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[The clinical significance of selenium deficiency in patients from the Samara region with cardiovascular diseases and its correction with the preparation Selena].

Selenium concentration in blood, glutathionperoxidase (GSH-Px) activity in erythrocytes and lipid peroxides in plasma were studied in patients with ischemic heart disease, hypertrophic (HCMP) and dilated cardiomyopathy (DCMP). Patients with IHD, HCMP and DCMP revealed depressed activity of GSH-Px with activation of lipid peroxides associated with lowered selenium content in blood. The selenium content in blood was lower in patients with severe forms of IHD Daily intake of 300 micrograms selenium with "Selena" during a month increases selenium concentration by 71% in patients with IHD and DCMP. This increase change inversely with primary selenium concentration in plasma. Plasma Malone dialdehyde concentration decreased by 17%. The results obtained suggest participation of selenium in cardiomyopathy and IHD pathogenesis, thus forming a basis for selecting the patients with selenium deficiency for its further correction with "Selena."

Adult↗

Serum selenium concentration in patients with liver cirrhosis and hepatocellular carcinoma.

The aim of the study was to investigate the serum selenium concentration in patients with liver cirrhosis and hepatocellular carcinoma. A total of 59 patients, 49 with liver cirrhosis and 10 with liver cirrhosis and coexistent hepatocellular carcinoma, as well as 202 healthy volunteers entered the study. In the patients with liver cirrhosis and in those with liver cirrhosis and coexistent hepatocellular carcinoma, serum selenium concentrations were significantly lower (39.28 +/- 13.99 and 42.00 +/- 10.59 g/L, respectively), when compared to the group of healthy volunteers (66. 79 +/- 9.13 g/L) (p < 0.001). There was no significant difference in serum selenium concentrations between the two patient groups. In the group of patients with liver cirrhosis positive correlation was found between serum selenium and albumin concentrations, and negative correlation between serum selenium and bilirubin (p < 0.05 and p < 0.01, respectively). There was no correlation of serum selenium concentration with fibrinogen and prothrombin time. Results of the study suggested the possible important nutritive and protective role of selenium in the patients with liver cirrhosis and coexistent hepatocellular carcinoma, as well as the potential need of selenium supplementation in these patients.

Aged↗

Selenium: a quest for better understanding.

Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies indicate an association between low nutritional selenium status and increased risks of cardiomyopathy, cardiovascular disease, and carcinogenesis in various sites of the body. The role of selenium supplementation in the prevention and treatment of AIDS-related pathology has been considered. Selenoproteins discovered in mammalian cells may account for the essentiality of selenium in the body's antioxidant defense; thyroid hormone function; immune system function, particularly the cellular immunity; formation of sperm; and functioning of the prostate gland. The seleno-organic compounds, primarily L-(+)-selenomethionine, generally are recognized as safe and effective forms of selenium supplementation. The nutritionally recommended dose of elemental selenium is estimated at 50 to 200 micrograms [corrected] per day. There is, however, increased discussion of a pharmacological dose of selenium, significantly higher than the nutritional dose of the microelement, to treat active conditions. One way of increasing the tissue levels of selenium is to combine its ingestible form with a nutrient bioavailability enhancing compound.

Humans↗

Plasma selenium in healthy man before and after nutratherapy.

Females (n = 28) and males (n = 39) had their plasma analysed for selenium (Se), ubiquinone, alpha-tocopherol (vitamin E), the essential fatty acid (EFA) classes: omega-3 (omega-3, n-3) and omega-6 (omega-6, n-6) fatty acids. Selenium averaged 0.99 +/- 0.03 mumol/l and was positively related to plasma ubiquinone, alpha-tocopherol and the EFA index: the omega-6/omega-3 ratio. Food supplements (nutratherapy) with the lipophilic antioxidants ubiquinone and alpha-tocopherol (Q + E) had no effect on selenium but the addition of omega-3 fatty acids as a fish oil concentrate (Q + E + n-3) had (1.12 +/- 0.05 mumol/l, + 36%, p < 0.001). (Q + E) and (Q + E + n-3) with the addition of selenium (200 micrograms or 2.5 mumol a day) raised selenium but not higher than (Q + E + n-3) itself (1.17 +/- 0.12 mumol/l, p < 0.05). After (Q + E) alone, selenium was related as at base-line to both ubiquinone and alpha-tocopherol but not to any marker for EFA. After (Q + E + n-3), selenium was only related to ubiquinone. An unsatisfactory alpha-tocopherol nutratherapy was suggested as the explanation. EFA or markers for EFA were in no situation related to plasma selenium.

