Showing papers on "Selenium published in 1992"

Selenite is a substrate for calf thymus thioredoxin reductase and thioredoxin and elicits a large non-stoichiometric oxidation of NADPH in the presence of oxygen.

Abstract: The thioredoxin system, comprising NADPH, thioredoxin reductase and thioredoxin reduces protein disulfides via redox-active dithiols. We have discovered that sodium selenite is a substrate for the thioredoxin system; 10 microM selenite plus 0.05 microM calf thymus thioredoxin reductase at pH 7.5 caused a non-stoichiometric oxidation of NADPH (100 microM after 30 min). In contrast, thioredoxin reductase from Escherichia coli showed no direct reaction with selenite, but addition of 3 microM E. coli thioredoxin also resulted in non-stoichiometric oxidation of NADPH, consistent with oxidation of the two active-site thiol groups in thioredoxin to a disulfide. Kinetically, the reaction was complex with a lag phase at low selenite concentrations. Under anaerobic conditions the reaction stopped after 1 mol selenite had oxidized 3 mol NADPH; the admission of air then resulted in continued consumption of NADPH consistent with autooxidation of selenium intermediate(s). Ferricytochrome c was effectively reduced by calf thymus thioredoxin reductase and selenite in the presence of oxygen. Selenite caused a strong dose-dependent inhibition of the formation of thiol groups from insulin disulfides with either the E. coli or calf-thymus thioredoxin system. Thus, under aerobic conditions selenite catalyzed, NADPH-dependent redox cycling with oxygen, a large oxygen-dependent consumption of NADPH and oxidation of reduced thioredoxin inhibiting its disulfide-reductase activity.

Reduction of Selenate and Selenite to Elemental Selenium by a Pseudomonas stutzeri Isolate.

Abstract: A Pseudomonas stutzeri isolate rapidly reduced both selenite and selenate ions to elemental selenium at initial concentrations of both anions of up to 48.1 mM. Optimal selenium reduction occurred under aerobic conditions between pH 7.0 and 9.0 and at temperatures of 25 to 35 degrees C. Reduction of both selenite and selenate was unaffected by a number of anions except for sulfite, chromate, and tungstate ions, which inhibited both growth and reduction.

Comparison of selenium and sulfur analogs in cancer prevention.

Abstract: Several organoselenium compounds have been shown to have powerful anticarcinogenic activity. In view of certain similarities between selenium and sulfur biochemistry, we have evaluated the chemopreventive efficacy of three pairs of analogs using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats. The compounds tested were selenocystamine/cysteamine, Semethylselenocysteine/S-methylcysteine, selenobetaine/sulfobetaine. In the first study, each agent was added to the basal AIN-76A diet and was given before and continued after DMBA treatment until the end. All three selenium compounds were active; a 50% inhibition was achieved at approximately 25 x 10(-6) mol/kg with Se-methylselenocysteine and selenobetaine and at approximately 40 x 10(-6) mol/kg with selenocystamine. In the sulfur series, only cysteamine and S-methylcysteine produced anticancer activity, and the levels required for comparable responses were 500- to 750-fold higher compared to the corresponding selenium analogs. Sulfobetaine was inactive even when present at near maximally tolerated levels. In the second study, Se-methylselenocysteine and S-methylcysteine were chosen for further examination during the initiation and post-initiation phases of mammary carcinogenesis. Se-Methylselenocysteine was effective when it was given either before or after DMBA administration. In contrast, S-methylcysteine was effective only after DMBA treatment. Thus, compared to the sulfur structural analogs, selenium compounds are much more active in cancer protection and may have a multi-modal mechanism in preventing cellular transformation as well as in delaying or inhibiting the expression of malignancy after carcinogen exposure.

Synthesis of 5-methylaminomethyl-2-selenouridine in tRNAs: 31P NMR studies show the labile selenium donor synthesized by the selD gene product contains selenium bonded to phosphorus

Abstract: An enzyme preparation from Salmonella typhimurium catalyzes the conversion of 5-methylaminomethyl-2-thiouridine in tRNAs to 5-methylaminomethyl-2-selenouridine when supplemented with selenide and ATP. Similar preparations from a Salmonella mutant strain carrying a defective selD gene fail to catalyze this selenium substitution reaction. However, supplementation of the deficient enzyme preparation with the purified selD gene product (SELD protein) restored synthesis of seleno-tRNAs. In the absence of the complementary enzyme(s), the SELD protein catalyzes the synthesis of a labile selenium donor compound from selenide and ATP. 31P NMR studies show that among the products of this reaction are AMP and a compound containing selenium bonded to phosphorus. The reaction is completely dependent on the addition of both selenide and magnesium. The dependence of reaction velocity on ATP concentration shows sigmoidal kinetics, whereas dependence on selenide concentration obeys Michaelis-Menten kinetics indicating a Km value of 46 microM for selenide.

Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population.

Abstract: OBJECTIVE: Severe selenium deficiency has been documented in northern Zaire, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN: Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS: Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT: Selenium status, thyroid function and urinary iodide were determined. RESULTS: After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/- 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH. CONCLUSION: Deiodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism.

Reduction of selenate and selenite to elemental selenium by Wolinella succinogenes

Abstract: Cultures of Wolinella succinogenes were adapted to grow in the presence of 1 mM or 10 mM . Both selenium salts were reduced to red, amorphous, elemental selenium but only after the culture reached ...

Selenium. Mechanistic aspects of anticarcinogenic action

Abstract: Selenium is increasingly recognized as a versatile anticarcinogenic agent. Its protective functions cannot be solely attributed to the action of glutathione peroxidase. Instead, selenium appears to operate by several mechanisms, depending on dosage and chemical form of selenium and the nature of the carcinogenic stress. In a major protective function, selenium is proposed to prevent the malignant transformation of cells by acting as a "redox switch" in the activation-inactivation of cellular growth factors and other functional proteins through the catalysis of oxidation-reduction reactions of critical SH groups of SS bonds. The growth-modulatory effects of selenium are dependent on the levels of intracellular GSH and the oxygen supply. In general, growth inhibition is achieved by the Se-mediated stimulation of cellular respiration. Selenium appears to inhibit the replication of tumor viruses and the activation of oncogenes by similar mechanisms. However, it may also alter carcinogen metabolism and protect DNA against carcinogen-induced damage. In additional functions of relevance to its anticarcinogenic activity, selenium acts as an acceptor of biogenic methyl groups, and is involved in the detoxification of metals and of certain xenobiotics. In its interactions with transformed cells at higher concentrations, it may induce effects ranging from metabolic and phenotypical changes, and partial renormalization to selective cytotoxicity owing to reversible or irreversible inhibition of protein and DNA synthesis. Selenium also has immunopotentiating properties. It is required for optimal macrophage and NK cell function. Its protective effects are influenced by synergistic and antagonistic dietary and environmental factors. The latter include a variety of toxic heavy metals and xenobiotic compounds, but they are also influenced by essential elements, such as zinc. The exposure to antagonistic factors must be minimized for the full expression of its anticarcinogenic potential.

The antioxidant status of patients with either alcohol-induced liver damage or myopathy

Abstract: The antioxidant status of alcoholic patients was assessed by direct measurement of the plasma antioxidants α-tocopherol and β-carotene and of selenium as a marker of glutathione peroxidase. Overall, the alcoholic group showed significant decreases in the mean plasma values of β-carotene, zinc and selenium when compared to the control subjects. When the patients were subdivided according to their liver histology, β-carotene showed a progressive decrease in plasma concentration with increasing liver damage, whereas α-tocopherol levels were only depleted in the patients with cirrhosis. There were significant decreases in the plasma concentrations of both α-tocopherol and selenium in all patients with alcoholic skeletal muscle myopathy, whereas patients with normal muscle biopsies showed adequate antioxidant status. Such results support a role for free radical-mediated damage in end organ injury, particularly myopathy, in alcohol misusers.

Structural characterization of selenosubtilisin by selenium-77 NMR spectroscopy

Abstract: The semisynthetic selenoenzyme selenosubtilisin catalyzes the reduction of alkyl hydroperoxides with concomitant oxidation of 3-carboxy-4-nitrobenzenethiol. To gain insight into the mechanism of this process, three oxidation states of the enzyme that are relevant to the redox cycle have been characterized by 77 Se NMR spectroscopy. Oxidation of selenosubtilsin with hydrogen peroxide in the absence of thiol yields a species whose spectrum consists of two peaks at 1188 and 1190 ppm, consistent with the selenium prosthetic group being in the seleninic acid oxidation state

Selenium mobilization in a surface coal mine, Powder River Basin, Wyoming, U.S.A.

