Showing papers on "Selenium published in 1991"

Chemical form of selenium, critical metabolites, and cancer prevention.

Abstract: Methylated selenides are prominent metabolites at the dietary levels used for obtaining anticarcinogenic effects with selenium. The present study reports the chemopreventive activities of 2 novel selenium compounds, Se-methylselenocysteine and dimethyl selenoxide, in the rat dimethylbenz(a)anthracene-induced mammary tumor model. Other treatment groups were supplemented with either selenite or selenocystine for comparative purposes. Each selenium compound was tested at different levels and was given to the animal starting 1 week before dimethylbenz(a)anthracene administration and continued until sacrifice. Results of the carcinogenesis experiments showed that the relative efficacy with the four compounds was Se-methylselenocysteine greater than selenite greater than selenocystine greater than dimethyl selenoxide. In correlating the chemical form and metabolism of these selenium compounds with their anticarcinogenic activity, it is concluded that: (a) selenium compounds that are able to generate a steady stream of methylated metabolites, particularly the monomethylated species, are likely to have good chemopreventive potential; (b) anticarcinogenic activity is lower for selenoamino acids, such as selenocysteine following conversion from selenocystine, which have an escape mechanism via random, nonstoichiometric incorporation into proteins; and (c) forms of selenium, as exemplified by dimethyl selenoxide, which are metabolized rapidly and quantitatively to dimethyl selenide and trimethylselenonium and excreted, are likely to be poor choices. We also undertook a separate bioavailability study using Se-methylselenocysteine, dimethyl selenoxide, and trimethylselenonium as the starting compounds for delivering selenium with one, two, or three methyl groups, and measured the ability of these compounds to restore glutathione peroxidase activity in selenium-depleted animals. All three compounds were able to fully replete this enzyme, although with a wide range of efficiency (Se-methylselenocysteine greater than dimethyl selenoxide greater than trimethylselenonium), suggesting that complete demethylation to inorganic selenium is a normal process of selenium metabolism. However, the degree to which this occurs under chemoprevention conditions would argue against the involvement of selenoproteins in the anticarcinogenic action of these selenium compounds.

Contaminants in Drainage Water and Avian Risk Thresholds

Abstract: The toxicity of selenium to avian embryos is one of the most restrictive constraints on options for managing agricultural drainage water. Although selenium in eggs strongly predicts embryotoxicity, waterborne selenium (on a total recoverable basis) often is an unreliable predictor of average realized selenium in eggs. For the San Joaquin Valley, however, the algebraically derived equation Log (Mean Egg Se) = 3.66 + 0.57 Log (Waterborne Se) is a good predictor of the maximum potential for selenium bioaccumulation in avian eggs. Using eared grebes (Podiceps nigricollis) as an indicator species for bioaccumulation potential, the average absolute difference between observed and predicted mean selenium in eggs was only 6 percent for test cases at waterborne concentrations of 2.8, 15, 126, 176 p/b (total recoverable) selenium. Various estimates of biologically important thresholds indicate that it would be prudent to consider drainage water with 3 to 20 p/b selenium as peripherally hazardous to aquatic birds (i.e., hazardous to some species under some environmental conditions) and drainage water with more than 20 p/b selenium as widely hazardous to aquatic birds (i.e., hazardous to most species under most environmental conditions). To prevent most avian toxicity, a reasonable goal for chemical or biological decontamination technologies would be concentrations of waterborne selenium < 10 p/b. Likewise, to minimize avian contamination, a reasonable goal of purity would be waterborne selenium < 2.3 p/b. When these water standards are technically or financially unattainable, actions to significantly reduce avian use of contaminated drainage water are necessary.

Molecular biology of selenium with implications for its metabolism.

Abstract: Selenium has a highly specific metabolism centered around its incorporation as selenocysteine into selenoproteins. An outline of this metabolism has emerged from recent molecular biological and biochemical studies of bacteria and animals. A unique tRNA, designated tRNA[Ser]Sec, is charged with L-serine, which is then converted through at least two steps to selenocysteine. With the aid of a unique translation factor, the selenocysteinyl-tRNA[Ser]Sec recognizes specific UGA codons in mRNA to insert selenocysteine into the primary structure of selenoproteins. Turnover of selenoproteins presumably liberates selenocysteine which is toxic in its free form. Selenocysteine beta-lyase catabolizes free selenocysteine and makes its selenium available for reuse. Proteins contain almost all the selenium in animals. Of the known selenoproteins, the glutathione peroxidases contain the most selenium. Cellular and plasma glutathione peroxidases are products of different genes but have 44% identity of amino acid sequence. ...