Adult↗

Protective effects of selenium against mercury toxicity in cultured Atlantic spotted dolphin (Stenella plagiodon) renal cells.

Marine mammals are known for their low susceptibility to mercury toxicity, and selenium may play a role in this protection against mercury intoxication. To gain insight into mechanisms by which selenium might inhibit mercury toxicity in cetacean cells, we investigated the effects of sodium selenite on cell proliferation and cell death (including apoptosis, oncosis, and necrosis) of control and mercuric chloride-treated Atlantic spotted dolphin renal cells (Sp1K cells). Concurrent exposure to 80 microM Na2SeO3 provided full protection against the decrease in cell proliferation induced by 20 microM HgCl2. Pretreatment with Na2SeO3 increased the protective effects of selenium administered later in conjunction with mercury, but pretreatment alone did not provide protection against mercury given alone. Furthermore, Na2SeO3 administered after the exposure to HgCl2 did not protect cells. These data suggest that the coexistence of Na2SeO3 and HgCl2 was essential for the protective effects of Na2SeO3 against the toxicity of HgCl2 in Sp1K cells, and may involve selenium-mercury binding. This is supported by the results of an experiment in which earlier premixed mercury and selenium solutions were less cytotoxic than freshly mixed solutions. Furthermore, HgCl2 induced apoptosis in Sp1K cells, as revealed by nuclear specific dye (7-AAD) incorporation and cell flow cytometry, and this was prevented by the concurrent exposure to Na2SeO3. Inhibition of mercury-induced apoptosis in marine mammal cells, provided by selenium, may contribute to the in vivo protection. This study is the first report that addresses the mechanism of mercury-selenium antagonism in cultured cetacean cells at the cellular level.

Animals↗

Organic and inorganic forms of selenium inhibited differently fish (Rhamdia quelen) and rat (Rattus norvergicus albinus) delta-aminolevulinate dehydratase.

Selenium contamination in the aquatic environment can produce severe toxic effects to fish. The mammalian sulfhydryl-containing enzyme, delta-aminolevulinate dehydratase (delta-ALA-D), is inhibited after exposure to organic and inorganic forms of selenium. In the present study, the inhibitory effect of (PhSe)2, (BuSe)2, and Na2SeO3 on the activity of fish hepatic and gill delta-ALA-D was investigated and compared with the rat liver enzyme. Results indicated that delta-ALA-D activity varied considerably depending on the tissue, selenium form, and species considered. For fish (liver and gill), the IC50 values for delta-ALA-D inhibition by (PhSe)2, (BuSe)2, and Na2SeO3 were 274 and 76, 985 and 693, and 386 and 902 microM, respectively. For rat liver these values were 7, 10, and 5 microM, respectively. In contrast, fish and rat subcellular fractions similarly increased the oxidative effect of (PhSe)2 toward sulfhydryl groups from DTT. These catalytic properties of subcellular fractions from fish and rat liver were abolished by heat treatment. Taking into account that aquatic organisms can be in contact with higher concentrations of selenium for longer periods of time and accumulate more selenium than terrestrial animals, it is reasonable to suppose that fish delta-ALA-D can be a potential target for organic and inorganic selenium forms present in aquatic contaminated environments. From an ecotoxicological point of view, our results suggest a link between selenium-induced anemia signs in fish and the sensitivity of fish delta-ALA-D to selenium in natural habitats.

Animals↗

Selenised compressed salt blocks for selenium deficient sheep.

Salt blocks containing 30 or 120 ppm selenium were tested as the sole supplement for sheep farmed in a selenium-deficient area of New Zealand (Te Anau). Both concentrations were unsatisfactory in preventing selenium deficiency. In five trials using 120 ppm Se salt, the highest percentages of sheep found to be deficient were 31% (lambs) and 32% (ewes). If sheep which were classed as marginally deficient were included these percentages became 63% (lambs) and 56% (ewes). Some instances of selenium-responsive unthriftiness in lambs were encountered, and in one trial there was the possibility of selenium-responsive infertility having contributed to the low lambing performance of the ewes. There was no evidence of white muscle disease. Selenium levels in the liver and kidney were well below the permitted maximum. Because selenised salt failed to eliminate selenium deficiency, its use as a sole supplement for sheep grazing selenium deficient pasture is not recommended.

Journal Article↗

Selenium, vitamin E and polyunsaturated fatty acid concentrations in goat kids with and without nutritional myodegeneration.

Mean selenium and vitamin E (alpha-tocopherol) concentrations in the liver, myocardium and skeletal muscle of nine goat kids with nutritional myodegeneration (NMD) were significantly lower than those in a group of nine kids dying from other causes. Each of the 18 kids was from a different property in the southern half of the North Island. The polyunsaturated fatty acid composition of the liver, myocardium and skeletal muscle was not significantly different between the two groups, but the overall level of peroxidisable polyunsaturated fatty acids appeared high in both groups. A further 21 kids with confirmed NMD and live 'controls', submitted as routine cases to Palmerston North Animal Health Laboratory, were included with the above 18 kids in a comparison of liver selenium and alpha-tocopherol concentrations. Kids with NMD had liver selenium concentrations ranging from 170-1100 (mean = 380) nmol/kg and alpha-tocopherol from 0.7-11.0 (mean =2.2) micromol/kg. In control kids, the liver selenium concentration ranged from 530-4300 (mean = 1220) nmol/kg and a-tocopherol from 1.7-14.0 (mean = 5.6) pmollkg. Although these ranges overlapped, the results suggest that liver selenium concentrations <500 nmol/kg and alpha-tocopherol concentrations <2.5 micromol/kg should be regarded as deficient. Liver selenium concentrations from 500-1100 nmol/kg and alpha-tocopherol concentrations from 2.5-10 micromol/kg should be considered marginal. Goat kids appear to require more selenium than lambs or calves which may explain the higher prevalence of NMD in kids. In some cases, however, the disease is associated with low alpha-tocopherol suggesting that supplementation with selenium alone may not always be sufficient.

Journal Article↗

Alpha-tocopherol, selenium and polyunsaturated fatty acid concentrations in the serum and feed of spring-calving dairy heifers.

The objectives of this study were to provide baseline data for alpha-tocopherol, selenium and polyunsaturated fatty acid concentrations in the serum and feed of New Zealand dairy cattle, and to assess the likelihood that abnormal peroxide metabolism has a role in the impaired lactational and reproductive performance noted in selenium-deficient cattle. Twenty-four Friesian heifers were randomly allocated one of four winter diets consisting of hay with or without selenium supplementation, or pasture and silage with or without selenium supplementation. A winter diet consisting exclusively of hay (alpha-tocopherol concentration 19 mg/kg of dry matter) resulted in a pre-calving serum alpha-tocopherol concentration of 1.2 mg/l compared to 4.5 mg/l for pastured heifers (p<0.01). The pre-calving alpha-tocopherol concentration for the heifers fed hay fell into the range considered deficient (<2.0 mg/l), whereas heifers fed pasture and silage remained in the range considered adequate throughout the study period. Serum fatty acid concentration, and the proportion of fatty acids that were polyunsaturated, were lowest in the hay-fed heifers before calving (1.0 mg/ml, 37.1% respectively), and remained unchanged following re-introduction to pasture after calving in late July and August. Serum fatty acid concentration did not increase following the re-introduction of the heifers to pasture because of the unexpectedly low fatty acid concentration (4.8 g/kg of dry matter) of the mature winter pasture. In October, however, the proportion of fatty acids in serum that were polyunsaturated increased (50%) as did serum cy-tocopherol concentrations (greater than 13 mg/l). Mean serum selenium concentrations in the unsupplemented heifers ranged from 139 to 204 nmol/l, being lowest in October (p<0.01). Supplementation with intraruminal selenium pellets (two pellets delivering about 3 mg of selenium/day) increased serum selenium concentration and glutathione peroxidase activity (p<0.01) whereas the type of winter diet had no effect (p>0.05). These results suggest that dairy cattle wintered on hay can become Vitamin E-depleted, whereas the feeding of pasture and silage should provide adequate Vitamin E. The pasture offered following calving during July and August provided a low dietary polyunsaturated fatty acid challenge, suggesting that abnormal peroxide metabolism is unlikely to be an important mechanism in the impaired performance of selenium-deficient adult cattle which calve at this the of year.

Journal Article↗

A review of selenium deficiency in grazing ruminants. Part 2: towards a more rational approach to diagnosis and prevention.

ESTIMATING SELENIUM STATUS: Although the importance of selenium in ruminants has been recognised for over 30 years, problems associated with selenium deficiency are still frequently identified in grazing livestock operations. There is a growing diversity of tools available for the management of selenium deficiency giving rise to diagnostic and therapeutic dilemmas for the veterinary practitioner. There is no single test for selenium adequacy which can be considered superior in all diagnostic situations because the method of choice depends on the objective of the testing procedure. REFERENCE RANGES: Reviewing the available data, the current New Zealand reference ranges for selenium concentrations in ruminant tissue and feed appear valid. CLINICAL RELEVANCE: Management of selenium deficiency will continue to be important in grazing ruminants. Practising veterinarians should be familiar with the appropriate use of tests for selenium deficiency. Advice should be based on micronutrient analysis of animal tissue, defensible reference ranges backed by production response data, and supplementation programmes which optimise the return on investment.

Journal Article↗

Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling.

A previous controlled intervention trial showed that selenium supplementation was effective in reducing the incidence of prostate cancer. Physiological concentrations of selenium have also been reported to inhibit the growth of human prostate cancer cells in vitro. The present study describes the observation that selenium was able to significantly down-regulate the expression of prostate-specific antigen (PSA) transcript and protein within hours in the androgen-responsive LNCaP cells. Decreases in androgen receptor (AR) transcript and protein followed a similar dose and time response pattern upon exposure to selenium. The reduction of AR and PSA expression by selenium occurred well before any significant change in cell number. With the use of a luciferase reporter construct linked to either the PSA promoter or the androgen responsive element, it was found that selenium inhibited the trans-activating activity of AR in cells transfected with the wild-type AR expression vector. Selenium also suppressed the binding of AR to the androgen responsive element site, as evidenced by electrophoretic mobility shift assay of the AR-androgen responsive element complex. In view of the fact that PSA is a well-accepted prognostic indicator of prostate cancer, an important implication of this study is that a selenium intervention strategy aimed at toning down the amplitude of androgen signaling could be helpful in controlling morbidity of this disease.

Anticarcinogenic Agents↗

Bioassay of Selenium Sulfide (Gavage) for Possible Carcinogenicity (CAS No. 7446-34-6).

