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Thermally oxidized dietary fats increase plasma thyroxine concentrations in rats irrespective of the vitamin E and selenium supply.

A recent study demonstrated that feeding a diet with a thermally oxidized fat increases the concentration of thyroxine in plasma of miniature pigs. This study was undertaken to investigate whether the effect of thermally oxidized fats on plasma thyroid hormones is influenced by the supply of vitamin E or selenium. Two experiments were conducted using male Sprague-Dawley rats. The first experiment included eight groups of rats fed diets with either fresh fat or three different types of oxidized fat prepared by heating at 50 degrees C, 105 degrees C or 190 degrees C for 42 d. The diets contained either 25 or 250 mg alpha-tocopherol equivalents per kg. The second experiment included four groups of rats fed diets with fresh fat or oxidized fat heated at 55 degrees C, containing either 70 or 570 microg selenium per kg for 56 d. Rats fed all types of oxidized fats had higher concentrations of free and total thyroxine in plasma than rats fed the equivalent diets with fresh oil; the concentrations of triiodothyronine and thyroid-stimulating hormone did not differ between rats fed fresh and those fed oxidized fats. The effect of the oxidized fat on the plasma thyroxine concentration was completely independent of the supply of vitamin E (expt. 1) and the supply of selenium (expt. 2). Our results confirm that oxidized dietary fats raise the plasma thyroxine concentration and show that this phenomenon is independent of the vitamin E and selenium status.

Animals↗

Coordination Chemistry of 2,2'-Dipyridyl Diselenide: X-ray Crystal Structures of PySeSePy, [Zn(PySeSePy)Cl(2)], [(PySeSePy)Hg(C(6)F(5))(2)], [Mo(SePy)(2)(CO)(3)], [W(SePy)(2)(CO)(3)], and [Fe(SePy)(2)(CO)(2)] (PySeSePy = C(5)H(4)NSeSeC(5)H(4)N; SePy = [C(5)H(4)N(2-Se)-N,Se]).

The coordination chemistry of 2,2'-dipyridyl diselenide (PySeSePy) (2) (C(10)H(8)N(2)Se(2)) has been investigated and its crystal structure has been determined (monoclinic, P2(1)/c, a = 10.129(2) Å, b = 5.7332(12) Å, c = 19.173(3) Å, beta = 101.493(8) degrees, Z = 4). In metal complexes the ligand was found to coordinate in three different modes, as also confirmed by X-ray structure determination. N,N'-coordination was found in the zinc complex [Zn(PySeSePy)Cl(2)] (3) (C(10)H(8)Cl(2)N(2)Se(2)Zn, triclinic, P&onemacr;, a = 7.9430(10) Å, b = 8.147(2) Å, c = 11.999(2) Å, alpha = 93.685(10) degrees, beta = 107.763(10) degrees, gamma = 115.440(10) degrees, Z = 2) and Se,Se'-coordination in the adduct of the ligand with bis(pentafluorophenyl)mercury(II) [PySeSePyHg(C(6)F(5))(2)] (5) (C(10)H(8)F(10)HgN(2)Se(2), monoclinic, P2(1)/n, a = 7.7325(10) Å, b = 5.9974(14) Å, c = 25.573, beta = 98.037(10) degrees, Z = 2), which however displays only weak interactions between selenium and mercury. The reaction of the ligand with norbornadiene carbonyl complexes of molybdenum and tungsten leads to reductive cleavage of the selenium-selenium bond with oxidation of the metal center and concomitant addition of the resulting selenolate to the metal carbonyl fragment. Thus the 7-coordinate complexes [Mo(SePy)(2)(CO)(3)] (6) (C(13)H(8)MoN(2)O(3)Se(2), monoclinic, P2(1)/n, a = 9.319(3) Å, b = 12.886(5) Å, c = 13.231(6) Å, beta = 109.23(3) degrees, Z = 4) and [W(SePy)(2)(CO)(3)] (7) (C(13)H(8)N(2)O(3)Se(2)W, monoclinic, P2(1)/n, a = 9.303(2) Å, b = 12.853(2) Å, c = 13.232(2) Å, beta = 109.270(10) degrees, Z = 4) were obtained. The same N,Se-coordination pattern emerges from the reaction of [Fe(2)(CO)(9)] with (2) leading to [Fe(SePy)(2)(CO)(2)] (8) (C(12)H(8)FeN(2)O(2)Se(2), monoclinic, P&onemacr;, a = 8.6691(14) Å, b = 12.443(2) Å, c = 14.085(2) Å, alpha = 105.811(10) degrees, beta = 107.533(8) degrees, gamma = 92.075(10) degrees, Z = 4).

Journal Article↗

Vitamin B12 responses to cobalt pellets in beef cows.

OBJECTIVE: To assess the effectiveness of cobalt pellets in maintaining adequate vitamin B12 in beef cows on pasture of low cobalt content. DESIGN: A field experiment in a herd grazing cobalt deficient pasture. ANIMALS: Mature Murray Grey cows. PROCEDURE: Cows were given a single oral dose of 0, 1, 2 or 4 cobalt pellets (30 g pellets containing 30% by weight cobaltic oxide) with a selenium pellet and a grub screw. Samples of blood, liver, faeces and milk for chemical analysis were collected at intervals over a period of 2 years after treatment. RESULTS: A single cobalt pellet raised liver vitamin B12 concentration of cows above that of untreated cows for at least 28 weeks, and 2 or 4 pellets for 57 weeks. Plasma vitamin B12 concentration was an unreliable indicator of the effectiveness of cobalt pellet therapy. Milk vitamin B12 and faecal cobalt concentrations increased in response to cobalt pellet therapy. CONCLUSION: These studies show that one cobalt pellet will prevent vitamin B12 inadequacy in beef cows for between 28 and 57 weeks; two or four pellets will prevent inadequacy for 57 to 75 weeks. Milk vitamin B12 concentration may be a useful indicator of the effectiveness of cobalt pellets in increasing the vitamin B12 supply in lactating cows.

Animal Feed↗

Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.

To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology.

Animals↗

Factors influencing the stability of heme and ferrochelatase: role of oxygen.

Ferrochelatase (EC 4.99.1.1) catalyzed heme synthesis is best accomplished in an anaerobic environment. Factors responsible for this phenomenon are not fully understood. Oxygen sensitivity of this reaction may be due to (a) oxidation of essential thiol groups on the enzyme, (b) oxidation of ferrous ions, or (c) the formation of hydrogen peroxide. These possibilities were investigated using rat liver ferrochelatase preparations and a continuous, dual-wavelength assay. Dithiothreitol and ascorbic acid stimulated the ferrochelatase reaction whereas GSH was not as effective. Addition of GSSG had little influence on the enzyme reaction. Total ferrochelatase activity in the assay remained unaffected at the end of the incubation and inclusion of glutathione peroxidase did not alter these results. Thus, ferrochelatase itself was not inactivated by oxidation. In selenium-deficient rats, the mitochondrial ferrochelatase levels were maintained even when glutathione peroxidase activity was significantly depleted. However, glutathione peroxidase very effectively inhibited the thiol-dependent aerobic degradation of heme. These results suggested that autoxidation of heme and of ferrous ions to the unusable ferric form largely contribute toward the oxygen sensitivity of the ferrochelatase reaction in vitro.

Aerobiosis↗

Ovine white-liver disease (OWLD) in Norway: clinical symptoms and preventive measures.

During 6 years, altogether 458 twin lambs of the Dala and Rygia breeds with their dams were put on ovine white-liver disease (OWLD) pastures which were moderately, heavily or not cobalt fertilized, or on control pastures 15 km apart. Groups of lambs were untreated, regularly dosed with Co sulphate or vitamin B12, dosed with Co pellets, copper oxide needles (CuO), selenium pellets or Co-Se-Cu glass boli, or had access to Co enriched salt lick. Clinical symptoms in untreated lambs included varying degree of reduced weight gain or loss of weight appearing after 6-12 weeks on pasture, at an age of 10-15 weeks. Additional symptoms were seen 2-4 weeks later, including inappetence, listlessness, and often serous eye discharge and crusty ears. Of the untreated lambs on OWLD pastures 18% died or were eutanized because of OWLD. The condition was preventable by Co or B12 administration, which yielded an average increase of mid Sept. live weights of between 8 and 17 kg. Co fertilization of pastures, use of Co enriched salt lick, or dosing with Co pellets are recommended under practical circumstances. The lambs grazing control pastures were on average 17 kg heavier by mid Sept. than the OWLD lambs. They showed some weight increase on extra Co supply.

Animals↗

Forms and distribution of selenium at different depths and among particle size fractions of three Taiwan soils.

