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Selenium in ruminant nutrition: a review.

The early interest in selenium related primarily to its toxicity, but since 1957 the element has been recognized as a dietary essential. The dietary requirement for selenium by most species is about .1 ppm. Deficiencies of selenium in cattle and sheep have been confirmed under natural grazing conditions in many countries of the world. Overt signs of inadequacy such as white muscle disease (nutritional muscular dystrophy) occur primarily in young calves or lambs born to selenium deficient dams. Infertility has increased in ewes grazing pastures low in selenium. In general, signs of deficiency have not occurred in older animals such as finishing beef cattle and lactating dairy cows. Subclinical deficiencies of selenium are not determined easily, however, and thus an inadequacy of the element may be limiting maximum animal performance under certain circumstances of drylot feeding. The current nutritional status of ruminant animals in many geographical areas and involving various feeding programs with this element has not been established. The recent widespread deficiency problems with nonruminants suggest that such an assessment should be made. Concentration of selenium in tissue, particularly in the liver, has been used in establishing selenium status of the animal. With lambs glutathione peroxidase activity in certain tissues may be a more accurate indicator of selenium adequacy than is selenium content of the tissue. Supplemental sodium selenite and sodium selenate by either oral administration or parenteral injection have prevented clinical signs of selenium deficiency and animal losses in both ruminant and nonruminant animals. Heavy pellets containing elemental selenium for placement in the rumen have proved effective. In general, organic forms of selenium are absorbed more readily by animals than are inorganic compounds. The dietary requirements for selenium and its metabolism are influenced by many nutrient interrelationships, including its interactions with sulfur, lipids, vitamin E, proteins, amino acids, and several microelements. The Food and Drug Administration gave approval in 1974 for the oral administration of supplemental selenium as either sodium selenite or sodium selenate to certain classes of swine and poultry. Similar approval in the United States for ruminants will require additional information, particularly with regard to the influence of dietary intake on concentrations of selenium in tissue and milk in beef and dairy animals.

Animal Feed↗

Nonimmunological host defenses: a review.

Nonimmunological defenses are very diverse in type. Some are directed against already transformed cells and belong to mechanisms of containment. Others exert a surveillance by preventing or inhibiting initial events of carcinogenesis. Chalones and oncolytic factors in sera and exudates are agents of containment. Under appropriate circumstances, the autoxidation of thiols and the formation of mixed disulfides lead to destruction of tumor cells in vitro and in vivo. Both processes involve the generation of superoxide radicals and of hydrogen peroxide which, in turn, activate the peroxide:peroxidase:halide system. Thiol:disulfide ratios and interchange codetermine the antioxidative activity of cellular membranes, thus bearing on carcinogenesis. Many aliphatic and aromatic antioxidants are endowed with anticarcinogenic properties. The fact that they are inhibitors of free radical processes corroborates the increasingly evident role of free radicals in carcinogenesis. Endogenous antioxidants and exogenous ones in foods are agents of surveillance. Antioxidant activity, linked with the ergastoplasm, points to a homeostatic mechanism that prevents self-accelerating chain reactions from leading to membrane damage or to carcinogenesis. Carcinogens can also be inactiviated by microsomal enzymes belonging to an overall mechanism of detoxification. Activity levels of these systems depend on diet and state of nutrition. They may be naturally very low, but they can be increased with various inducers.

Animals↗

Resveratrol reduces oxidative stress induced by platinum compounds in blood platelets.