Selenium sulfide is an ingredient in dandruff shampoos used in concentrations of 1% in products sold over-the-counter and 2.5% in products which are available by prescription only. Prescription shampoos have been shown in clinical studies to be of therapeutic value against dandruff. An antimitotic mechanism of action is suggested by data showing that selenium sulfide decreases the rate of incorporation of radioactively labeled thymidine into the DNA of dermal epithelial cells. Approximately 200 kg of selenium sulfide is estimated to be used annually for this purpose. A bioassay of selenium sulfide for possible carcinogenicity was conducted by administering this substance by gavage to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered selenium sulfide suspended in 0.5% aqueous carboxymethylcellulose 7 days per week for 103 weeks at either 3 or 5 mg/kg/day for rats and 20 or 100 mg/kg/day for mice. As vehicle controls, groups of 50 rats and 50 mice of each sex were administered only the 0.5% aqueous carboxymethylcellulose. Similar groups of untreated controls also were used. All surviving rats and mice were killed and necropsied at week 104 or 105. The significant effects that could be related to administration of selenium sulfide at the doses used were decreased body weight and increased tumor formation in female mice and in rats of each sex. Dosed rats and female mice had an increased incidence of hepatocellular carcinomas and adenomas. Dosed female mice also had an increased incidence of alveolar/bronchiolar carcinomas and adenomas. Under the conditions of this bioassay, selenium sulfide was carcinogenic for F344 rats and female B6C3F1 mice, including hepatocellular carcinomas in male and female rats and female mice and alveolar/bronchiolar carcinomas and adenomas in female mice. Selenium sulfide was not carcinogenic for male mice; but they have been able to tolerate higher doses. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Negative Female Mice: Positive

Journal Article↗

Selenium compounds regulate p53 by common and distinctive mechanisms.

Selenium compounds show much promise in the prevention of prostate and other human cancers. Various selenium chemical forms have been shown to differ widely in their anticancer properties. The main dietary form is selenomethionine, which we showed modulated p53 activity by causing redox regulation of key p53 cysteine residues. In the current study we included other selenium chemical forms, sodium selenite and methyl-seleninic acid. All three forms are relevant selenium sources in human populations. All three forms can affect p53 activity defined as trans-activation of a p53-dependent reporter gene. In addition to the reduction of cysteine sulfhydryl groups, p53 phosphorylation was also affected in cells treated with selenium compounds. Methyl-seleninic acid caused phosphorylation of one or more p53 threonine residues, but did not affect any known serine phosphorylation sites. By contrast sodium selenite caused phosphorylation of p53 serines 20, 37 and 46 known to mediate apoptosis. Selenomethionine did not cause detectable phosphorylation of p53 serines or threonines. Our data show that, although p53 modulation may be a common denominator of selenium compounds, specific mechanisms of p53 activation differ among selenium chemical forms. Post-translational modifications of p53 are determinants of p53 activity and probably affect the threshold for p53-mediated functions. Different selenium chemical forms may differentially modify p53 for DNA repair or apoptosis in conjunction with a given level of endogenous or exogenous DNA damage.

Apoptosis↗

Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation.

Selenium has been associated with anticancer activity by affecting multiple cellular processes. We reasoned that the simultaneous modulation of multiple radioresponse regulators by selenium should increase radiosensitivity if selenium is combined with radiation in cancer therapy. Therefore, we explored the possibility of whether we could obtain an enhancement of radiosensitivity by the combination of selenium and ionizing radiation. We used two human lung cancer cell lines, NCI-H460 and H1299, as well as a human diploid lung fibroblast, WI-38, as the normal cell counterpart. The combined treatment of the cancer cell lines with Seleno-methionine and ionizing radiation resulted in increased cell killing as assessed by clonogenic survival assay whereas it had little effect on the normal diploid WI-38 cells. The increased radiosensitivity in the cancer cells was correlated with the attenuation of the key proteins involved in either cell survival signaling [Akt, EGFR (epidermal growth factor receptor), ErbB2 and Raf1] or DNA damage response (Mre11, Rad50, Nbs1, Ku80, 53BP1 and DNAPK). The attenuation of the proteins by the selenium compound was possibly caused by the effect on transcription and on protein stability since selenium treatment decreased both the RNA transcript and the protein stability of EGFR and DNAPK. By contrast, Seleno-L-methionine had no effect on the protein profile of a normal diploid fibroblast which is consistent with an intact radiosensitivity. These data provide possible clinical applications, as selenium selectively enhanced the radiosensitivity of the tumor cells whereas that of the normal cells was unaffected. Moreover, the selective decrease of cell proliferation signaling in tumor cells but not in normal cells should facilitate the repopulation of normal cells required for healing during radiation therapy. On the whole, the results suggest that the cancer preventive activity of selenium can be combined with ionizing radiation to improve the control of lung cancer.

