wk, respectively), serum (126, 183 ng/mL), and skeletal muscle (991, 1,696 ng/mL) with supranutritional concentrations of Se-yeast, whereas Se concentrations did not differ in whole blood (304, 332 ng/mL), serum (77, 85 ng/mL), or skeletal muscle (442, 482 ng/mg) of lambs from ewes drenched with 14.7 or 24.5 mg of Se/wk of Na-selenite. We conclude that weekly oral drenching of ewes during gestation and lactation with organic Se-yeast results in a more efficient transfer of Se (over a wide range of supplementation rates) from ewe to lamb than does inorganic Na-selenite.

Organic and inorganic selenium: I. Oral bioavailability in ewes.

Although the essentiality of dietary Se for sheep has been known for decades, the chemical source and Se dosage for optimal health remain unclear. In the United States, the Food and Drug Administration (FDA) regulates Se supplementation, regardless of the source of Se, at 0.3 mg of Se/kg of diet (as fed), which is equivalent to 0.7 mg of Se/d or 4.9 mg of Se/wk per sheep. The objectives of this study were to evaluate the effects of Se source (inorganic vs. organic) and supplementation rate (FDA vs. supranutritional rates of 14.7 and 24.5 mg of Se/wk) on whole-blood (WB) and serum-Se concentrations. Mature ewes (n = 240) were randomly assigned to 8 treatment groups (n = 30 each) based on Se supplementation rate (4.9, 14.7, and 24.5 mg of Se•wk(-1)•sheep(-1)) and source [Na-selenite, Na-selenate (4.9 mg/wk only), and organic Se-yeast] with a no-Se control group (0 mg of Se/wk). Treatment groups were balanced for healthy and footrot-affected ewes. For 1 yr, ewes were individually dosed once weekly with 0, 4.9, 14.7, or 24.5 mg of Se, quantities equivalent to their summed daily supplementation rates. Serum- and WB-Se concentrations were measured every 3 mo in all ewes; additionally, WB-Se concentrations were measured once monthly in one-half of the ewes receiving 0 or 4.9 mg of Se/wk. Ewes receiving no Se showed a 78.8 and 58.8% decrease (P < 0.001) in WB- (250 to 53 ng/mL) and serum- (97 to 40 ng/mL) Se concentrations, respectively, over the duration of the study. Whole-blood Se decreased primarily during pregnancy (-57%; 258 to 111 ng/mL) and again during peak lactation (-44%; 109 to 61 ng/mL; P < 0.001). At 4.9 mg of Se/wk, Se-yeast (364 ng/mL, final Se concentration) was more effective than Na-selenite (269 ng/mL) at increasing WB-Se concentrations (P < 0.001). Supranutritional Se-yeast dosages increased WB-Se concentrations in a dose-dependent manner (563 ng/mL, 14.7 mg of Se/wk; 748 ng/mL, 24.5 mg of Se/wk; P < 0.001), whereas WB-Se concentrations were not different for the Na-selenite groups (350 ng/mL, 14.7 mg of Se/wk; 363 ng/mL, 24.5 mg of Se/wk) or the 4.9 mg of Se/wk Se-yeast group (364 ng/mL). In summary, the dose range whereby Se supplementation increased blood Se concentrations was more limited for inorganic Na-selenite than for organic Se-yeast. The smallest rate (FDA-recommended quantity) of organic Se supplementation was equally effective as supranutritional rates of Na-selenite supplementation in increasing WB-Se concentrations, demonstrating the greater oral bioavailability of organic Se.

Simultaneous analysis of mercury and selenium species including chiral forms of selenomethionine in human urine and serum by HPLC column-switching coupled to ICP-MS.

The simultaneous speciation of elements is of great concern, especially in the study of the interactions of species in living organisms. Here we report a method based on the coupling of HPLC-ICP-MS that is capable of separating and analyzing different selenium and mercury species (Se-methylselenocysteine, selenite, selenate, L-selenomethionine, D-selenomethionine, methylmercury and inorganic mercury). The proposed method uses two different mobile phases that are suitable for selenium and mercury speciation and leads to a successful determination of all the species in less than 27 min with good efficiency and resolution. The method was efficiently applied for simultaneous speciation of mercury and selenium in urine and in serum, the latter from umbilical cord samples. Selenocystine has been successfully identified in the former sample. Detection limits obtained were between 0.30 and 2.46 ng. Recovery studies of samples spiked with all species were performed to check the reliability of the method, and satisfactory recoveries (93-110%) were obtained in all cases. The relative standard deviations (RSDs) for species with ten replicate determinations of 80 µg L(-1) were between 4.5 and 9.2%. The proposed method offers a deeper insight into selenium and mercury interactions in the human body.