Physiological and nutritional importance of selenium.

Abstract: The essential trace element selenium has recently attracted attention because of its potentialities in the maintenance of human health. Selenium forms part of the active site of the peroxide-destroying enzyme glutathione peroxidase, and it also has other functions, for example in biotransformation, detoxification and the immune response. Functional and clinical consequences of selenium deficiency states have been described, and the selenium requirement, which is influenced by the usual selenium exposure, has been discussed. Wide variations have been found in selenium status in different parts of the world, and populations or groups of patients exposed to marginal deficiency are more numerous than was previously thought. Current research activities in the field of human medicine and nutrition are devoted to the possibilities of using selenium for the prevention or treatment of degenerative or free radical diseases such as neurological disorders, inflammatory diseases or cancer. Pharmacological selenium doses are also recommended as an adjuvant in some treatments.

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.

Abstract: Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism.

Total diet study nutritional elements, 1982-1989.

Abstract: Daily intakes of sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, selenium, iodine, copper, and manganese for eight age-sex groups are presented for 1982 to 1989. Compared with the intakes recommended by the National Academy of Sciences, sodium intakes (which did not include discretionary salt) exceeded the estimated minimum requirement; intakes of potassium, phosphorus, selenium, and iodine were adequate for all groups; and copper intakes were low (less than 80% of the suggested intake) for all groups. In addition, calcium, magnesium, iron, and manganese were low in the diets of teenage girls; calcium, magnesium, and iron were low in the diets of adult women; calcium, magnesium, and zinc were low in the diets of older women; calcium and zinc were low in the diets of 2-year-olds; and magnesium was low in the diets of teenage boys and older men. The primary food group source for each element was dairy products for potassium, calcium, phosphorus, magnesium, and iodine; grain products for sodium, iron, and manganese; and animal flesh for zinc, selenium, and copper.

Methods in determination of selenium states.

Abstract: Selenium status in man has been assessed either by determination of the selenium concentration in biological materials or by the measurement of biochemical or clinical selenium-dependent functions. Over and above the discussion of normal levels and of the numerous factors liable to influence the above mentioned indices, the present review more specifically deals with the sensitivity of various parameters to changing selenium status, both in deficiency states and in over-exposure to the element, and the attempt is made to establish the specificity of these indicators in the diagnosis of selenium states. The possibilities for defining "adequate" or "optimum" selenium concentrations are also examined.

Selenium and the Immune Response

Abstract: Selenium has a long history as a toxicant: the writings of Marco Polo suggest that merchants who ventured into Western China in the late 13th century to buy rhubarb lost their beasts of burden because seleniferous grasses were used as forage (see Rosenfeld & Beath, 1964). The element acquired a new reputation from 1957, however, when it was established as an essential micronutrient (Schwarz & Foltz, 1957) and later as an integral component of glutathione peroxidase (EC 1.11.1.9; GSHPx) (Rotruck et al. 1973). GSHPx, in alliance with vitamin E, forms part of the cell’s defence against reactive metabolites of oxygen which are produced during the normal operation of a wide spectrum of biological processes; damage to cell membranes and the cytoskeleton will occur if these metabolites are not kept under control (see Nhve, 1989). In Se-deficient animals there is a reduction in GSHPx activity accompanied by a variety of cellular malfunctions, including a loss of immunocompetence (for review, see KiremidjianSchumacher & Stotzky, 1987). The present work will examine the extent and severity of this impairment in single Se v. combined Se-vitamin E deficiencies, and develop the idea that measurement of GSHPx activity provides, at best, an incomplete guide to immunological status. Given that Se has an essential biological role and that local food sources provide very small amounts of it to humans and particularly to livestock in several parts of the world (Gissel-Nielsen et al. 1984), supplementation has become commonplace. Unfortunately, new examples of Se poisoning have emerged, through maladministration of supplements on farms and commercial piggeries. Although these have sometimes arisen from straightforward mistakes in dietary formulation or mixing (e.g. Hill et al. 1985; Hopper et al. 1985), the temptation to oversupplement has been increased by claims in the literature that doses of Se given to laboratory animals in excess of those required for normal growth and development are particularly effective in promoting immune responses and inhibiting cancers. Such claims need to be judged for different species, stages and antigens, and against the low safety margins reported for Se: maximum concentrations tolerated in the animal diet are said to be about twenty to thirty times greater than levels which meet minimum requirements (0.1 pg/g dry matter (DM); Gissel-Nielsen et al. 1984). The recent poisoning of wildlife on a Californian sanctuary due to an influx of Se-laden water from irrigated farmland (Moore, 1989) has fuelled the debate about acceptable levels of the element.

Determination of dissolved selenium species in environmental water samples using isotope dilution mass spectrometry

Abstract: In order to clarify the species composition of selenium in environmental water samples, analytical methods have been developed for the selective determination of different chemical forms of this element (selenite, selenate, and organic species including trimethylselenonium) using isotope dilution mass spectrometry (IDMS). The species analysis was made possible by means of chromatographic separation procedures and an 82Se-enriched selenate, selenite, and trimethylselenonium spike for the isotope dilution process. The total selenium concentration was determined after decomposition of organic compounds with a HNO3/HCIO4 mixture. Selenium was measured in the mass spectrometer by producing negative Se- thermal ions for detection. Precise determination at the parts-per-trillion level was achieved. This new methodology was applied to different types of natural water samples (groundwater, pond water, river water, moorland lake water) with total selenium concentrations in the range of 200 pg/g to 15 ng/g. Selenite and selenate have been the only detected species in most of the investigated samples, with selenate dominating all except one. In samples with high contents of dissolved organic carbon, however, different organoselenium compounds including trimethylselenonium ions were additionally quantified in the range of 10-95 pg/g. In these cases, the sum of all selenium species agreed well with the independently determined total element concentration.

Response of rat selenoprotein P to selenium administration and fate of its selenium

Abstract: Selenoprotein P is a glycoprotein that contains greater than 60% of the selenium in rat plasma. Physiological experiments were undertaken to gain insight into selenoprotein P function. Selenium-deficient rats were injected with doses of selenium ranging from 25 to 200 micrograms/kg, and the appearance of selenoprotein P was compared with the appearance of glutathione peroxidase activity in plasma and in liver. Selenoprotein P concentration increased to 35% of control by 6 h, whereas glutathione peroxidase activity increased minimally or not at all. Moreover, in rats given 100 and 200 micrograms selenium/kg, selenoprotein P reached 75% of its concentration in control rats at 24 h, whereas glutathione peroxidase activity reached only 6% of control. Cycloheximide pretreatment blocked the appearance of selenoprotein P in response to selenium injection. Male and female rats had similar concentrations of selenoprotein P. Partially purified selenoprotein P and plasma glutathione peroxidase labeled with 75Se were administered intravenously to selenium-deficient and control rats. 75Se given as selenoprotein P disappeared more rapidly from plasma than did 75Se given as glutathione peroxidase. Selenium deficiency did not significantly affect 75Se disappearance from plasma. At 2 h, brain, but not other tissues, took up more 75Se in selenium-deficient rats than in control rats when 75Se was given as selenoprotein P. This suggests that brain has a specific uptake mechanism for selenium given in the form of selenoprotein P. These results demonstrate that several physiological properties distinguish selenoprotein P from glutathione peroxidase. However, they do not clearly indicate its function.

Effects of Chemical Form and Dosage on the Incorporation of Selenium into Tissue Proteins in Rats

Abstract: We investigated the incorporation of Se into the proteins of liver and muscle, the two main Se pools, during replenishment of Se-deficient rats with normal or large doses of 75Se-labeled selenite and selenomethionine, doses equivalent to the amounts ingested from a diet with 02 or 2 mg Se/kg With the higher intake, Se levels were elevated More Se was retained from selenomethionine than from selenite After separation of the labeled proteins, it was apparent that the higher tissue Se contents were mainly due to nonspecific incorporation into a large number of proteins We observed no differences between the two chemical forms with regard to the formation of the specific selenoproteins The 10-fold increase in the Se supply led to a relatively small rise in the levels of these compounds The results indicate that after ingestion of normal amounts of selenite nearly all of the element is present in the specific selenoproteins With increasing doses a part is also incorporated nonspecifically into numerous other proteins In the case of selenomethionine, a part of the element follows the same metabolic pathways, but a percentage is also deposited directly and nonspecifically into proteins in place of methionine

Selenium induces changes in the selenocysteine tRNA[Ser]Sec population in mammalian cells.

Abstract: Two isoacceptors of selenocysteine tRNA[Ser]Sec are present in higher vertebrates which are responsible for donating selenocysteine to protein. One such selenocysteine containing protein, glutathione peroxidase, requires selenium for its translation and transcription. Since tRNA[Ser]Sec is a critical component of the glutathione peroxidase translational machinery, the levels and distributions of its isoacceptors were examined from both human and rat cells grown in chemically defined media with and without selenium. Not only did the level of the selenocysteine tRNA[Ser]Sec population increase approximately 20% in cells grown in the presence of selenium, but the distributions of the two isoacceptors also changed relative to each other.