Abstract: Elevated concentrations (0.6–0.9 mg/l) of selenium were detected in the groundwater of a small backfill area at a surface mine in the Powder River Basin, Wyoming. This report focuses on the source of selenium, its modes of occurrence in overburden deposits and backfill groundwater, and its fate. The immediate source of the selenium appeared to be the dissolution of preexisting soluble salts from the unsaturated zone of the overburden. The ultimate source of selenium was probably the oxidation of selenium-bearing pyrite in the geologic past. Overburden was placed partially in the saturated zone of the backfill where, upon resaturation, soluble salts dissolved in the groundwater. Water standing in the pit at the time of backfilling might have contributed to the elevated concentrations of selenium and other solutes. Selenium was found in an ash-rich coal and in clastic sediments in seven different modes of occurrence. The concentration of soluble selenium in the groundwater at this site has been decreasing since monitoring began in late 1982, and at the present rate of decrease, the concentration should drop below the State of Wyoming guideline of 0.05 mg/l for selenium in water intended for use by livestock by about mid-1992. The decrease in soluble selenium concentration may in part be due to microbially assisted reduction of selenate followed by sorption on clays and other sorbents.

Selenium retention in the organic matter of Swedish forest soils

Abstract: SUMMARY Fractions of selenium present in the soil profiles of three Swedish podzols were analysed using a sequential extraction scheme to characterize Se distribution among the organic and inorganic fractions. The process by which selenite deposited from the atmosphere is retained in a podzolic profile rich in organic matter was studied in a column experiment. Selenium present in organic fractions accounted for most of the Se extracted by Na4P2O7/NaOH. All soil organic matter fractions, particularly those in the B horizons, were considerably enriched with Se as compared with plant biomass. The most enriched fraction was that containing hydrophobic fulvates which had C to Se ratios ranging from 33 000 to 80 000. The distribution of Se among the organic fractions differed markedly from that of sulphur. Selenite applied to columns continuously for 67 d was fixed very rapidly upon entering the forest floor layers, with 77% being recovered in the top 2 cm of the forest floor after the experiment. In column leachates from the surface layers, C to Se ratios decreased progressively following Se application. No effect specifically related to Se application was observed for leachates and soil horizons underlying Bs1. The mechanism responsible for the efficient and rapid Se immobilization by organic matter is unknown.

Selenium deficiency and type II 5'-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine

Abstract: Selenium deficiency in rats is characterized by elevated serum T4 and decreased serum T3 concentrations, and low liver type I (5'D-I) and brain type II (5'D-II) iodothyronine 5'-deiodinase activities. These findings are partially explained by the demonstration that type I 5'D is a selenoprotein; however, 5'D-II does not contain selenium. Since 5'D-II varies inversely with serum T4 concentrations, and serum T4 is elevated in selenium deficiency, the decreased cerebrocortical 5'D-II activity may be secondary to the increased serum T4 levels. To determine the mechanism(s) by which selenium influences 5'D-II activity, we examined the effects of altered selenium intake on brain 5'D-II levels and enzyme turnover in euthyroid and thyroidectomized rats. Rats were fed a selenium-supplemented or selenium-deficient diet for 5 weeks from weaning; half of the animals were also thyroidectomized 3 weeks before death. Selenium deficiency was confirmed by decreased liver and brain glutathione peroxidase activities. In eut...

Inorganic element concentrations in cataractous human lenses.

Abstract: We evaluated the presence of calcium, potassium, zinc, copper, and selenium in human lenses (53 cataractous and 10 clear lenses). The determinations of these elements were done using atomic absorption spectrometry techniques, namely flame and flameless methods, after acidic digestion of the samples. Compared with the results obtained from samples of normal lenses (zinc, 16.5 +/- 2.5 mg/kg dry weight; copper, 0.53 +/- 0.08 mg/kg dry weight; selenium, 0.83 +/- 0.18mg/kg dry weight; potassium, 10,306 +/- 1232mg/kg dry weight, and calcium, 9.9 +/- 2.7mg/kg dry weight), the mean concentration values of the cataractous lenses showed some significant changes. Increases were found for zinc, copper, and calcium; the potassium concentration decreased. No significant changes occurred in selenium values. A positive correlation was found between zinc and copper concentrations (y = 0.030x + 0.007, r = .79). An inverse correlation was evident between calcium and potassium values (y = -0.097x + 1141, r = -.65).

