Showing papers on "Selenium published in 2006"

Arsenic and selenium in microbial metabolism.

Abstract: Arsenic and selenium are readily metabolized by prokaryotes, par- ticipating in a full range of metabolic functions including as- similation, methylation, detoxification, and anaerobic respiration. Arsenic speciation and mobility is affected by microbes through oxidation/reduction reactions as part of resistance and respiratory processes. A robust arsenic cycle has been demonstrated in diverse environments. Respiratory arsenate reductases, arsenic methyltrans- ferases, and new components in arsenic resistance have been recently described. The requirement for selenium stems primarily from its in- corporation into selenocysteine and its function in selenoenzymes. Selenium oxyanions can serve as an electron acceptor in anaero- bic respiration, forming distinct nanoparticles of elemental selenium that may be enriched in 76 Se. The biogenesis of selenoproteins has been elucidated, and selenium methyltransferases and a respiratory selenate reductase have also been described. This review highlights recent advances in ecology, biochemistry, and molecular biology and provides a prelude to the impact of genomics studies.

Effects of Chemical Form of Selenium on Plasma Biomarkers in a High-Dose Human Supplementation Trial

Abstract: Intervention trials with different forms of selenium are under way to assess the effects of selenium supplements on the incidence of cancer and other diseases. Plasma selenium biomarkers respond to selenium administration and might be useful for assessing compliance and safety in these trials. The present study characterized the effects of selenium supplementation on plasma selenium biomarkers and urinary selenium excretion in selenium-replete subjects. Moderate (approximately 200 microg/d) to large (approximately 600 microg/d) selenium supplements in the forms sodium selenite, high-selenium yeast (yeast), and l-selenomethionine (selenomethionine) were administered. Subjects were randomized into 10 groups (placebo and three dose levels of each form of selenium). Plasma biomarkers (selenium concentration, selenoprotein P concentration, and glutathione peroxidase activity) were determined before supplementation and every 4 weeks for 16 weeks. Urinary selenium excretion was determined at 16 weeks. Supplementation with selenomethionine and yeast raised the plasma selenium concentration in a dose-dependent manner. Selenite did not. The increased selenium concentration correlated with the amount of selenomethionine administered. Neither glutathione peroxidase activity nor selenoprotein P concentration responded to selenium supplementation. Urinary selenium excretion was greater after selenomethionine than after selenite, with excretion after yeast being intermediate and not significantly different from either of the other two. We conclude that plasma selenium concentration is useful in monitoring compliance and safety of selenium supplementation as selenomethionine but not as selenite. Plasma selenium seems to reflect the selenomethionine content of yeast but not the other yeast selenium forms. As judged by urinary selenium excretion, selenium in the form of selenomethionine is better absorbed than selenite.

Both Selenoproteins and Low Molecular Weight Selenocompounds Reduce Colon Cancer Risk in Mice with Genetically Impaired Selenoprotein Expression

Abstract: Selenium has cancer protective effects in a variety of experimental systems. Currently, it is not known whether selenoproteins or low molecular weight selenocompounds are responsible for this activity. To evaluate the contribution of selenoproteins to the cancer protective effects of selenium, we used transgenic mice that carry a mutant selenocysteine transfer RNA gene, which causes reduced selenoprotein synthesis. Selenium homeostasis was characterized in liver and colon of wild-type and transgenic mice fed selenium-deficient diets supplemented with 0, 0.1, or 2.0 microg selenium (as selenite)/g diet. (75)Se-labeling, Western blot analysis, and enzymatic activities revealed that transgenic mice have reduced (P < 0.05) liver and colon glutathione peroxidase expression, but conserved thioredoxin reductase expression compared with wild-type mice, regardless of selenium status. Transgenic mice had more (P < 0.05) selenium in the nonprotein fraction of the liver and colon than wild-type mice, indicating a greater amount of low molecular weight selenocompounds. Compared with wild-type mice, transgenic mice had more (P < 0.05) azoxymethane-induced aberrant crypt formation (a preneoplastic lesion for colon cancer). Supplemental selenium decreased (P < 0.05) the number of aberrant crypts and aberrant crypt foci in both wild-type and transgenic mice. These results provide evidence that a lack of selenoprotein activity increases colon cancer susceptibility. Furthermore, low molecular weight selenocompounds reduced preneoplastic lesions independent of the selenoprotein genotype. These results are, to our knowledge, the first to provide evidence that both selenoproteins and low molecular weight selenocompounds are important for the cancer-protective effects of selenium.