The effects of resveratrol (trans-3,4',5-trihydroxystilbene) on the oxidative stress in blood platelets induced by platinum compounds [cisplatin and selenium-cisplatin conjugate] were studied in vitro. The production of thiobarbituric acid reactive substances (TBARS), the level of conjugate diene, the generation of superoxide anion radicals (O2-*) and other reactive oxygen species (O2-*, H2O2, singlet oxygen and organic radicals) were measured by chemiluminescence in blood platelets treated with platinum compounds. Cisplatin at the concentration of 10 microg/ml, as well as selenium-cisplatin conjugate (10 microg/ml) induced oxidative stress in blood platelets: an increase in TBARS, conjugate diene, chemiluminescence and generation of O2-*. In the presence of resveratrol (a natural compound with antioxidant activity) at the concentrations of 1-25 microg/ml, the chemiluminescence, the levels of O2-*, conjugate diene and TBARS were reduced (p < 0.05). We showed that resveratrol at different concentrations (1-25 microg/ml) had a protective effect against oxidative stress in platelets caused by platinum compounds (10 microg/ml) and it diminished platelet lipid peroxidation and reactive oxygen species generation induced by platinum compounds.

Animals↗

Synthesis, reactivity and structural studies of selenide bridged carboranyl compounds.

Reaction of the lithium salt Li[1-R-1,2-closo-C(2)B(10)H(10)] with selenium under mild conditions, followed by hydrolysis gave the diselenide compound (1-Se-2-R-1,2-closo-C(2)B(10)H(10))(2) in contrast to the well-reported mercapto compounds 1-SH-2-R-1,2-closo-C(2)B(10)H(10) obtained using a similar synthetic procedure. Details for the preparation and X-ray structural characterisation of the new compounds (2-Me-1,2-closo-C(2)B(10)H(10))(2)Se, (1-Se-2-R-1,2-closo-C(2)B(10)H(10))(2) (R = Me, Ph, ) are specified. To further explore the mechanism of the dimerization reaction, the complex [Au(1-Se-2-Me-1,2-closo-C(2)B(10)H(10))(PPh(3))] was synthesized, confirming the existence of the intermediate Li[1-Se-2-R-1,2-closo-C(2)B(10)H(10)] at the early stages of the reaction before selenium oxidation. Theoretical calculations and cyclic voltammetry (CV) studies were carried out to compare the bonding nature of the sulfur and the selenium analog compounds. It was determined that diselenides have a higher tendency to reduce with respect to the disulfides and all chalcogen atoms were found to be positively charged.

Journal Article↗

The activity of methylated and non-methylated selenium species in lymphoma cell lines and primary tumours.

BACKGROUND: Diffuse large B-cell lymphoma patients with low serum selenium concentration at presentation have a lower response rate and overall survival than patients with higher serum selenium. The co-administration of selenium with conventional chemotherapy may be useful in these patients. PATIENTS AND METHODS: We investigated the activity of two selenium species, methylseleninic acid (MSA) and selenodiglutathione (SDG) in a panel of human lymphoma cell lines and in a primary lymphoma culture system. RESULTS: Both compounds demonstrated cytostatic and cytotoxic activity with EC(50) values in the range 1.0-10.2 microM. Cell death was associated with an increase in the sub-G1 (apoptotic) fraction by flow cytometry and was not preceded by any obvious cell cycle arrest. SDG, but not MSA, resulted in marked increases in intracellular ROS, particularly in CRL2261 and SUD4 cells in which the cytotoxic activity of SDG was partly, or completely, inhibited by n-acetyl cysteine, suggesting a dependence on ROS for activity in some cells. Both MSA and SDG showed a concentration dependent reduction in percentage viability after a 2-day exposure in primary lymphoma cultures, with EC(50) values in the range 39-300 microM and 9-28 microM, respectively. CONCLUSION: The selenium compounds MSA and SDG induce cell death in lymphoma cell lines and primary lymphoma cultures, which with SDG may be partly attributable to the generation of ROS.

Apoptosis↗

Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion.