Cell Line, Tumor↗

Removal of soluble selenium by a selenate-reducing bacterium Bacillus sp. SF-1.

In order to develop a biological process for removal of selenium from industrial wastewater, Bacillus sp. strain SF-1 was isolated from selenium-contaminated sediment. The bacterium reduces selenate to selenite and subsequently to nontoxic insoluble elemental selenium using lactate as an electron donor and selenate as an electron acceptor in an anaerobic condition. Elemental selenium transformed from soluble selenium was deposited both inside and outside of the cells. Since the selenate reduction rate of the strain SF-1 was higher than the selenite reduction rate, selenite was transiently accumulated. In an experiment of the repeated soluble selenium reduction by strain SF-1, 0.5 mM of selenate was sequentially treatable with a cycle of one day. Thus, our sequential system for removal of soluble selenium is very useful.

Bacillus↗

Zinc-selenium interaction in the rat.

Retention, dynamics of 75Se and 65Zn distribution, and elimination were studied in rats after separate or joint single doses of these metals. White female Wistar rats were divided into four groups (fifteen rats each). Group I received Na2(75)SeO3 (0.1 mg Se/kg i.g.), group II received Na2(75)SeO3 + ZnCl2 (5 mg Zn/kg s.c.), group III received 65ZnCl2, and group IV received 65ZnCl2 + Na2SeO3. The zinc and selenium contents in the tissues were estimated during 120 h after administration; excretion in urine and feces of animals was determined throughout the experiment. Combined administration of zinc and selenium resulted in an enhanced selenium retention in the brain, spleen, kidneys, blood, lungs, and heart. A selenium-induced increase in the concentration of zinc was noted in the bowels, blood, liver, kidneys, spleen, brain, and lungs. The effects of the zinc/selenium interaction were visible especially in the lowered level of excretion of these elements. Zinc induced a decrease in the excretion of selenium in urine, with no concomitant changes in the excretion in feces. However, a visible decrease in the excretion of zinc in the feces was observed in the presence of selenium. The present results indicate an occurrence of clear-cut interaction effects between zinc and selenium administered simultaneously in the rat.

Animals↗

Effect of selenium on the yield and quality of green tea leaves harvested in early spring.

Foliar applications of a fertilizer of selenite or selenate were carried out to determine the influence of selenium on the yield and quality of green tea leaves harvested in early spring. Numbers of sprouts and the yield were significantly increased by the application of selenium. The sweetness and aroma of green tea leaves were also significantly enhanced, and bitterness was significantly decreased by the application of selenium. However, no significant differences were found in sweetness, bitterness, and aroma between tea leaves fertilized with selenite and selenate. Se concentration was significantly increased by selenium fertilization, and tea enriched by sodium selenate had a significantly higher selenium content than did tea enriched by sodium selenite. Total amino acid and vitamin C contents were significantly enhanced by the application of selenium. Tea polyphenol contents were significantly decreased by fertilization with selenium. The marked difference of tea polyphenols was also found between applications of selenite and selenate.

Camellia sinensis↗

Nutritional selenium supplements: product types, quality, and safety.

Selenium supplements contain selenium in different chemical forms. In the majority of supplements, the selenium is present as selenomethionine. However, in multivitamin preparations, infant formulas, protein mixes, weight-loss products and animal feed, sodium selenite and sodium selenate are predominantly used. In some products, selenium is present in protein- or amino acid chelated forms; in still others, the form of selenium is not disclosed. Current evidence favors selenomethionine over the other forms of selenium. Extradietary supplementation of selenium at the dosage of 200 micrograms per day is generally considered safe and adequate for an adult of average weight subsisting on the typical American diet.

Anticarcinogenic Agents↗