Levels of selenium, zinc, copper, and antioxidant enzyme activity in patients with leukemia.

Abstract: Essential elements, mainly selenium and zinc, were involved in protection against oxidative stress in cells. Oxidation could lead to the formation of free radicals that have been implicated in the pathogenesis of many diseases, including leukemia. Leukemia is a neoplastic disease that is susceptible to antioxidant enzyme and essential elements alterations. This study was undertaken to examine the levels of essential elements, antioxidant enzymes activities, and their relationships with different types of leukemia. Serum selenium, zinc, and copper concentrations, red blood cell glutathione peroxidase (GPx) activities, plasma Cu-Zn superoxide dismutase (Cu-Zn SOD) activities and lipid peroxidation (LPO) levels were determined in 49 patients with different types of leukemia before initial treatment. Serum selenium and zinc concentrations were lower in leukemia patients than those of controls (p<0.01). Serum copper concentration was higher in leukemia patients than that of controls (p<0.01). The activities GPx and Cu-Zn SOD were significantly increased in leukemia patients, especially with acute leukemia (AL), acute lymphoid leukemia (ALL), and acute nonlymphoid leukemia (ANLL) (p<0.05), whereas no difference was found between those of chronic myelogenous leukemia and the controls. The levels of LPO were normal as controls. Serum selenium concentration was not correlated with GPx, and serum levels of zinc and copper were not related to Cu-Zn SOD. Serum zinc levels had a negative correlation with the absolute peripheral blast cells, whereas serum copper had a positive correlation with the absolute peripheral blast cells. Increased GPx and Cu-Zn SOD activities and normal levels of LPO, which were a protective responses, were an indicator of mild oxidative stress; it might indicate that the essentials elements alterations in leukemia patients were mostly dependent on tumor activity. Changes of their levels demonstrated that there are low selenium, zinc, and high copper status in leukemia patients. The decrease of plasma zinc and increase of the Cu/Zn ratio could be the index that showed an unfavorable prognosis of acute leukemia.

Evaluating Selenium Poisoning

Abstract: Selenium poisoning in humans is reviewed from the perspective of the clinical laboratory. While evaluation of selenium poisoning is straightforward when the analytic results are markedly elevated and the patient is acutely symptomatic, distinguishing toxic from non-toxic elevations is a more frequent issue and more challenging. A significant problem is that selenium is determined as its total concentration in spite of the fact that different chemical forms of selenium have different toxic potentials. In the published reports reviewed herein, serum selenium concentrations span the following ranges: 400-30,000 micro g/L associated with acute toxicity, 500-1400 micro g/L associated with chronic toxicity, and 1400 micro g/L. Tissue selenium levels show a complex pattern and significant elevations in organs such as kidney are not always indicative of toxicity. As with many trace elements, measuring selenium concentrations in body fluids and tissues tends to be easier than understanding what the results mean.

Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice.