Compounds with potential antiplatelet activity can be used in the therapy of cardiovascular disorders. We investigated the effects of three different antioxidants with carcinostatic property: trans-resveratrol, Trolox a water-soluble analog of vitamin E, and inorganic selenocompounds (sodium selenite and selenate) on blood platelet adhesion to fibrinogen (Fg). Adhesion, the initial step of platelet activation, was estimated by the colorimetric method with BCA (bicinchoninic acid) solution in 96-well Fg-coated microtiter dishes. It was shown that resveratrol significantly inhibited adhesion of both thrombin- and ADP-activated platelets to Fg. After incubation of platelets for 30 min. at 37 degrees C with resveratrol at the concentration of 100 microg/ml above 40% inhibition of adhesion was achieved. The inhibition of platelet adhesion of Fg caused by Trolox was lower than by resveratrol and at higher concentration (1 mM) reached maximum 12%. We also demonstrated that neither sodium selenite nor selenate significantly altered platelet adhesion to Fg. We conclude that changed adhesion of blood platelets to Fg in the presence of resveratrol and Trolox, but not selenium may be the result of different antioxidative activities of tested compounds.

Animals↗

Effects of starvation on the urinary contents of primary thromboxane and prostacyclin metabolites and a possible selenium-dependent role of prostacyclin in the renal handling of ketone bodies.

The aim of this study was to investigate whether urinary prostanoids, as an index of renal synthesis of these compounds, are affected in selenium (Se) deficiency and, if so, whether such changes could add to our understanding of the high excretion of ketone bodies in Se-deficient rats (p < 0.005 vs Se-adequate rats). Male rats were fed a Se-deficient diet with less than 0.01 mg Se/kg or the same diet supplemented with 0.2 mg Se/kg. The urinary contents of prostaglandin E2 (PGE2), PGF2 alpha and 6-keto PGF1 alpha were not significantly affected by the Se status. However, there was a positive correlation between the urinary contents of ketone bodies and 6-keto PGF1 alpha in Se deficiency (with p < 0.02 for acetaoacetate and p < 0.05 for 3-hydroxybutyrate). In contrast, only negative (nonsignificant) relationships were observed between these same parameters in Se-adequate rats. No correlations between urinary contents of ketone bodies and PGE2, PGF2 alpha or thromboxane B2 (TXB2) were obtained. Compared to fed rats, starvation caused a 4-fold increase in the urinary TXB2 content in Se-adequate, as well as in Se-deficient rats (p < 0.001). Starvation had an opposite effect on the content of 6-keto PGF1 alpha, which decreased (to 64% that of fed animals p < 0.001) in Se-adequate rats and, nonsignificantly (to 93% that of fed animals) in the Se-deficient group. It is concluded that starvation profoundly affects the urinary contents (and thus, probably renal synthesis) of TX and prostacycline (PGI2).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Diphenyl diselenide and ascorbic acid changes deposition of selenium and ascorbic acid in liver and brain of mice.

Sodium selenite (Na2SeO3) is the selenium form used in the composition of dietary supplements, and diphenyl diselenide (PhSe)2 is an important intermediate in organic synthesis, which increases the risk of human exposure to this chemical in the workplace. These compounds have been reported to inhibit the cerebral and hepatic aminolevulinic acid dehydratase (ALA-D) in vitro, and now we show that ascorbic acid can reverse some alterations caused by in vivo selenium exposure, but not ALA-D inhibition. The effect of Na2SeO3 or (PhSe)2 and ascorbic acid on selenium distribution, total non-protein thiol, ascorbic acid content (liver and brain) and haemoglobin was also examined. Mice were exposed to 250 micromol/kg (PhSe)2, or 18.75 micromol/kg Na2SeO3 subcutaneously, and to ascorbic acid, twice a day, 1 mmol/kg intraperitonially, for 10 days. Hepatic ALA-D of mice treated with (PhSe)2 was inhibited about 58% and similar results were observed in the animals that received ascorbic acid supplementation (P<0.01, for (PhSe)2-treated and (PhSe)2+ascorbic acid-treated mice). The haemoglobin content decreased after treatment with (PhSe)2 (P<0.01). However, the haemoglobin content of the (PhSe)2+ascorbic acid group was significantly higher than in the (PhSe)2-treated mice (P<0.05), and similar to control (P>0.10). Ascorbic acid treatment decreased significantly the hepatic and cerebral deposition of Se in (PhSe)2-exposed mice (P<0.01). Hepatic non-protein thiol content was not changed by treatment with (PhSe)2, ascorbic acid or (PhSe)2+ascorbic acid. Hepatic content of ascorbic acid was twice that in mice that received (PhSe)2, independent of ascorbic acid treatment (P<0.001). The results of this study suggest that vitamin C may have a protective role in organodiselenide intoxication.