The bioavailability of selenium in soils for plants depends more on its forms than on its total concentration. The purpose of the present study was to examine the solid-phase forms of selenium at different depths of three soil series representing major farming soil groups in Taiwan as well as the amounts of selenium in sand, silt and clay fractions of the soils. The study was conducted by means of sequential extraction to obtain the amounts of selenium and the distribution of various solid-phase forms of selenium at different depths of Pinchen (121 degrees 11(')E, 24 degrees 55(')N), Toulun-Sheto (120 degrees 55(')E, 24 degrees 50(')N), and Chunliao (120 degrees 25(')E, 23 degrees 57(')N) soil series. The amounts of metal oxide-bound form of selenium in the three soil series were the largest, with those of Pinchen and Toulun-Sheto soil series exceeding 50% of the total amounts of selenium and that of Chunliao soil series maintained at 30-40%. In the Pinchen and Toulun-Sheto soil series, the amounts of selenium in clay fractions were the largest, with a significant difference between the clays with and without metal oxides and organic matter removed. The amounts of selenium remained high in silt and/or sand fractions of the Chunliao soil series with metal oxides and organic matter removed. Metal oxide and organic matter contents of the three soil series mainly affect the amounts of various solid-phase forms of selenium and their distribution in different depths and particle size fractions of the soils. This observation of selenium associated with soil constituents was in good agreement with the results of the adsorption of selenite and selenate by the three soil series.

Adsorption↗

Toxicity, bioavailability and metal speciation.

1. Environmental toxicology emphasizes the difference from traditional toxicology in which pure compounds of interest are added to purified diets, or injected into the test animals. When the objective is to study the fate and effects of trace elements in the environment, knowledge of the speciation of the elements and their physico-chemical forms is important. 2. Cadmium salts such as the sulfides, carbonates or oxides, are practically insoluble in water. However, these can be converted to water-soluble salts in nature under the influence of oxygen and acids. Chronic exposure to Cd is associated with renal toxicity in humans once a critical body burden is reached. 3. The solubility of As(III) oxide in water is fairly low, but high in either acid or alkali. In water, arsenic is usually in the form of the arsenate or arsenite. As(III) is systemically more poisonous than the As(V), and As(V) is reduced to the As(III) form before exerting any toxic effects. Organic arsenicals also exert their toxic effects in vivo in animals by first metabolizing to the trivalent arsenoxide form. Some methyl arsenic compounds, such as di- and trimethylarsines, occur naturally as a consequence of biological activity. The toxic effect of arsenite can be potentiated by dithiols, while As has a protective effect against the toxicity of a variety of forms of Se in several species. 4. Selenium occurs in several oxidation states and many selenium analogues of organic sulfur compounds exist in nature. Selenium in selenate form occurs in alkaline soils, where it is soluble and easily available to plants. Selenite binds tightly to iron and aluminum oxides and thus is quite insoluble in soils. Hydrogen selenide is a very toxic gas at room temperature. The methylated forms of Se are much less toxic for the organism than selenite. However, the methylated Se derivatives have strong synergistic toxicity with other minerals such as arsenic. 5. Aquatic organisms absorb and retain Hg in the tissues, as methylmercury, although most of the environmental Hg to which they are exposed is inorganic. The methylmercury in fish arises from the bacterial methylation of inorganic Hg. Methylmercury in the human diet is almost completely absorbed into the bloodstream. The nervous system is the principal target tissue affected by methylmercury in adult human beings, while kidney is the critical organ following the ingestion of Hg(II) salts.

Animals↗

Internally stabilized selenocysteine derivatives: syntheses, 77Se NMR and biomimetic studies.

Selenocystine ([Sec]2) and aryl-substituted selenocysteine (Sec) derivatives are synthesized, starting from commercially available amino acid l-serine. These compounds are characterized by a number of analytical techniques such as NMR (1H, 13C and 77Se) and TOF mass spectroscopy. This study reveals that the introduction of amino/imino substituents capable of interacting with selenium may stabilize the Sec derivatives. This study further suggests that the oxidation-elimination reactions in Sec derivatives could be used for the generation of biologically active selenols having internally stabilizing substituents.

Biomimetics↗

Increased myocardial and hepatic iron concentration in pigs with microangiopathy (mulberry heart disease) as a risk factor of oxidative damage.