Abstract: In recent years, a number of investigations on the antidiabetic effects of supranutritional selenate doses have been carried out. Selenate (selenium oxidation state +VI) was shown to possess regulatory effects on glycolysis, gluconeogenesis and fatty acid metabolism, metabolic pathways which are disturbed in diabetic disorders. An enhanced phosphorylation of single components of the insulin signalling pathway could be shown to be one molecular mechanism responsible for the insulinomimetic properties of selenate. In type II diabetic animals, a reduction of insulin resistance could be shown as an outcome of selenate treatment. The present study with db/db mice was performed to investigate the antidiabetic mechanisms of selenate in type II diabetic animals. Twenty-one young adult female db/db mice were randomly assigned to three experimental groups (selenium deficient=0Se, selenite-treated group=SeIV and selenate-treated group=SeVI) with seven animals each. Mice of all groups were fed a selenium-deficient diet for 8 weeks. The animals of the groups SeIV and SeVI were supplemented with increasing amounts of sodium selenite or sodium selenate up to 35% of the LD50 in week 8 in addition to the diet by tube feeding. Selenate treatment reduced insulin resistance significantly and reduced the activity of liver cytosolic protein tyrosine phosphatases (PTPs) as negative regulators of insulin signalling by about 50%. In an in vitro inhibition test selenate (oxidation state +VI) per se did not inhibit PTP activity. In this test, however, selenium compounds of the oxidation state +IV were found to be the actual inhibitors of PTP activity. Selenate administration in vivo further led to characteristic changes in the selenium-dependent redox system, which could be mimicked in an in vitro assay and provided further evidence for the intermediary formation of SeIV metabolites. The expression of peroxisome proliferator-activated receptor gamma (PPARgamma), another important factor in the context of insulin resistance and lipid metabolism, was significantly increased by selenate application. In particular, liver gluconeogenesis and lipid metabolism were influenced strongly by selenate treatment. In conclusion, our results showed that supranutritional selenate doses influenced two important mechanisms involved in insulin-resistant diabetes, namely, PTPs and PPARgamma, which, in turn, can be assumed as being responsible for the changes in intermediary metabolism, e.g., gluconeogenesis and lipid metabolism. The initiation of these mechanisms thereby seems to be coupled to the intermediary formation of the selenium oxidation state +IV (selenite state) from selenate.

Selenium yeast: Composition, quality, analysis, and safety

Abstract: Selenium yeast, produced by growing select strains of Saccharomyces cerevisiae in Se-rich media, is a recognized source of organic food-form Se, but the determination of its exact composition with respect to the Se species present produced conflicting results. Improved methods of analysis have since revealed it to contain 90+ % of its Se in the form of selenomethionine, the principal organic nutritional form of Se for higher animals and hu- mans. The safety record of Se yeast is excellent: During the three decades of its world-wide use as a source of supplemental Se, no cases of Se poisoning have occurred due to dosage or formulation errors.

Sorption of selenite ions on hematite

Abstract: The sorption of selenite from aqueous solutions onto hematite was investigated as a function of pH (2–12), ionic strength (0.01–0.1 M), and concentration of selenium ( 10 −7 – 10 −2 M ). The sorption may proceed according to two processes: surface complexation, followed by the precipitation of ferric selenite starting at approximate [ Se ] = 4 × 10 −4 M (surface coverage > ca. 2 at nm−2). The sorption isotherms have been fitted by a Tempkin equation. A surface complexation model (2-pK/Constant Capacitance Model) was used to fit the sorption data. The nature of the surface species of selenite cannot be determined by modeling since monodentate >FeO Se(O)O− or >FeO Se(O)OH and bidentate (>FeO)2SeO surface complexes are both able to fit the experimental data. The reversibility and kinetics of sorption were also studied. The affinity of selenite ions toward hematite, expressed as the distribution coefficient with respect to the surface area ( K D in L m−2), was compared with results published for other ferric oxides (goethite and amorphous ferric oxide). It was found that the reactivity toward selenite is similar, contrary to acid–base properties which depend on the nature of the oxide and its level of purity.

Selenium species bioaccessibility in enriched radish (Raphanus sativus): a potential dietary source of selenium.

Abstract: An in vitro gastrointestinal method was employed to predict the potential bioavailability of selenium and its species from radish, belonging to the Brassicaceae family, grown in hydroponics media in the presence of inorganic selenium, such as Na2SeO3 and Na2SeO4. A low transformation of Se into organic forms was observed in radish plants grown in Se(VI)-enriched culture media. On the contrary, in those plants exposed to selenite, >95% of the total selenium was found as selenocystine (SeCys2), selenomethionine (SeMet), and Se-methylselenocysteine (SeMetSeCys). The concentrations of these species in fresh samples remained almost unaltered after a simulated gastrointestinal digestion. Therefore, a high selenium content of Se-methylselenocysteine (65%), previously reported as a cancer chemopreventive species, remained in the potentially bioabsorbable fraction. As these plants usually undergo a short development cycle, these results suggest that radish enriched in selenite could be a good choice as an organoselenium supplement for the human diet and animal feed.