Animals↗

Diffusibility of selenate, selenite, seleno-methionine, and seleno-cystine during simulated gastrointestinal digestion.

The present study was undertaken to evaluate the in vitro availability of chemically varying forms of selenium (Se), supplemented in cow's milk. Two inorganic (selenite and selenate) and two organic (seleno-methionine [Se-Met] and seleno-cystine [Se-Cys]) Se sources were evaluated. The in vitro availability was estimated by the diffusibility of Se during simulated gastrointestinal digestion. First, the diffusibility was compared after adding a constant amount of Se as either selenate, selenite, seleno-methionine, or Se-Cys in milk samples. Se-Met and selenate were found to be significantly more diffusible than seleno-cystine and selenite under the simulated gastrointestinal conditions. The tendency for superior in vitro availability of selenate and Se-Met compared to selenite and Se-Cys was confirmed for a supplementation range of 5-40 ng/g of Se. This study suggests that the high diffusibility of selenate and Se-Met in a simulated gastrointestinal environment may contribute to their high absorption in vivo.

Animals↗

Excretion of trimethylselenonium ion in human urine.

A method to permit isolation and measurement of trimethylselenonium ion [TMSe, (CH3)3Se+] from 1 liter of human urine was developed. The method was based on precipitation of TMSe with ammonium reineckate, preseparation with anion-exchange resin, and final thermal decomposition and collection of the product in HNO3. It was tested for recovery and separation from other selenium moieties present in urine using both in vivo-labeled rat urine and human urine spiked with unlabeled TMSe. Recoveries from the former were in the range 76.8-87.0% (mean +/- SD: 81.8 +/- 3.7%, n = 5), while for the latter they were in the range 72.0-93.0% (mean +/- SD for three occasions (%): 80.9 +/- 5.5, 81.4 +/- 7.8, and 78.9 +/- 1.0). The reliability of the method was tested against an HPLC procedure using in vivo-labeled rat's urine. The mean (+/- SD) percentage of urine radioactivity appearing as TMSe was 36.0 +/- 5.7% for the present and 36.2 +/- 6.6% for the HPLC method. The mean of deviations, as percentage of the HPLC method, was -0.03 +/- 8.8%. The linear regression equation for the two methods was y = -0.805 + 1.029x (r2 = 0.81). Excretion of TMSe was measured in urine samples from several persons (range: 0.18-0.37 micrograms Se/liter; mean +/- SD: 0.26 +/- 0.07, n = 9). One subject consumed three separate doses of unlabeled selenite on alternate days (Day 1, 197 micrograms Se; Day 3, 395; and Day 5, 592). For the first 24 h of each period, TMSe excretions (micrograms Se/24 h) were 0.24, 0.53, and 0.97, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Precipitation↗

Colorimetric determination of selenium in mineral premixes .

A method is described for determination of sodium selenite or sodium selenate in mineral-based premixes. It is based on the formation of intense-yellow piazselenol by Se(IV) and 3,3'-diaminobenzidine. Mineral premixes typically contain calcium carbonate as a base material and magnesium carbonate, silicon dioxide, and iron(III) oxide as minor components or additives. In this method, the premix is digested briefly in nitric acid, diluted with water, and filtered to remove any Iron(III) oxide. Ethylenediaminetetraacetic acid and HCl are added to the filtrate, which is heated to near boiling for 1 h to convert any selenate to selenite. After heating, the solution is buffered between pH 2 and 3 with NaOH and formic acid and treated with NH2OH and EDTA; any Se present forms a complex with 3,3'-diaminobenzidine at 60 degrees C. The solution is made basic with NH4OH, and the piazselenol is extracted into toluene. The absorbance of the complex in dried toluene is measured at 420 nm. The method was validated independently by 2 laboratories. Samples analyzed included calcium carbonate fortified with 100, 200, and 300 micrograms Se in the form of sodium selenite or sodium selenate, a calcium carbonate premix containing sodium selenite, a calcium carbonate premix containing sodium selenate, and a commercial premix; 5 replicates of each sample type were analyzed by each laboratory. Average recoveries ranged from 89 to 109% with coefficients of variation from 1.2 to 13.6%.