The role of iron was evaluated in pigs that died suddenly of microangiopathy (mulberry heart disease) characterized by myocardial and endothelial cell damage and capillary microthrombosis. Myocardial iron concentration (mean +/- SD) in pigs with microangiopathy (416 +/- 87 micrograms/g, dry weight) was significantly (p less than 0.001) higher than in pigs with other diseases (294 +/- 93 micrograms/g) and in healthy slaughter pigs (231 +/- 43 micrograms/g). Similarly, hepatic iron concentration in pigs with microangiopathy (1,211 +/- 254 micrograms/g) was significantly (p less than 0.001) higher than in pigs with other diseases (873 +/- 296 micrograms/g) and in healthy slaughter pigs (831 +/- 284 micrograms/g). The results indicate that myocardial and hepatic iron concentration was increased in pigs with microangiopathy. Increased myocardial and hepatic iron concentration might have promoted oxidative stress in selenium-vitamin E-deficient pigs and thus contributed to the development of oxidative damage.

Animals↗

Protection by vitamin E selenium, trolox C, ascorbic acid palmitate, acetylcysteine, coenzyme Q, beta-carotene, canthaxanthin, and (+)-catechin against oxidative damage to liver slices measured by oxidized heme proteins.

Male SD rats were fed a vitamin E- and selenium-deficient diet, a diet supplemented with vitamin E and selenium, and diets supplemented with vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, beta-carotene, canthaxanthin, coenzyme Q0, coenzyme Q10, and (+)-catechin. Liver slices were incubated at 37 degrees C with and without CBrCl3, t-butyl-hydroperoxide, Fe+2, or Cu+2. The effect of antioxidant nutrients on the oxidative damage to rat liver was studied by measurement of the production of oxidized heme proteins (OHP) during the oxidative reactions. Diet supplemented with vitamin E and selenium showed a strong protection against heme protein oxidation compared to the antioxidant-deficient diet. Furthermore, increasing the diversity and quantity of antioxidants in the diets provided significantly more protection.

Acetylcysteine↗

Selenium speciation analysis using inductively coupled plasma-mass spectrometry.

Selenium exists in several oxidation states and a variety of inorganic and organic compounds, and the chemistry of selenium is complex in both the environment and living systems. Selenium is an essential element at trace levels and toxic at greater levels. Interest in speciation analysis for selenium has grown rapidly in this last decade, especially in the use of chromatographic separation coupled with inductively coupled plasma-mass spectrometry (ICP-MS). Complete characterization of selenium compounds is necessary to understand selenium's significance in metabolic processes, clinical chemistry, biology, toxicology, nutrition and the environment. This review describes some of the essential background of selenium, and more importantly, some of the currently used separation methodologies, both chromatographic and electrophoretic, with emphasis on applications of selenium speciation analysis using ICP-MS detection.

Chromatography, Gas↗

A new kinetic model for the mode of action of soluble and membrane-immobilized glutathione peroxidase from bovine erythrocytes--effects of selenium.

Kinetic studies on the oxidative reaction of glutathione by hydrogen peroxide were performed using soluble and membrane-bound ox erythrocyte glutathione peroxidase of various types. The effects of organic and inorganic selenium on the glutathione peroxidase activity were also examined. The kinetic behaviour of the enzyme was investigated using a coupled reaction within a relatively large range of hydrogen peroxide and glutathione concentrations. Non-parallel double-reciprocal plots were obtained which suggested that a sequential ordered rather than a ping-pong mechanism was involved. Similar results were obtained with soluble and membrane-bound enzyme, whatever the type of crosslinking used. Crosslinking was performed on a nylon support using various alkylating agents and bifunctional molecules. With all three types of immobilized enzyme thus obtained, a slight but significant increase in the Km was observed. The effects of selenium were then studied. Using soluble enzyme, a slight increase in the activity was observed in the presence of inorganic selenium (sodium selenite) but not with organic selenium (seleno-L-methionine). Inorganic selenium alone was also found to have a slight effect on the membrane-bound enzyme. An increase in the catalytic efficiency was observed when glutathione peroxidase was bound using lysine as the bifunctional agent and either glutaraldehyde or triethyloxonium tetrafluoroborate as the reticulation agent, after a three-month period of incubation.

Animals↗

Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy.