Cancer Chemoprevention by Garlic and Garlic-Containing Sulfur and Selenium Compounds

Abstract: As early as 1550 B.C., Egyptians realized the benefits of garlic as a remedy for a variety of diseases. Many epidemiological studies support the protective role of garlic and related allium foods against the development of certain human cancers. Natural garlic and garlic cultivated with selenium fertilization have been shown in laboratory animals to have protective roles in cancer prevention. Certain organoselenium compounds and their sulfur analogs have been identified in plants. Organoselenium compounds synthesized in our laboratory were compared with their sulfur analogs for chemopreventive efficacy. Diallyl selenide was at least 300-fold more effective than diallyl sulfide in protecting against 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas in rats. In addition, benzyl selenocyanate inhibited the development of DMBA-induced mammary adenocarcinomas and azoxymethane-induced colon cancer in rats and benzo[a]pyrene-induced forestomach tumors in mice. The sulfur analog, benzyl thiocyanate, had no effect under the same experimental conditions. Furthermore, we showed that 1,4-phenylenebis(methylene)selenocyanate, but not its sulfur analog, significantly inhibited DMBA-DNA adduct formation and suppressed DMBA-induced mammary carcinogenesis. Collectively, these results indicate that structurally distinctive organoselenium compounds are superior to their corresponding sulfur analogs in cancer chemoprevention. Additionally, synthetic aromatic selenocyanates are more effective cancer chemopreventive agents than the naturally occurring selenoamino acids. Because plants are capable of utilizing selenium in a manner similar to that in sulfur assimilation pathways, future studies should aim at determining whether, under appropriate conditions, these potent cancer chemopreventive synthetic selenium compounds can be synthesized by garlic and related allium foods.

Selenium, iron, copper, and zinc levels and copper-to-zinc ratios in serum of patients at different stages of viral hepatic diseases.

Abstract: Viral hepatic diseases, especially those induced by the hepatitis B virus, can progress into more serious pathological outcomes and eventually to hepatocellular carcinoma. A growing body of evidence indicates that many trace elements play important roles in a number of carcinogenic processes that proceed through various mechanisms. To examine the status of trace elements during the development of hepatic carcinoma, we determined the selenium, iron, copper, and zinc levels and copper-to-zinc ratios in the serum of patients at different stages of viral hepatic disease. We observed significant changes in the selenium, iron, copper, and zinc levels in the serum of patients having hepatocellular carcinoma, relative to those of healthy controls (p < 0.05). The mean serum copper level in patients with hepatocellular carcinoma was significantly higher than that of the control group. In contrast, the mean selenium, iron, and zinc levels in patients having hepatocellular carcinoma were significantly lower than those of the control group. In addition, the mean zinc level in the serum of patients with hepatic cirrhosis was significantly lower than that of the control group (p < 0.05). Moreover, we found markedly elevated Cu: Zn ratios (p < 0.05) in patients having hepatic cirrhosis or hepatocellular carcinoma. Our findings imply that the levels of some trace elements, such as selenium, iron, copper, and zinc, and Cu: Zn ratios, might serve as biomarkers for the increased severity of viral hepatic damage.

The central role of metal coordination in selenium antioxidant activity.

Abstract: Oxidative DNA damage occurs in vivo by hydroxyl radical generated in metal-mediated Fenton-type reactions. Cell death and mutation caused by this DNA damage are implicated in neurodegenerative and cardiovascular diseases, cancer, and aging. Treating these conditions with antioxidants, including highly potent selenium antioxidants, is of growing interest. Gel electrophoresis was used to directly quantify DNA damage inhibition by selenium compounds with copper and H2O2. Selenocystine inhibited all DNA damage at low micromolar concentrations, whereas selenomethionine showed similar inhibition at 40 times these concentrations, and 2-aminophenyl diselenide showed no effect. DNA damage inhibition by these selenium compounds does not correspond to their glutathione peroxidase activities, and UV−vis and gel electrophoresis results indicate that selenium−copper coordination is essential for DNA damage inhibition. Understanding this novel metal-coordination mechanism for selenium antioxidant activity will aid in th...