Identification of a novel selenium-containing compound, selenoneine, as the predominant chemical form of organic selenium in the blood of bluefin tuna.

A novel selenium-containing compound having a selenium atom in the imidazole ring, 2-selenyl-N(alpha),N(alpha),N(alpha)-trimethyl-L-histidine, 3-(2-hydroseleno-1H-imidazol-5-yl)-2-(trimethylammonio)propanoate, was identified from the blood and other tissues of the bluefin tuna, Thunnus orientalis. The selenium-containing compound was purified from the tuna blood in several chromatographic steps. High resolution mass spectrometry and nuclear magnetic resonance spectroscopy showed that the exact mass of the [M+H](+) ion of the compound was 533.0562 and the molecular formula was C(18)H(29)N(6)O(4)Se(2). Its gross structure was assigned as the oxidized dimeric form of an ergothioneine selenium analog in which the sulfur of ergothioneine is replaced by selenium. Therefore, we named this novel selenium-containing compound "selenoneine." By speciation analysis of organic selenium compounds using liquid chromatography inductively coupled plasma mass spectrometry, selenoneine was found widely distributed in various tissues of the tuna, with the highest concentration in blood; mackerel blood contained similar levels. Selenoneine was measurable at 2-4 orders of magnitude lower concentration in a limited set of tissues from squid, tilapia, pig, and chicken. Quantitatively, selenoneine is the predominant form of organic selenium in tuna tissues.

Organic selenium supplementation increased selenium concentrations in ewe and newborn lamb blood and in slaughter lamb meat compared to inorganic selenium supplementation.

BACKGROUND: Selenium is part of the antioxidant defence system in animals and humans. The available selenium concentration in soil is low in many regions of the world. The purpose of this study was to evaluate the effect of organic versus inorganic selenium supplementation on selenium status of ewes, their lambs, and slaughter lambs. METHODS: Ewes on four organic farms were allocated five or six to 18 pens. The ewes were given either 20 mg/kg inorganic selenium as sodium selenite or organic selenium as selenized nonviable yeast supplementation for the two last months of pregnancy. Stipulated selenium concentrations in the rations were below 0.40 mg/kg dry matter. In addition 20 male lambs were given supplements from November until they were slaughtered in March. Silage, hay, concentrates, and individual ewe blood samples were taken before and after the mineral supplementation period, and blood samples were taken from the newborn lambs. Blood samples from ewes and lambs in the same pens were pooled. Muscle samples were taken from slaughter lambs in March. Selenium concentrations were determined by atomic absorption spectrometry with a hydride generator system. In the ANOVA model, selenium concentration was the continuous response variable, and selenium source and farm were the nominal effect variables. Two-sample t-test was used to compare selenium concentrations in muscle samples from the slaughtered lambs that received either organic or inorganic selenium supplements. RESULTS: In all ewe pens the whole blood selenium concentrations increased during the experimental period. In addition, ewe pens that received organic selenium had significantly higher whole blood selenium concentrations (mean 0.28 microg/g) than ewe pens that received inorganic selenium (mean 0.24 microg/g). Most prominent, however, was the difference in their lambs; whole blood mean selenium concentration in lambs from mothers that received organic selenium (mean 0.27 microg/g) was 30% higher than in lambs from mothers that received inorganic selenium (mean 0.21 microg/g). Slaughter lambs that received organic selenium had 50% higher meat selenium concentrations (mean 0.12 mg/kg wet weight) than lambs that received inorganic selenium (mean 0.08 mg/kg wet weight). CONCLUSION: Organic selenium supplementation gave higher selenium concentration in ewe and newborn lamb blood and slaughter lamb meat than inorganic selenium supplementation.

Selenium intake and cardiovascular risk: what is new?

PURPOSE OF REVIEW: Selenium is an essential element with a narrow safety margin. Adequate selenium intake is needed to maximize the activity of glutathione peroxidases and other selenoproteins. This review discusses recent experimental and epidemiologic contributions on the role of selenium for the prevention of atherosclerotic cardiovascular disease. RECENT FINDINGS: Few randomized trials have evaluated the efficacy of selenium supplementation on cardiovascular endpoints. Most trials, conducted in selenium-replete populations, found no evidence of cardiovascular protection. A meta-analysis of 13 prospective cohort studies found a moderate inverse relationship between plasma/serum selenium and coronary heart disease. The interpretation of these data is complicated, however, by potential residual confounding and publication bias. In contrast, recent data from trials of selenium-containing supplements and from epidemiologic studies suggest that chronically increased selenium intake in selenium-replete populations can induce diabetes and maybe also hypercholesterolemia. SUMMARY: Current evidence is insufficient to support a protective role for selenium in cardiovascular prevention. Large high-quality randomized controlled trials and observational studies are needed across populations with different levels of selenium intake. Furthermore, subjects living in regions with high selenium intake should be aware that selenium supplements may increase their risk of diabetes and hypercholesterolemia.

Availability and metabolism of 77Se-methylseleninic acid compared simultaneously with those of three related selenocompounds.

Nutritional selenocompounds are considered to be transformed into the common intermediate selenide for utilization as selenoenzymes and/or for excretion as selenosugar and trimethylselenonium (TMSe). Therefore, selenocompounds can only be traced with a labeled selenium atom. Methylseleninic (MSA(IV)) has been proposed to be a third nutritional selenium source, the other two being inorganic selenocompounds and organic selenoamino acids, and to be a proximate selenochemical for producing the assumed biologically active form methylselenol. Here we applied a new tracer method to compare the availability and metabolism of MSA(IV) with those of three related selenocompounds under exactly identical host and tracing conditions. (82)Se-Selenite, (78)Se-selenate, (77)Se-MSA(IV) and (76)Se-methylselenonic acids (MSA(VI)) were simultaneously administered orally, each at the dose of 25 microg Se/kg body weight, to rats that had been depleted of endogenous natural abundance selenium with a single stable isotope ((80)Se). Time-related changes in the concentrations and/or distributions of the four labeled isotopes in the serum, liver, kidney, pancreas, lung and urine were determined simultaneously by inductively coupled argon plasma mass spectrometry (ICP MS) and/or HPLC-ICP MS. The availability with different isotope ratios was in the decreasing order of selenate>selenite=MSA(IV)>MSA(VI). Although selenate and MSA(VI) were distributed in organs and urine partly in their intact forms, MSA(IV) and selenite were not detected in the intact forms at all. MSA(IV) and MSA(VI) but not selenite or selenate produced TMSe in organs other than the liver, suggesting the transformation of MSA(IV) into methylselenol, and then either into selenide for the synthesis of selenoproteins and selenosugar or directly into TMSe. Thus, selenosugar and TMSe were produced widely in the organs. However, TMSe was not detected in the liver. The organ- and selenium source-specific production of TMSe was discussed as to the differences in selenium sources, and demethylation and methylation activity.

The determination of total Se in urine and serum by graphite furnace atomic absorption spectrometry using Ir as permanent modifier and in situ oxidation for complete trimethylselenonium recovery.

The present work evaluated the use of iridium (Ir) as permanent modifier for the determination of total selenium in urine and serum by graphite furnace atomic absorption spectrometry. Concerning urine, the presence of trimethylselenonium (TMSe(+)) was especially considered. Pyrolysis and atomization temperatures of 1,000 and 2,100 degrees C, respectively, were used. For nondigested urine and serum samples, 0.2% v/v HNO(3) and Triton X-100 were used as diluents, respectively, and the same initial platform Ir treatment was effective for up to 1,100 atomization cycles. Good precision [less than 5% relative standard deviation (RSD)] can be achieved with the proposed method. Low TMSe(+) recovery was observed for nondigested urine samples. Thus, if this species is to be considered in urine analysis, a previous external mineralization step was found to be necessary. Alternatively, an in situ oxidation treatment was developed. Detection limits of 8, 10, and 7 mug l(-1) were obtained after dilution, microwave-assisted digestion, and in situ oxidation procedures, respectively. The accuracy of the method was validated by the analysis of certified reference or commercial quality control materials and spiked samples.

Analysis of the selenium species distribution in cow blood by size exclusion liquid chromatography-inductively coupled plasma collision cell mass spectrometry (SEC-ICPccMS).

A method for performing rapid semiquantitative screening of the distribution of Se species in the blood of cows fed with a diet enriched in selenized yeast was optimized. The method was based on direct injection of a blood sample onto a high resolution size exclusion chromatographic column and fractionation of the selenium species. Selenium was detected on-line by ICP-MS with a collision cell. The concentrations of selenized haemoglobin and free selenomethionine were estimated using the chromatogram. The method was applied to a study involving 15 control and 15 treated dairy cows at four different supplementation time points. The increase in the selenomethionine and selenized haemoglobin was a linear function of the total selenium concentration. A threshold value of 600 ng ml(-1) of total Se was established beyond which selenomethionine could not be incorporated into the protein. No inorganic selenium was found to be present. The total selenium in cow blood correlated well with that in milk. The selenium supplementation did not change the protein distribution profiles for other essential elements (Cu, Fe, Mn, Zn).

Sodium selenate partially corrects impaired functional responses in detrusor muscle in streptozotocin-induced diabetic rats.