OBJECTIVE: Our objective is to examine how selenium (Se) supplementation influences oxidative stress (malondialdehyde) and the glutathione peroxidase system in patients with ovarian cancer undergoing chemotherapy. MATERIAL: The study group included 31 patients with ovarian cancer undergoing chemotherapy receiving the drug Protecton Zellactiv (Smith Kline Beecham, Fink Naturarznei GmbH, Germany), two capsules, four times daily (200 microg). RESULTS: Following the Se supplementation in a daily dose of 200 microg, the concentration of this microelement in serum (P < 0.05) and hair (P < 0.05) was significantly higher than in the control group. It has also been found that Se concentration in serum was significantly increased after 2 (P < 0.0000) and 3-months' (P < 0.0000) length of supplementation, as compared to the values after 1 month. In the hair of patients receiving this supplementation, an insignificantly higher concentration of this microelement was found after 2 (NS) and 3 months (NS) in comparison to the concentration after 1 month. The patients with ovarian cancer undergoing chemotherapy and receiving Se showed a significant increase in the activity of GSH-P(x) in erythrocytes after 2 months' (P < 0.0015) and 3 months' (P < 0.0038) supplementation. An increase of the concentration of malondialdehyde (MDA) following the administration of Se after 2 months (P < 0.0363) and 3 months (P < 0.0489) was found to be significant. The increase of MDA calculated into platelet count was found to be significant after 3 months (P 0.0477) of Se supplementation. Se administration for 3 months resulted in the significant increase of white blood cells (WBC) (P < 0.0001). After 2 and 3 months of Se administration, a significant decrease of hair loss (P < 0.0000; P < 0.0392, respectively), flatulence (P < 0.0000; P< 0.0000), abdominal pain (P < 0.0006; P < 0.0202), weakness (P < 0.0001; P < 0.0000), malaise (P < 0.0017; P < 0.0000), loss of appetite (P < 0.0000; P < 0.0000) was stated. CONCLUSION: As a result of this clinical trial, we conclude that there are beneficial effects caused by ingesting selenium, as a supportive element in chemotherapy.

Aged↗

Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells.

Oxidant stress plays an important role in the etiology of vascular diseases by increasing rates of endothelial cell apoptosis, but few data exist on the mechanisms involved. Using a unique model of oxidative stress based on selenium deficiency (-Se), the effects of altered eicosanoid production on bovine aortic endothelial cells (BAEC) apoptosis was evaluated. Oxidant stress significantly increased the immediate oxygenation product of arachidonic acid metabolized by the 15-lipoxygenase pathway, 15-hydroxyperoxyeicosatetraenoic acid (15-HPETE). Treatment of -Se BAEC with TNFalpha/cyclohexamide (CHX) exhibited elevated levels of apoptosis, which was significantly reduced by the addition of a specific 15-lipoxygenase inhibitor PD146176. Furthermore, the addition of 15-HPETE to PD146176-treated BAEC, partially restored TNF/CHX-induced apoptosis. Increased exposure to 15-HPETE induced apoptosis, as determined by internucleosomal DNA fragmentation, chromatin condensation, caspase-3 activation, and caspase-9 activation, which suggests mitochondrial dysfunction. The expression of Bcl-2 protein also was decreased in -Se BAEC. Addition of a caspase-9 inhibitor (LEHD-fmk) completely blocked 15-HPETE-induced chromatin condensation in -Se BAEC, suggesting that 15-HPETE-induced apoptosis is caspase-9 dependent. Increased apoptosis of BAEC as a result of oxidant stress and subsequent production of 15-HPETE may play a critical role in a variety of inflammatory based diseases.

Animals↗

Selenium modifies glutathione peroxidase activity and glutathione concentration in mice exposed to ozone-provoked oxidative stress.

The aim of this study was to show the direct effect of selenium on glutathione peroxidase (GSH-Px) activity and GSH/GSSG concentrations in 3- and 6-month-old mice. An ozone-oxygen mixture was used to provoke an oxygen stress. To measure the Se-effect mice were gavaged with sodium selenite. GSH-Px activity and total glutathione concentrations were determined in serum and in the postnuclear fraction of liver and lungs. Additionally glutathione concentrations were determined in whole blood. Both ozone and selenium, administered separately, reduced GSH-Px activity in lungs of 6-month-old animals, while in young mice an opposite effect of Se was observed. Ozone administered jointly with Se did not influence GSH-Px activity in 6-month-old mice, while in young, 3-month-old mice, a stimulatory effect in lungs was observed. There were no significant changes in GSH-Px activity in the liver of 6-month-old mice, but the stimulatory effect occurred in young mice treated with Se and Se & ozone jointly. In young mice, ozone (also ozone with Se) augmented glutathione concentrations. The response to ozone and selenium strictly depended on age and the antagonism between selenium and ozone was observed only in a few cases.

Animals↗