Comparative toxicosis of sodium selenite and selenomethionine in lambs.

Abstract: Excess consumption of selenium (Se) accumulator plants can result in selenium intoxication. The objective of the study reported here was to compare the acute toxicosis caused by organic selenium (selenomethionine) found in plants with that caused by the supplemental, inorganic form of selenium (sodium selenite). Lambs were orally administered a single dose of selenium as either sodium selenite or selenomethionine and were monitored for 7 days, after which they were euthanized and necropsied. Twelve randomly assigned treatment groups consisted of animals given 0, 1, 2, 3, or 4 mg of Se/kg of body weight as sodium selenite, or 0, 1, 2, 3, 4, 6, or 8 mg of Se/kg as selenomethionine. Sodium selenite at dosages of 2, 3, and 4 mg/kg, as well as selenomethionine at dosages of 4, 6, and 8 mg/kg resulted in tachypnea and/or respiratory distress following minimal exercise. Severity and time to recovery varied, and were dose dependent. Major histopathologic findings in animals of the high-dose groups included multifocal myocardial necrosis and pulmonary alveolar vasculitis with pulmonary edema and hemorrhage. Analysis of liver, kidney cortex, heart, blood, and serum revealed linear, dose-dependent increases in selenium concentration. However, tissue selenium concentration in selenomethionine-treated lambs were significantly greater than that in lambs treated with equivalent doses of sodium selenite. To estimate the oxidative effects of these selenium compounds in vivo, liver vitamin E concentration also was measured. Sodium selenite, but not selenomethionine administration resulted in decreased liver vitamin E concentration. Results of this study indicate that the chemical form of the ingested Se must be known to adequately interpret tissue, blood, and serum Se concentrations.

Selenium Biochemistry: Mammalian Selenoenzymes

Abstract: Within the past ten years selenium biochemistry has attracted an increasing number of investigators interested both in the beneficial and the toxic effects of the element in biological systems. In 1957 two independent research groups showed that the trace element selenium is an important nutrient for animals. Klaus Schwartz at the National Institutes of Health in Bethesda isolated a selenium-containing factor that prevented rats fed a Torula yeast based diet from developing liver necrosis. 1 Investigators at the Lederle Laboratories in Pearl River, NY, found that exudative diathesis in poultry was prevented by addition of selenium to the diet. 2 Predating these discoveries by three years was a report 3 that Escherichia coli required selenium and molybdenum for synthesis of active formate dehydrogenase, but this finding attracted little attention at a time when the revelance of discoveries made in bacterial physiology to mammalian physiology was not widely appreciated. A possible biochemical explanation of the beneficial effects of selenium in animals came several years later when the trace element was discovered to be an essential component of an important antioxidant enzyme, glutathione peroxidase. 4,5 At the same time a low molecular weight component, protein A, of the Clostridial glycine reductase complex was shown to be a selenoprotein 6 and the selenium-containing moiety was identified as selenocysteine. 7 The techniques developed for alkylation of the reduced selenocysteine and identification of the carboxymethyl and carboxyethyl derivatives of the selenoamino acid in acid hydrolysates of Clostridial selenoprotein A facilitated identification of selenocysteine in glutathione peroxidase and, later, in other selenoproteins. 8

Uptake and speciation of selenium in garlic cultivated in soil amended with symbiotic fungi (mycorrhiza) and selenate.