Intestinal absorption of selenite, selenate, and selenomethionine in the rat

Abstract: Regional characteristics of intestinal absorption of selenocompounds under conditions of dietary selenium deficiency, intraluminal glutathione (GSH), and GSH depletion by buthionine [S,R] sulfoximine (BSO) treatment were studied. Absorption of 75Se from selenite, selenate, and selenomethionine (SeMet) was determined in ligated loops from duodena, jejuna, and ilea of selenium-deficient rats (0.009 ppm Se) or rats fed selenite-supplemented diets (0.20 ppm Se). Selenium deficiency had no effect on absorption of any selenocompound in any intestinal segment. SeMet was absorbed most rapidly from all segments. Selenate and selenite were most efficiently absorbed from the ileum. Substantial 75Se was retained within ileal tissue during selenite and SeMet absorption but was readily transferred to the body during ileal selenate uptake. Luminal GSH (50 μmol/L) had no effect on mucosal GSH levels nor on selenite uptake. BSO treatment decreased tissue GSH levels to 37%–54% of controls depressing 75Se-selenite uptake to 55%–64% and transfer to 29%–34% of controls. 75Se-SeMet absorption was not altered by 1 mmol/L intraluminal GSH or by mucosal GSH depletion. No evidence for homeostatic regulation of selenium absorption was obtained. Intracellular GSH appears to be involved in transepithelial transport of 75Se-selenite but not 75Se-SeMet.

Direct Observation of Intramolecular Interaction between a Divalent Selenium and a Tertiary Amine by Means of Single Crystal X-Ray Analysis and NMR Spectroscopy

Abstract: Intramolecular interaction between a divalent selenium and a tertiary amino moiety has been observed in the solid state for 2,2′-diselenobis(N-cyclohexyl-N-methylbenzyl amine) (1). A similar interaction between an electrophilic selenium and a tertiary amine has also been observed in solution for the corresponding selenenyl bromide (6).

Metabolism of selenate and selenomethionine by a selenium-deficient population of men in China

Abstract: Twenty young Chinese men (ages 18–40 with a mean age of 29 years) living in a selenium deficient area of China (Dechang county. Sichuan province) were selected, divided into two groups, and provided with 200 μg selenium daily for 1 year as either selenate or selenomethionine (Semet). Blood and 24-hour urine samples were collected initially, after 1 month of supplementation and subsequently at bimonthly intervals. Selenium increased in both plasma and erythrocytes at a significantly faster rate in deficient men taking Semet than in those taking selenate. Glutathione peroxidase (GSH-Px) activity increased in both plasma and erythrocytes up to 4 months where a plateau was reached, but there were no differences in this activity between these two supplemental groups. The percentage of selenium associated with GSH-Px was significantly lower in plasma and erythrocytes in men taking. Semet than in those taking selenate. Gel filtration chromatography revealed two selenium-containing peaks in plasma of men taking Semet but mostly one in plasma from men taking selenate. Urinary excretion of selenium gradually increased throughout this study, but there were no differences in the excretion of total selenium or trimethylselenium (TMSe) between the two treatment groups. The TMSe content ranged between 1%–2.5% of total selenium in both groups.

Effect of selenium deficiency on hepatic type I 5-iodothyronine deiodinase activity and hepatic thyroid hormone levels in the rat.

Abstract: Selenium deficiency in rats for a period of up to 6 weeks inhibited both the production of 3,3',5-tri-iodothyronine (T3) from thyroxine (T4) (5'-deiodination) and also the catabolism of T3 to 3,3'-di-iodothyronine (5-deiodination) in liver homogenates. The hepatic stores of T3 were decreased by only 8% in selenium deficiency, despite the T3 production rate from T4 being only 7% of the rate found in selenium-supplemented rats. Hepatic glutathione S-transferase (GST) activity was increased in both hypothyroidism and selenium deficiency, but apparently by different mechanisms, since mRNA expression for this family of enzymes was lowered by hypothyroidism and increased in selenium deficiency. It is concluded that, since both T3 production and catabolism are inhibited by selenium deficiency, there is little change in hepatic T3 stores, and therefore the changes in the activity of certain hepatic enzymes, such as GST, that are found in selenium deficiency are not the result of tissue hypothyroidism.

Utilization of two different chemical forms of selenium during lactation using stable isotope tracers: an example of speciation in nutrition

Abstract: The bioavailability and metabolism of different chemical species of mineral nutrients in the diet are receiving much attention from research nutritionists. In order to make scientifically based recommendations for mineral intakes, the chemical form of the mineral, with its specific absorption, utilization and retention, needs to be considered. Selenium is an example of an essential nutrient that is consumed in several different chemical forms, hence information is needed on the bioavailability and metabolism of each form before recommendations for dietary intakes can be made. A valuable tool for research on bioavailability and metabolism in humans is stable isotope tracers. When there are more than two stable isotopes available, as with selenium, stable isotope methodology allows the comparison of the utilization of different chemical forms of the nutrient simultaneously in in vivo studies. As an example of speciation questions addressed by nutritionists, a study is described that simultaneously evaluated utilization (absorption, retention and appearance in milk and blood) of two different chemical forms of selenium (selenite and selenomethionine) in lactating, non-lactating and never pregnant women using stable isotope tracers. All three groups of women had similar selenium status at the start of the study. Significantly more selenium from selenomethionine than from selenite was absorbed and appeared in the plasma in all groups. Milk contained more selenium from apparently absorbed selenomethionine than from selenite. All groups retained significantly more selenium from selenomethionine than from selenite; lactating women retained more selenium from selenite than did the other two groups, suggesting that milk losses may be partially compensated by enhanced retention of dietary selenium as selenite. Absorption and retention of selenium from selenomethionine in lactating women did not appear to be different from the other groups. The different chemical forms of selenium are metabolized differently among different physiological groups of women.

Evidence for intestinal release of absorbed selenium in a form with high hepatic extraction.

Abstract: Selenium is readily absorbed from the gastrointestinal tract and utilized for synthesis of selenoproteins. Roles of intestine, liver, and selenoprotein P in this process were evaluated. Rats were given 75Se-selenite by stomach tube, and distribution of 75Se was followed for 3 h. A high portal vein plasma-to-hepatic vein plasma ratio of 75Se 15 min after 75Se administration and earlier uptake by liver than by other tissues indicated avid hepatic extraction of absorbed selenium from portal vein blood. The results of gel filtration of plasma taken 15 min after 75Se administration suggested that the 75Se was in the form of small molecules with some affinity for protein. Immunoprecipitation studies using plasma indicated that 75Se began to appear in selenoprotein P between 15 and 30 min after intragastric administration. To evaluate the role of the liver in the fate of absorbed selenium, rats with portacaval shunts, in which absorbed selenium bypasses the liver, were compared with sham-operated rats. After intragastric administration of selenium, uptake by the liver and incorporation into selenoprotein P were diminished in rats with portacaval shunts but kidney uptake and urinary excretion were increased. This suggests that hepatic extraction of absorbed selenium from portal vein blood decreases its entrance into the systemic circulation. The results of this study indicate that intestine releases absorbed selenium into portal blood in a small-molecule form, designated A-Se, which is highly extracted by the liver. The liver takes up A-Se better than other tissues because of a high extraction capacity and the fact that it is the first organ through which the blood from the intestine passes.

Influence of intracellular glutathione on selenite-mediated growth inhibition of canine mammary tumor cells.

Abstract: The present studies demonstrate that the ability of supplemental selenite to alter the in vitro growth of canine mammary tumor cell line 13 was dependent on the quantity and duration of selenium exposure and on the culture density. Exposure to 3.2 µm selenite did not significantly alter growth but led to an increase in intracellular glutathione (GSH). The severity of growth inhibition between 3.2 and 9.6 µm selenite was dependent on the duration of exposure and culture density. The toxicity of selenite generally increased as the culture density increased. Likewise, changes in intracellular GSH were dependent on the quantity and duration of selenite exposure and the culture density. Depressing intracellular GSH by increasing the culture density or by incubating with buthionine sulfoximine; a specific inhibitor of γ-glutamyl cysteine synthetase, increased the severity of growth inhibition caused by selenite and markedly increased cellular retention of selenium. Nevertheless, marked cellular retention of selenium did not occur until growth was inhibited by more than 50%. The present studies revealed that the log of the molar ratio of GSH to selenium correlated negatively with the severity of growth inhibition ( P < 0.0001). These studies suggest that cellular toxicity of selenite is dependent on the regulation of the GSH:selenium ratio. An inability to regulate this ratio likely leads to the accumulation of toxic seleno compounds.

Heavy metal and selenium concentrations in black skimmers (Rynchops niger) : gender differences

Abstract: Most studies of heavy metals and selenium have not examined or have failed to find differences in concentrations in the tissues of birds as a function of size or sex. Heavy metal and selenium concentrations were analyzed in breast feathers of adult black skimmers Rynchops niger, a species with marked sexual size dimorphism in which males average 35% heavier than females. Females had significantly higher concentrations of lead and cadmium than males, but there were no gender differences in mercury, selenium, chromium, manganese, and copper despite the marked sexual dimorphism in body size. There were no significant correlations of bird weight or wing length and metal and selenium concentrations, and few correlations among metal and selenium concentrations in the feathers.