The role of selenium in thyroid hormone metabolism.

Abstract: In animals, decreases in selenium-containing glutathione peroxidase activity and the resultant impairment of peroxide metabolism can account for many, but not all of the biochemical and clinical ch...

Pharmacology of synthetic organic selenium compounds

Abstract: The similarity in the chemical properties of sulfur and selenium has tempted medical chemists for many years to prepare, for comparative purposes, a wide variety of selenium derivatives of sulphur- or oxygen-containing compounds. Because of the widespread use of this chemical comparison, the list of published and/or patented structures of organic selenium compounds is extensive. Two detailed, but rather uncritical, reviews of organic selenium compounds synthesized as possible drugs have been written in the past, by Klayman in 1973 [1] and by Shamberger in 1983 [2]. Many of the compounds reviewed were synthesized, however, as part of a chemical series and were never studied for biological activity beyond initial screening. Other compounds had similar activities to the parent sulfur- or oxygen-containing analogues and therefore offered no pharmacological advantage. With the discovery of the essential role of selenium in the active center of the enzyme glutathione peroxidase [3] and the increasing understanding of the physiological importance of selenium in the regulation of oxidative damage [4,5], interest has grown in the synthesis of organic compounds on the basis of the biological and chemical properties of their selenium moieties rather than as analogues of known compounds.

In situ bacterial selenate reduction in the agricultural drainage systems of western Nevada

Abstract: Dissimilatory in situ selenate reduction to elemental selenium in sediments from irrigated agricultural drainage regions of western Nevada was measured at ambient Se oxyanion concentrations. Selenate reduction was rapid, with turnover rate constants ranging from 0.04 to 1.8 h-1 at total Se concentrations in pore water of 13 to 455 nM. Estimates of removal rates of selenium oxyanions were 14.38, and 155 mumol m-2 day-1 for South Lead Lake, Massie Slough, and Hunter Drain, respectively.

Uptake of selenium by freshwater phytoplankton

Abstract: The uptake of three forms of Se, selenate, selenite and selenomethionine, was examined in three species of freshwater algae, Anabaena flos-aquae (Cyanophyceae), Chlamydomonas reinhardtii (Chlorophyceae), and Cyclotella meneghiania (Bacillariophyceae) in a defined medium using radiotracers at Se concentrations representative of contaminated systems. Based on the relative accumulation by live vs. heat-killed cells, and linear accumulation through time, selenate accumulation by all three species appears to be a physiological process. However, selenite accumulation at these concentrations appears to be due largely to sorption rather than active uptake, as shown by rapid initial accumulation and the fact that accumulation by heat-killed cells was nearly equal to that of dead cells. Both selenate and selenite uptake rates increased linearly with concentration over the range of 1 to 50 µg L−1. Selenomethionine uptake is a biological process with saturable uptake kinetics (Ks ranging from about 2 to 30 µg L−1 Se), with much greater uptake rates than the other two forms, and little inactive sorbtion to heat-killed cells.

Comparative Antioxidant Effectiveness of Dietary β-Carotene, Vitamin E, Selenium and Coenzyme Q10 in Rat Erythrocytes and Plasma

Abstract: Five groups of five weanling rats were each fed a Torula yeast-based diet either unsupplemented or supplemented with 30 mg beta-carotene/kg, 30 IU vitamin E/kg, 1 mg selenium/kg or 30 mg coenzyme Q10/kg. Elevated levels of plasma aspartate aminotransferase and alanine aminotransferase are sensitive indicators of liver damage. The former enzyme was lower (P less than 0.01) in the vitamin E-, selenium- and beta-carotene-supplemented groups than in the unsupplemented control group, and the latter enzyme was lower in the vitamin E- and selenium-supplemented groups, suggesting a relatively equal effectiveness of these three antioxidants against liver damage. Erythrocytes were tested for protection against uninduced oxidative damage or that induced by 1 mmol/L bromotrichloromethane (BrCl3C) by measuring thiobarbituric acid-reactive substances (TBARS), hemoglobin, hemolysis, protein precipitation, alanine release and several enzyme activities. In untreated erythrocytes, selenium, beta-carotene and coenzyme Q10 exhibited protection by lowering (P less than 0.05) TBARS and alanine release, but only vitamin E protected against hemolysis. In BrCl3C-treated erythrocytes, vitamin E, selenium and beta-carotene protected by decreasing (P less than 0.05) protein precipitation, whereas selenium and beta-carotene decreased alanine release. The results of this study suggested that, in a manner analogous to vitamin E and selenium, beta-carotene and coenzyme Q10 function as antioxygenic nutrients.