Abstract: The scope of the work was to investigate the influence of selenate fertilisation and the addition of symbiotic fungi (mycorrhiza) to soil on selenium and selenium species concentrations in garlic. The selenium species were extracted from garlic cultivated in experimental plots by proteolytic enzymes, which ensured liberation of selenium species contained in peptides or proteins. Separate extractions using an aqueous solution of enzyme-deactivating hydroxylamine hydrochloride counteracted the possible degradation of labile selenium species by enzymes (such as alliinase) that occur naturally in garlic. The selenium content in garlic, which was analysed by ICP-MS, showed that addition of mycorrhiza to the natural soil increased the selenium uptake by garlic tenfold to 15 microg g(-1) (dry mass). Fertilisation with selenate and addition of mycorrhiza strongly increased the selenium content in garlic to around one part per thousand. The parallel analysis of the sample extracts by cation exchange and reversed-phase HPLC with ICP-MS detection showed that gamma-glutamyl-Se-methyl-selenocysteine amounted to 2/3, whereas methylselenocysteine, selenomethionine and selenate each amounted to a few percent of the total chromatographed selenium in all garlic samples. Se-allyl-selenocysteine and Se-propyl-selenocysteine, which are selenium analogues of biologically active sulfur-containing amino acids known to occur in garlic, were searched for but not detected in any of the extracts. The amendment of soil by mycorrhiza and/or by selenate increased the content of selenium but not the distribution of detected selenium species in garlic. Finally, the use of two-dimensional HPLC (size exclusion followed by reversed-phase) allowed the structural characterisation of gamma-glutamyl-Se-methyl-selenocysteine and gamma-glutamyl-Se-methyl-selenomethionine in isolated chromatographic fractions by quadrupole time-of-flight mass spectrometry.

Effects of dietary supplements of selenium, vitamin E or combinations of the two on antibody responses of broilers

Abstract: 1. The effects of selenium and vitamin E supplementation on some immune parameters were investigated in broilers. 2. Broiler chicks were fed on maize-soybean diets with different concentrations of vitamin E (0-200 mg/kg) and selenium (0-0.2 mg/kg diet) either alone or in combinations from 1 to 42 d of age. 3. Chicks were immunised against Newcastle disease virus (NDV) vaccine at 21 d of age and haemagglutination inhibition (HI) titres were determined after 10 d. 4. Chicks receiving supplements of 200 mg vitamin E/kg and 0.2 mg selenium/kg produced significantly higher HI antibody titres. This was associated with an increased serum concentration of total immunoglobulins and circulatory immune complexes. 5. The chicks given 200 mg vitamin E/kg and 0.2 mg selenium/kg had significantly heavier spleen and bursa. 6. These results suggested that vitamin E and selenium have synergistic effects on immune responses.

Selenium and antioxidant defenses as major mediators in the development of chronic heart failure

Abstract: Increased oxidative stress is involved in the pathogenesis of chronic heart failure (CHF), the common end result of most cardiac diseases. Selenium is an "essential" trace element, which means that it must be supplied by our daily diet and that its blood and tissue concentrations are extremely low. Selenium has a variety of functions. It is a key component of several functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase (GPx) enzymes, which remove hydrogen peroxide and the harmful lipid hydroperoxides generated in vivo by oxygen-derived species. GPx deficiency exacerbates endothelial dysfunction, a major contributing factor in the severity of CHF symptoms, in various conditions such as hyperhomocysteinemia. This suggests that homocysteine may be involved in the CHF associated endothelial dysfunction through a peroxide-dependent oxidative mechanism. Selenium also plays a role in the control of thyroid hormone metabolism and in protection against organic and inorganic mercury. One possible additional mechanism by which low selenium may compromise cardiovascular condition may be through the effect of selenium on the synthesis and activity of deiodinases, enzymes converting thyroxin into the biologically active triiodothyronine. Selenium and iodine actually interact in cardiovascular physiology, and further studies are needed to examine their role, in isolation and in association, in the development of CHF. Thus, selenium (through its role in selenoenzymes, thyroid hormones, and interactions with homocysteine and endothelial function) appears to be a major mediator in several pathways potentially contributing to CHF development.

Altered hippocampus synaptic function in selenoprotein P deficient mice.

Abstract: Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS.