SELENIUM

generic name: Selenium

Bibliography and References. Review.
List of selected scientific articles (abstracts). Experimental and clinical data.


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Biol Trace Elem Res. 2005 May;104(2):165-172.
Effect of Selenium on Expression of Selenoproteins in Mouse Fibrosarcoma Cells.
Reszka E, Gromadzinska J, Stanczyk M, Wasowicz W.
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.

Selenium (Se), an essential trace element, is incorporated into selenoproteins as selenocysteine using insertion machinery, including UGA codon and selenocysteine insertion sequence (SECIS) element in the 3'-untranslated region (3'-UTR) of mRNA. To assess the biological effects of tumor cells exposed to the elevated, but nontoxic Se level on glutathione peroxidase (GPx1 [cellular] and GPx3 [extracellular]), thioredoxin reductase (TrxR), and selenoprotein P (SeP) mRNA expression, we introduced a semiquantitative reverse transcription-polymerase chain reaction technique for each selenoprotein transcript using beta-actin as a reference housekeeping gene in mouse fibroblasts (WEHI 164). Cell lines were cultured with 1.0, 2.5, and 5.0 ng of Se in 1 mL of medium for 3 and 7 d, apart from the control cell line with standard medium. It was found that Se exerts a statistically significant (p<0.05) effect only on GPx3 mRNA, referred to as the optical density (OD) ratio (GPx3/β-actin). Moreover, the lowest Se level affected GPx3 mRNA expression more strongly than its highest concentrations. In an in vitro model applied in this study, GPx3 gene expression is most specific for Se supplementation.

Arch Environ Contam Toxicol. 2005 Apr 12;
Effects of Dietary Selenomethionine on Larval Rainbow Trout (Oncorhynchus mykiss).
Vidal D, Bay SM, Schlenk D.
Southern California Coastal Water Research Project, 7171 Fenwick Lane, Westminster, California, 92683, USA, daniel.schlenk@ucr.edu.

Increased selenium (Se) concentrations in water (>10 mug/L) have been measured in the San Diego Creek, which is a tributary of the Upper Newport Bay in Orange County, CA. The objective of this study was to develop tissue- and dietary-based thresholds for Se in resident fish species in San Diego Creek. A 90-day dietary experiment was conducted to determine the effects of seleno-L-methionine (SeMe) on the growth, survival, and whole-body Se accumulation in larval (24-day-old) rainbow trout. Decreased and oxidized glutathione (GSH-to-GSSG ratio) and thiobarbituric acid-reactive substances (TBARS) were also measured in livers of exposed animals to assess oxidative damage caused by Se. Fish food was spiked with SeMe to contain 4.6, 12, and 18 mug/g (dry weight) of Se. Fish exposed to SeMe for 90 days exhibited a significant decrease in body weight and fork length in the 4.6 and 12 mug/g Se treatments compared with controls. Whole-body total Se concentrations increased significantly in fish fed 12 and 18 mug/g SeMe after 90 days compared with controls. Lipid peroxidation (TBARS) and GSH-to-GSSG ratios were unchanged by SeMe treatment. Based on decreased growth after 90 days, a dietary Se lowest observed-effect concentration (LOEC) value of 4.6 mug/g and a Se body burden LOEC of 1.20 mug/g (wet weight) were estimated.

J Endocrinol. 2005 Mar;184(3):455-65.
Selenium and endocrine systems.
Beckett GJ, Arthur JR.
Clinical Biochemistry, University of Edinburgh, The Royal Infirmary of Edinburgh, 51 Little France Crescent, Little France, Edinburgh EH16 4SA, Scotland, UK.

The trace element selenium (Se) is capable of exerting multiple actions on endocrine systems by modifying the expression of at least 30 selenoproteins, many of which have clearly defined functions. Well-characterized selenoenzymes are the families of glutathione peroxidases (GPXs), thioredoxin reductases (TRs) and iodothyronine deiodinases (Ds). These selenoenzymes are capable of modifying cell function by acting as antioxidants and modifying redox status and thyroid hormone metabolism. Se is also involved in cell growth, apoptosis and modifying the action of cell signalling systems and transcription factors. During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage. Thyroidal D1 in rats and both D1 and D2 in humans are also up-regulated to increase the production of bioactive 3,5,3'-tri-iodothyronine (T3). In the basal state, GPX3 is secreted into the follicular lumen where it may down-regulate thyroid hormone synthesis by decreasing hydrogen peroxide concentrations. The deiodinases are present in most tissues and provide a mechanism whereby individual tissues may control their exposure to T3. Se is also able to modify the immune response in patients with autoimmune thyroiditis. Low sperm production and poor sperm quality are consistent features of Se-deficient animals. The pivotal link between Se, sperm quality and male fertility is GPX4 since the enzyme is essential to allow the production of the correct architecture of the midpiece of spermatozoa. Se also has insulin-mimetic properties, an effect that is probably brought about by stimulating the tyrosine kinases involved in the insulin signalling cascade. Furthermore, in the diabetic rat, Se not only restores glycaemic control but it also prevents or alleviates the adverse effects that diabetes has on cardiac, renal and platelet function.

J Anim Sci. 2005 Apr;83(4):852-7. Related Articles, Links
Comparison of dietary selenium fed to grower-finisher pigs from various regions of the United States on resulting tissue Se and loin mineral concentrations.
Mahan DC, Brendemuhl JH, Carter SD, Chiba LI, Crenshaw TD, Cromwell GL, Dove CR, Harper AF, Hill GM, Hollis GR, Kim SW, Lindemann MD, Maxwell CV, Miller PS, Nelssen JL, Richert BT, Southern LL, Stahly TS, Stein HH, van Heugten E, Yen JT.
North Central Regional Committee on Swine Nutrition (NCR-42) and Southern Regional Committee on Nutritional Systems for Swine to Increase Reproductive Efficiency (S-1012).

A study was conducted to evaluate the mineral content of pork tissue with particular emphasis on Se between various states (regions) having different diet (grain) indigenous Se concentrations. The study involved 19 states in the north, central, and southern regions of the United States, with committee members of NCR-42 and S-1012 (formerly S-288). A total of 62 pigs were used, with collaborators sending 100-g samples each of loin, heart, and liver, and a 3- to 4-g sample of hair (collected along the topline) from two to five market-weight pigs to a common laboratory for analysis. Diets at each station were formulated with locally purchased soybean meal and grain that was either grown or normally fed to pigs within their state. Tissues were analyzed for Se, but only the loin was analyzed for the macro- and micromineral elements. Correlation of dietary minerals to the tissue element was determined. The results demonstrated differences in tissue Se among states (P < 0.01), with high correlations of dietary Se to loin (r = 0.84; P < 0.01), heart (r = 0.84; P < 0.01), liver (r = 0.83; P < 0.01), and hair Se (r = 0.90; P < 0.01) concentrations. The correlation of hair Se to the Se concentration of loin, heart, and liver tissues was high (r > 0.90; P < 0.01). States in the west-central region of the United States and west of the Mississippi river had higher dietary Se and tissue Se concentrations than states in the eastern section of the Corn Belt, east of the Mississippi river, and along the East Coast. Generally, states did not differ greatly in their loin macro- and micromineral concentrations. The simple correlation of dietary minerals to their corresponding loin mineral concentration was generally non-significant, but most macrominerals had decreasing mineral concentrations when the dietary mineral level was higher. These results indicate that regional differences in tissue Se were influenced more by the indigenous Se content of the diet (grain) fed to the pigs than from sodium selenite.

Exp Parasitol. 2005 Apr;109(4):201-8.
Impact of vitamin E or selenium deficiency on nematode-induced alterations in murine intestinal function.
Au Yeung KJ, Smith A, Zhao A, Madden KB, Elfrey J, Sullivan C, Levander O, Urban JF, Shea-Donohue T.
Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC, USA.