3,3'-Diaminobenzidine↗

Kinetics of Formation of Molybdenum Selenides from Modulated Reactants and Structure of the New Compound Mo(3)Se.

The kinetics of compound formation in the molybdenum-selenium system has been investigated using elementally modulated reactants to control overall composition and diffusion length. We observed the facile formation of MoSe(2) at low temperatures when the composition was above 50 atom % selenium. No evidence was found for the low-temperature formation of the other known stable molybdenum selenide, the cluster compound Mo(6)Se(8). When the composition of the initially modulated reactant was close to 25% selenium, a previously unreported compound was observed to form. This new compound, Mo(3)Se, has the A-15 crystal structure. The superconducting transition temperature appears to be very sensitive to composition, with a sharp resistive transition at 7 K in one sample and a sharp diamagnetic transition observed in a second sample at 2.2 K. The kinetics of phase formation in this system is analyzed in terms of nucleation kinetics.

Journal Article↗

Chemical form-dependent induction of hepatic zinc-thionein by arsenic administration and effect of co-administered selenium in mice.

Four arsenic compounds (m-arsenite, arsenate, methylarsonate (MMA), and dimethylarsinate (DMA) were administered to mice, either orally or by intraperitoneal injection, and the amounts of induced hepatic zinc-thionein (Zn-Th) were determined to investigate the chemical form dependency in metallothionein induction by arsenic. Several mice died within 24 h following intraperitoneal injection. The toxicity estimated from the lethality was in the order of m-arsenite greater than arsenate much greater than DMA approximately equal to MMA. Although all 4 arsenic compounds more or less induced Zn-Th following intraperitoneal injection, the dose of inorganic arsenic compounds observed to cause induction was one order lower than that of organic arsenic compounds. The induction of hepatic Zn-Th was also observed following oral administration, and inorganic arsenic compounds were again found to be more effective inducers via this route. To study the interactions of m-arsenite and selenite with regard to the amounts of Zn-Th induced, the two compounds were co-administered intraperitoneally. The amount of hepatic Zn-Th induced by the co-administration was one-fifth of that observed after selenite administration, and was almost the same as that after m-arsenite injection. Namely, when co-administered m-arsenite had the effect of lowering the level of Zn-Th induced following selenite administration, but the converse phenomenon was not observed.

Animals↗

Various functions of selenols and thiols in anaerobic gram-positive, amino acids-utilizing bacteria.

Electron transfer reactions for the reduction of glycine in Eubacterium acidaminophilum involve many selenocysteine (U)- and thiol-containing proteins, as shown by biochemical and molecular analysis. These include an unusual thioredoxin system (-CXXC-), protein A (-CXXU-) and the substrate-specific protein B of glycine reductase (-UXXCXXC-). Most probably a selenoether is formed at protein B by splitting the C-N-bond after binding of the substrate. The carboxymethyl group is then transferred to the selenocysteine of protein A containing a conserved motif. The latter protein acts as a carbon and electron donor by giving rise to a protein C-bound acetyl-thioester and a mixed selenide-sulfide bond at protein A that will be reduced by the thioredoxin system. The dithiothreitol-dependent D-proline reductase of Clostridium sticklandii exhibits many similarities to protein B of glycine reductase including the motif containing selenocysteine. In both cases proprotein processing at a cysteine residue gives rise to a blocked N-terminus, most probably a pyruvoyl group. Formate dehydrogenase and some other proteins from E. acidaminophilum contain selenocysteine, e.g., a 22 kDa protein showing an extensive homology to peroxiredoxins involved in the detoxification of peroxides.

Amino Acids↗