Selenium selenate was administered to streptozotocin-induced diabetic rats to assess its effects on the detrusor muscle. Thirty-two rats were divided into four groups of eight subjects each. The study animals were made diabetic by means of a single intravenous injection of streptozotocin (STZ). The responsiveness of the detrusor was improved in the group injected with sodium selenate. Diabetes caused significant increases in carbachol and beta,gamma-MeATP-evoked contractions and significant decrease of contractions induced by electrical stimulation. Isoprenaline-induced relaxation of the detrusor muscle was diminished by diabetes, whereas ATP relaxation appeared to be increased. Although adenosine-induced relaxations in controls and in diabetic rats were accompanied by unchanged responses in normoxic conditions, a significant enhancement in the detrusor muscle was observed during hypoxia. This enhancement of adenosine responsiveness in hypoxic conditions is inhibited in diabetes. Treatment with sodium selenate prevented alterations of both carbachol-induced contractility and isoprenaline-evoked relaxation, whereas nerve-mediated contractions and purinergic responses were not improved in diabetic rats after treatment. Our data suggest that changes in cholinergic and adrenergic responses were the result of selenium deficiency in diabetic rats.

Determination of selenium in serum by FI-HG-AAS and calculation of dietary intake.

A method was developed for the determination of selenium concentration in serum by flow injection-hydride generation-atomic absorption spectrometry (FI-HG-AAS) following microwave digestion of serum samples and reduction of selenate to selenite. The detection limit of the method was 0.3 microg Se/L and the characteristic concentration, corresponding to the 0.0044 absorbance signal, was 0.12 microg Se/L. The results from the analysis of two Seronorm standard reference materials showed good agreement with the certified values. The method was then used to analyze selenium in sera of Austrian and Slovenian people for the calculation of dietary intakes. The selenium concentrations in sera of mothers at delivery, their neonates, and the male and female adults were 71+/-14, 42+/-6, 75+/-21, and 65+/-16 microg/L for the Austrians and 62+/-15, 34+/-7, 70+/-12, and 66+/-15 microg/L for the Slovenians. The dietary intakes of selenium of the mothers and the male and the female adults were calculated as 52, 37, and 46 microg/d for the Austrians and 45, 38, and 32 microg/d for the Slovenians.

Effects of selenium dioxide on blood and femoral bone marrow of rats.

This study was undertaken to investigate the effects of selenium dioxide (SeO2) on rat blood and femoral bone-marrow oxidant mechanisms. Treatment with SeO2, 67 microg Se/kg i.p. daily for 14 d, significantly decreased lipid peroxidation and the concentrations of Fe in serum and bone marrow. The concentrations of Se in serum and bone-marrow cells were significantly increased after SeO2 treatment. The activities of glutathione peroxidase (GPx) in blood and bone-marrow cells were markedly increased. The levels of oxyhemoglobin in blood were significantly increased, while the concentrations of methemoglobin were decreased after SeO2 administration. The fragility of erythrocytes membranes was significantly decreased in SeO2-treated rats compared to controls. Data suggest that treatment with a low dose of SeO2 may provide antioxidant nutrients to blood and bone marrow.

Speciation of metabolites of selenate in rats by HPLC-ICP-MS.

The metabolic pathway for and metabolites of selenium (Se) administered intravenously to rats in the form of selenate at a dose of 0.3 mg Se kg-1 body weight were studied by speciating Se in the bloodstream, liver and urine by HPLC-inductively coupled argon plasma mass spectrometry. Selenate was not taken up by red blood cells (RBCs) and disappeared from the bloodstream much faster than selenite, without any change in its chemical form before it disappeared from the plasma. Selenium excreted into the urine after the administration of selenate showed different patterns from those of selenite in both amounts and chemical forms. With the selenate group, the concentration of Se in urine was highest at 0-6 h and the chemical species of Se was selenate at 0-6 h; thereafter a monomethylselenol-related Se compound (MMSe*) and trimethylselenonium ions (TMSe) appeared, selenate not being excreted after 6 h. On the other hand, in the selenite group, the concentration of Se peaked at 6-12 h, and the chemical species of Se were MMSe* and TMSe. Selenate was reduced in vitro on incubation in either a liver homogenate or supernatant fraction, although much more slowly than in the whole body. Selenate was not reduced by glutathione or dithiothreitol. The results suggest that in contrast to selenite, which is taken up by and reduced in RBCs, and then transferred to the liver, approximately 20% of the selenate administered to rats was excreted into the urine without any change in its chemical form with the present dose, and the major portion of selenate was taken up by the liver, reduced and then utilized for the synthesis of selenoproteins or excreted into the urine after being methylated.