The effects of deficiencies in the antioxidant nutrients, vitamin E and selenium, on the host response to gastrointestinal nematode infection are unknown. The aim of the study was to determine the effect of antioxidant deficiencies on nematode-induced alterations in intestinal function in mice. BALB/c mice were fed control diets or diets deficient in selenium or vitamin E and the response to a secondary challenge inoculation with Heligmosomoides polygyrus was determined. Egg and worm counts were assessed to determine host resistance. Sections of jejunum were mounted in Ussing chambers to measure changes in permeability, absorption, and secretion, or suspended in organ baths to determine smooth muscle contraction. Both selenium and vitamin E deficient diets reduced resistance to helminth infection. Vitamin E, but not selenium, deficiency prevented nematode-induced decreases in glucose absorption and hyper-contractility of smooth muscle. Thus, vitamin E status is an important factor in the physiological response to intestinal nematode infection and may contribute to antioxidant-dependent protective mechanisms in the small intestine.

 

Ann N Y Acad Sci. 2004 Dec;1031:234-41.
Selenium and vitamin e cancer prevention trial.
Klein EA.
Glickman Urological Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. kleine@ccf.org.

Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. In vitro evidence suggests that selenium and vitamin E work synergistically to cause cell-cycle arrest, induce caspase-mediated apoptosis, and act as antiandrogens in arresting clonal expansion of nascent tumors. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), sponsored by the National Cancer Institute, is an intergroup Phase III, randomized, double-blind, placebo-controlled, population-based clinical trial designed to test the efficacy of selenium and vitamin E alone and in combination in the prevention of prostate cancer. The study has a 2 x 2 factorial design with a target accrual of 32,400. Eligibility criteria include an age of at least 50 years for African Americans and of at least 55 years for Caucasians; a DRE not suspicious for cancer; a serum PSA no greater than 4 ng/mL; and a normal blood pressure. Randomization will be equally distributed among the four study arms, with intervention consisting of a daily oral dose of study supplement (200 mug l-selenomethionine or 400 mg of racemic alpha-tocopheryl) or matched placebo. Study duration is planned for 12 years, with a 5-year uniform accrual period and a minimum of 7 and maximum of 12 years of intervention. The primary endpoint for SELECT is the clinical incidence of prostate cancer as determined by a recommended routine clinical diagnostic work-up, including yearly DRE and serum PSA level. SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001, with final results anticipated in 2013.

J Nutr Sci Vitaminol (Tokyo). 2004 Oct;50(5):309-19.
Dietary habits and selenium intake of residents in mountain and coastal communities in Japan.
Miyazaki Y, Koyama H, Sasada Y, Satoh H, Nojiri M, Suzuki S.
Department of Public Health Nursing, Faculty of Nursing, Jobu University, Gunma 370-1393, Japan. miyazaki@jobu.ac.jp

We used a Simple Food Frequency Questionnaire (SFFQ) in combination with other dietary approaches to estimate the selenium intake from different food groups based on the average long-term diet, in two rural communities in Japan, one in a mountain area and the other in a coastal area. The intake frequencies of rice and wheat products were significantly different in the two districts. The intake frequencies of fish, meat, and eggs, which are rich in selenium, were not significantly different. The mean dietary selenium intake, estimated from the SFFQ and the 24-h recall method, was 82.7 microg/d (n=234) (range 19.2-180.1 microg/d) in the mountain community. The mean dietary selenium intake estimated from the SFFQ and average value of the normal portion size was 118.0 microg/d (n=123) (range 22.6-255.3 microg/d) in the coastal community. These estimated mean values exceeded the Japanese RDA, although the range of daily selenium intake was large. In the mountain community, fish made the largest contribution to dietary selenium intake (48.2% of daily total), followed by eggs (24.3%), and meat (17.0%). In the coastal community, fish accounted for 57.7% of daily total selenium intake, followed by meat (17.5%), and eggs (16.1%). In both districts, the total contribution of rice and wheat products was around 10%. It was found that the contribution of fish to dietary selenium intake was high and the contribution of cereals was low among Japanese.


Nutr Neurosci. 2002 Dec;5(6):363-74.
Selenium intake, mood and other aspects of psychological functioning.
Benton D.
Department of Psychology, University of Wales Swansea, Swansea SA2 8PP, Wales, UK.

Selenium is an essential trace element although the level of selenium in food items reflects the soil in which they were grown and thus varies markedly between different parts of the world. The metabolism of selenium by the brain differs from other organs in that at times of deficiency the brain retains selenium to a greater extent. The preferential retention of selenium in the brain suggests that it plays important functions. To date mood is the clearest example of an aspect of psychological functioning that is modified by selenium intake. Five studies have reported that a low selenium intake was associated with poorer mood. The underlying mechanism is unclear although a response to supplementation was found with doses greater than those needed to produce maximal activity of the selenoprotein glutathione peroxidase. Although the functions of many selenoproteins are unknown some play important roles in anti-oxidant mechanisms. As there are suggestions that oxidative injury plays a role in normal aging, schizophrenia, Parkinson's and Alzheimer's disease, the possible role of selenium is considered. Although there is evidence that supplementation with anti-oxidant vitamins shown some promise with Alzheimer's patients, and in preventing the development of tardive dyskinesia in schizophrenics taking neuroleptics, a role for selenium has been little considered.

J Urol. 2004 Feb; 171(2 Pt 1): 907-10.
Inorganic selenium retards progression of experimental hormone refractory prostate cancer.
Corcoran NM, Najdovska M, Costello AJ.
Department of Urology, Royal Melbourne Hospital, Victoria, Australia. Niall.

PURPOSE: The development of hormone refractory prostate cancer marks the onset of the terminal phase of the disease. Despite the use of traditional chemotherapeutic drugs as well as many novel agents life expectancy is not significantly increased beyond palliative care alone. Selenium is a micronutrient that is incorporated into a number of essential enzymes and a minimum intake is necessary for the maintenance of health. In the last few years evidence has accumulated from case-control and limited randomized control data that supranutritional doses of selenium could inhibit the progression of prostate cancer. While much attention has focused on its use as a chemopreventive agent, its use as specific therapy has been limited. We hypothesized that dietary supplementation of selenium would inhibit the progression of hormone refractory prostate cancer in an experimental model. MATERIALS AND METHODS: We established orthotopic PC3 tumors in the prostates of 6-week-old male nude mice and fed them a baseline selenium replete diet (0.07 ppm), supplementing intake with different forms of selenium (sodium selenate, selenomethionine, methylselenocysteine and selenized yeast) at 2 different concentrations (0.3 and 3 ppm) in drinking water. RESULTS: Inorganic selenium (sodium selenate) significantly retarded the growth of primary prostatic tumors and the development of retroperitoneal lymph node metastases, which was associated with a decrease in angiogenesis. CONCLUSIONS: High dose dietary supplementation of inorganic selenium inhibits the progression of hormone refractory prostate cancer, which is due at least in part to a decrease in angiogenesis.

Nutr Neurosci. 2002 Dec;5(6):363-74.
Selenium intake, mood and other aspects of psychological functioning.
Benton D.
Department of Psychology, University of Wales Swansea, Swansea SA2 8PP, Wales, UK.

Selenium is an essential trace element although the level of selenium in food items reflects the soil in which they were grown and thus varies markedly between different parts of the world. The metabolism of selenium by the brain differs from other organs in that at times of deficiency the brain retains selenium to a greater extent. The preferential retention of selenium in the brain suggests that it plays important functions. To date mood is the clearest example of an aspect of psychological functioning that is modified by selenium intake. Five studies have reported that a low selenium intake was associated with poorer mood. The underlying mechanism is unclear although a response to supplementation was found with doses greater than those needed to produce maximal activity of the selenoprotein glutathione peroxidase. Although the functions of many selenoproteins are unknown some play important roles in anti-oxidant mechanisms. As there are suggestions that oxidative injury plays a role in normal aging, schizophrenia, Parkinson's and Alzheimer's disease, the possible role of selenium is considered. Although there is evidence that supplementation with anti-oxidant vitamins shown some promise with Alzheimer's patients, and in preventing the development of tardive dyskinesia in schizophrenics taking neuroleptics, a role for selenium has been little considered.

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