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Selenate fortification improves selenium status of term infants fed soy formula.

Thirty-three healthy term infants were fed either soy formula (SF, 0.028 mumol Se/L; n = 17) or soy formula with added selenate (SF+Se, 0.17 mumol Se/L; n = 16) from birth (+4 d) to 16 wk. Selenium intakes of infants fed SF+Se were similar to the recommended dietary allowance and significantly greater than those of SF-fed infants. The SF group had significantly lower plasma, erythrocyte, and urine selenium, and lower plasma and erythrocyte glutathione peroxidase (GPx) activities at 16 wk compared to those of infants fed SF+Se. A decrease in plasma selenium was observed in SF-fed infants, whereas no differences in plasma selenium were found in infants fed SF+Se. These results indicate that selenate added to soy formula is highly available and effective at maintaining infant plasma and erythrocyte selenium concentrations and GPx activities that are greater than those of infants fed soy formula not fortified with selenium.

Double-Blind Method↗

The chemical form of selenium influences 3,2'-dimethyl-4-aminobiphenyl-DNA adduct formation in rat colon.

There is increasing evidence that selenium can protect against tumorigenesis or preneoplastic lesion development induced by chemical carcinogens. This study examined whether selenite, selenate or selenomethionine would be protective against 3, 2'-dimethyl-4-aminobiphenyl (DMABP)-DNA adduct formation in the liver and colon of rats and sought to delineate the mechanism for the protective effects of the different chemical forms of selenium against aberrant crypt formation, a preneoplastic lesion for colon cancer. After injection of DMABP, two DNA adducts were identified in the liver and colon of rats. Supplementation with either 0.1 or 2.0 mg selenium/kg diet as either selenite or selenate but not selenomethionine resulted in significantly fewer (53-70%; P < 0.05) N-(deoxyguanosin-8-yl)-(deoxyguanosin-8-yl)-3, 2'-dimethyl-4-aminobiphenyl (C8-DMABP)-DNA adducts in the colon but not the liver than in rats fed a selenium-deficient diet. Rats supplemented with selenomethionine had greater (P < 0.05) plasma and liver selenium concentrations and glutathione peroxidase activity than those supplemented with selenite or selenate; however, they also had more DMABP-DNA adducts. The protective effect of selenite and selenate against DMABP-DNA adduct formation apparently is not a result of alterations in plasma or liver selenium concentrations or altered glutathione peroxidase or glutathione transferase activities but may be related to differences in the metabolism of the different forms of selenium.

Aminobiphenyl Compounds↗

Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS.

The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of macaques could be used as a model system to assess the role of selenium in AIDS. Plasma and serum selenium levels were determined by standard assays in monkeys before and after inoculation of SIV. SIV-infected cells or cells expressing the HIV Tat protein were labeled with 75Se, and protein extracts were prepared and electrophoresed to analyze selenoprotein expression. Total tRNA was isolated from CEMx174 cells infected with SIV or from KK1 cells infected with HIV, and selenocysteine tRNA isoforms were characterized by reverse phase chromatography. SIV-infected monkeys show a decrease in blood selenium levels similar to that observed in AIDS with development of SAIDS. Cells infected with SIV in vitro exhibit reduced selenoprotein levels and an accumulation of small molecular weight selenium compounds relative to uninfected cells. Examination of the selenocysteine tRNA isoforms in HIV-infected KK1 cells or SIV-infected CEMx174 cells reveals an isoform distribution characteristic of selenium-deficient cells. Furthermore, transfection of Jurkat E6 cells with the Tat gene selectively altered selenoprotein synthesis, with GPX4 and Sep15 being the most inhibited and TR1 the most enhanced. Taken together, the data show that monkeys infected with SIV in vivo and cells infected with SIV in vitro will provide appropriate models for investigating the mechanism(s) responsible for reduced selenium levels that accompany the progression of AIDS in HIV disease.

Acquired Immunodeficiency Syndrome↗

Isolation and partial characterization of selenium-containing tRNA from germinating barley.

Selenium-containing tRNA was discovered in germinating barley for the first time with the 75Se isotopic tracer technique; therefore, this technique was used to study the effect of different concentrations of selenium and sulfur in the medium on the content of selenium-containing tRNA in germinating barley. Se-containing tRNAs and its hydrolysates were isolated, purified, and characterized by means of column chromatography, ion-exchange chromatography, high-performance liquid chromatography, and the ultraviolet-visible spectrum. The results show that the amount of selenium in tRNA is almost unaffected by the sulfuric content in the medium, and the pathway for selenium and sulfur to enter tRNA might not be exactly the same. Selenium exists within tRNA in the form of 5-methylamine methyl-2-selenouridine, just as it does within a microorganism tRNA.

Chromatography, Ion Exchange↗

[Effects of selenium dioxide on regulatory regions P250 of c-fos gene].

BACKGROUND & OBJECTIVE: This study was designed to investigate the impact of selenium dioxide (SeO2) on regulatory regions P250 of c-fos gene and to seek possible regulation mechanism. METHODS: HeLa cells were transfected with plasmids containing upstream regulating regions of c-fos chloramphenicol acetyl-transferase (CAT). The cells were cultured in various concentration of selenium dioxide. CAT expression in transfected cells was observed. RESULTS: After transfected HeLa cells were exposed to selenium dioxide, CAT expression showed obvious increase, especially in 10 micromol/L and 30 micromol/L selenium dioxide group (P< 0.05). CONCLUSION: Trough affecting regulatory regions P250 of c-fos gene, Selenium dioxide plays biological effect of regulating tumor cells. Selenium dioxide possibly has anti-tumor effects.

Chloramphenicol O-Acetyltransferase↗

[Speciation analysis of selenium by flow-injection catalytic spectrophotometry].

A new flow-injection catalytic spectrophotometric method was proposed for the determination of Se(IV) based on its catalytic effect on the reduction reaction of azure I by Na2S in pH 7.0 citric-acid sodium-hydrogen-phosphate buffer solution. Some different schematic diagrams of FIA were compared. Effects of the flow rates of reagents and sample, the medium and its acidity, the temperature, and coexistent substances were studied respectively. The amount of used reagents and the experimental conditions for sampling volume and coil length were optimized by using the controlled and weighed centroid simplex method. The Linear range of the determination is 0.1-2.0 mg x L(-1), the detection limit is 0.015 mg x L(-1), the relative standard deviation is less than 3.1%, and the sampling frequency is 120 samples per hour. The method has been applied to the determination of organic selenium and inorganic selenium in garlic and selenium-yeast. It was found that garlic had a strong enriching effect for selenium, and the conversion ratio of organic selenium decreased with increasing the concentration of selenium in the environment. The recovery of this method is 97.1%-104.3%.

Catalysis↗

[Protection from anoxic myocardial injury in fetal mouse heart culture by selenium].

Fetal hearts taken from the 17 day pregnant mice were cultured in minimum essential medium (MEM) + 0.5 ug ml of Na2SeO, and in MEM alone with oxygen for 24 h, and then the hearts in groups were exposed to 15, 20, 30, 40 min, 1 h, 3h and long term of anoxia respectively. The results showed that the survival and beating of the cultured fetal mouse hearts with anoxia were prolonged by selenium. Using lanthanum as a marker, we found that after 20 min of anoxia, this electroopaque marker remained extracellular in the selenium-treated hearts, however, intracellular lanthanum could be found in the control hearts, entering selectively into the swelling mitochondria. During the same period of anoxia, ACPase reaction products could be only found in the lysosomes and in the Golgi complex in the selenium-treated hearts, but a lot of reaction products deposited in cytoplasm in the control hearts. By electron microscopy, at 40 min of anoxia, there were swelling of mitochondria, with cristae partially lost and plasma-membrane changed and so on. Generally normal ultrastructure was observed in the selenium-treated hearts at 40 min of anoxia. The cytoplasm was rich in ribosomes and the sarcoplasmic reticulum with a rough face. There events showed that cellular membrane and membrane-bound organelles appeared to be well protected target by the selenium. Therefore, selenium may play an important role in the synthesis of protein.

Animals↗

Selenium and signal transduction: roads to cell death and anti-tumour activity.

Accumulated evidence from prospective studies, intervention trials and studies on animal models of cancer have suggested a strong inverse correlation between selenium intake and cancer incidence. Several putative mechanisms have been suggested to mediate the chemopreventive activities of selenium: of these, the inhibition of cellular proliferation and the induction of apoptosis are particularly attractive. The mitogen activated protein kinase (MAPK) pathways are known to be important regulators of cell death and our recent work has focused on the involvement of these pathways in selenium-induced apoptosis in primary cultures of oral cancers and corresponding normal mucosa derived from biopsy material. Using this system, the oral carcinoma cells were found to have enhanced sensitivity to apoptosis when treated with certain selenium compounds compared to normal oral mucosa. Induction of Fas ligand was associated with selenium-induced apoptosis. Signal transduction studies suggests that selenium induces several changes in the MAPK signalling pathways but functional intervention/inhibitor studies indicate that activation of the JNK pathway seems to be most important.

Animals↗

Modulation of steroidogenesis by selenium in a novel adrenal cell line developed using targeted tumorigenesis.

UNLABELLED: Glutathione peroxidase (GPx-1) is a selenoenzyme that metabolizes H(2)O(2), a source of potentially toxic free radicals. Steroidogenesis is markedly inhibited by H(2)O(2) in vitro. OBJECTIVE: to study the effects of selenium deficiency on GPx activity and adrenal steroidogenesis in a novel adrenal cell line developed using targeted tumorigenesis. METHODS: AN4Rppc7 cells were grown for 7 days in serum-free medium. 8-Br-cAMP-stimulated concentrations of steroid hormones were measured by RIA. StAR (Steroid Acute Reactive Protein) mRNA was measured by Northern blot. RESULTS: selenium deficiency caused a 99% There was a 51%, progesterone, corticosterone and aldosterone production, respectively (p<0.05 by ANOVA). StAR mRNA was not affected by selenium. CONCLUSIONS: selenium deficiency causes a marked decrease in GPx activity. Decreased steroid hormone production occurs for selenium concentrations equal or lower than 5 nM. The absence of changes in StAR mRNA content suggests that selenium deficiency does not affect cholesterol access to the mitochondria.

8-Bromo Cyclic Adenosine Monophosphate↗

Effects of dietary selenium on hepatic and renal tumorigenesis induced in rats by diethylnitrosamine.

Seven groups of female Sprague-Dawley rats (approximately 200 gm initial body weight) were injected i.p. with a single subcarcinogenic dose of diethylnitrosamine (40 mg per kg body weight) between 8 to 10 hr after partial hepatectomy, and after a recovery period of 3 weeks (herein called induction stage) received 0.05% phenobarbital in the diet for the rest of the experiment (promotion stage). The rats were fed a 20% casein-based diet containing 0.16 ppm of selenium or the same diet supplemented with 4 or 6 ppm of selenium as sodium selenite. The effects of these three dietary regimens were tested when administered 9 to 11 days before and during induction, 1 week before and during promotion or during the entire experiment. Pair-feeding conditions were used to minimize influences due to differences in food intake and growth. Despite similarities in food intakes, the growth rates in groups receiving the 6 ppm-selenium diet during promotion or during the entire experiment were in general significantly lower than in rats fed the 4 ppm-selenium diet or the 0.16 ppm-selenium basal diet. Survival rates were also significantly reduced in rats fed the 4 and 6 ppm-selenium diets during promotion or during the entire experiment. In rats killed at the 19th week for interim assessment of the experiment's progress, the stereologically analyzed numerical and volumetric densities of hepatic premalignant hyperplastic nodules did not differ significantly between groups. All the remaining rats were killed at the 46th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial.

Selenium status has been inversely associated with colorectal cancers (CRC) and adenomas. This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow-up. Of the 1,312 randomized to 200 mcg of selenized yeast of matching placebo, 598 participants underwent endoscopic screening (flexible sigmoidoscopy or colonoscopy) for CRC sometime during the follow-up period, which ended in February 1, 1996. There was no colorectal screening performed at baseline. Of those screened, 77% were male (with a mean age of 62.8 years), 42% were former and 25% were current smokers. Adenomas were classified as prevalent (identified at the first endoscopic examination post-randomization during the follow-up period) or incident (identified at the second or subsequent examination). Ninety-nine prevalent and 61 incident adenomas were ascertained. Logistic regression odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender and smoking status. For prevalent adenomas, there was a suggestive but nonsignificant decrease in risk associated with selenium treatment (OR = 0.67, 95% CI = 0.43-1.05). Subjects in the lowest tertile of baseline selenium (OR = 0.27, 95% CI = 0.09-0.77) and current smokers (OR = 0.27, 95% CI = 0.11-0.66) had significant reductions in risk. The OR for incident adenomas was 0.98 (95% CI = 0.57-1.68). In addition to being associated with a reduced risk of incident CRC, selenium supplementation was associated with a significantly reduced risk of prevalent adenomas, but only among subjects with either a low baseline selenium level or among current smokers.

Adenoma↗

Serum vitamin E, serum selenium and the risk of gastrointestinal cancer.

The association between levels of alpha-tocopherol and selenium in serum and subsequent risk of gastrointestinal cancer was investigated in a longitudinal study based on 36,265 Finnish men and women, aged 15-99 and initially free of cancer. Serum alpha-tocopherol and serum selenium levels at entry into the study were measured from stored serum samples of 150 incident gastrointestinal cancer cases diagnosed during a follow-up of 6-10 years and for 276 controls who were matched for sex, age and place of residence. Subjects with a low level of alpha-tocopherol or selenium had an elevated subsequent risk of cancer of the upper gastrointestinal tract. This association persisted among men after adjustment for various confounding factors and after the exclusion of those with cancer diagnosed during the first 2 years of follow-up. The relative risk of cancer of the upper gastrointestinal tract among men who fell in the lowest quintile of serum selenium was 3.3 (95% confidence limits, 1.3 and 9.1) while among those who fell in the 3 lowest quintiles of alpha-tocopherol it was 2.2 (95% confidence limits 0.9 and 5.6) compared with those in the higher quintiles. Serum levels of selenium or alpha-tocopherol in general were not inversely associated with colorectal cancer risk. These findings indicate that high selenium intake and possibly also high vitamin E intake, especially among men, may provide protection against cancer of the upper gastrointestinal tract but not against colorectal cancer.

Aged↗

A case-control study of oral cancer and pre-diagnostic concentrations of selenium and zinc in nail tissue.

A case-control study of oral cancer was conducted in western Washington state between 1983 and 1987. Cases (n = 379) were identified through a population-based registry, and controls (n = 514) were selected by telephone using random digit dialing. Subjects participated in a personal interview, completed a food-frequency questionnaire, and submitted clippings from the nails of each great toe for the determination of selenium and zinc concentrations. The odds ratio (OR) for low selenium levels in nail tissue (lowest 25% of the distribution compared to the upper 75%) was 1.4 (95% confidence interval (CI) 1.0-2.2). Likewise, the odds ratio for low zinc levels in nails was 1.6 (95% CI 1.0-2.3), but for low dietary zinc was 1.0 (95% CI 0.7-1.7). Men with oral cancer had lower nail selenium levels than did the controls (OR = 1.9), but women with oral cancer did not (OR = 0.6). Individuals 20 to 39 years of age with oral cancer, in particular, were more likely to have lower selenium levels in nail tissue than controls (OR = 16.4). There was a significant interaction between selenium and ascorbic acid levels which could not be explained by cigarette use. Subjects at greatest risk had low levels of both nutrients (OR = 3.8 for smokers and OR = 5.7 for non-smokers). However, since the elements were deposited in the nail matrix close to the date of diagnosis, the differences in the element concentrations between cases and controls may have been a result of the disease. Further etiologic studies of selenium, vitamin intake and oral carcinoma are warranted.

Adult↗

Effects of selenium in vitro on human T-lymphocyte functions and K-562 tumor cell growth.

In vitro E-rosette formation, lymphocyte mitogenesis, and natural killer (NK) cell activity of human blood lymphocytes were strongly inhibited by high concentrations (10(-4) M) of sodium selenite, sodium selenate, and selenium dioxide. Lower concentrations (10(-5) or 10(-7) M) also inhibited E-rosette formation and natural killer cell activity against K-562 tumor cells. Lymphocyte transformation induced by concanavalin A (con A) or pokeweed mitogen (PWM) was also inhibited by all selenium compounds tested, but only at the highest concentrations (10(-5) and 10(-4) M). There was depression of the total number of viable lymphocytes following incubation with selenium dioxide only at a high concentration (10(-4) M). Interferon production was enhanced at lower levels (10(-9) to 10(-6)M) of selenium dioxide while a higher concentration (10(-5) and 10(-4)M) appeared to inhibit its production. The mechanism of inhibition by selenium compounds (10(-4) M) is due, in part, to the decrease of viable lymphocytes. It is unclear how other and lower concentrations (10(-7) or 10(-9) M) of selenium compounds inhibit E-rosette formation, NK activity, or K-562 tumor cell growth.

Adult↗

Thioredoxin reductase activity is decreased by selenium deficiency.

Animal thioredoxin reductase is a selenoprotein. In this study, thioredoxin reductase activities in liver, kidney, and brain have been compared in rats fed selenium-deficient and control diets for 14 weeks following weaning. Selenium deficiency caused a decrease in thioredoxin reductase activity from control to 4.5% in liver and 11% in kidney. However, brain thioredoxin reductase activity was not affected by selenium deficiency of this severity. Gold inhibited thioredoxin reductase activity in the liver in a manner typical of its effect on selenoenzymes. Repletion of selenium-deficient rats with injections of selenium caused thioredoxin reductase activity to increase more rapidly in the liver than glutathione peroxidase activity but more slowly than selenoprotein P. These results indicate that thioredoxin reductase activity in liver and kidney is sensitive to selenium nutritional status but that brain thioredoxin reductase activity is less sensitive.

Animals↗

Evaluation of the hazard quotient method for risk assessment of selenium.

Environmental contamination with selenium from industrial and agricultural sources has poisoned fish and wildlife at several locations in the United States. Monitoring and risk assessment activities are currently being conducted by many state and Federal agencies. The U.S. Environmental Protection Agency (EPA) recommends a hazard quotient (HQ) method (waterborne concentration divided by the national water quality criterion) to assess the toxic threat of individual waterborne elements, including selenium. An evaluation of the EPA HQ method was conducted by comparing it to a recently published protocol (Protocol) for selenium assessment. Hazard estimates obtained using HQ were found to be invalid because the EPA water quality criterion is outdated, and the procedure uses mean rather than maximum waterborne concentrations. The HQ method seriously underestimates hazard and could lead to risk management decisions that would not protect fish and wildlife from selenium toxicity. The Protocol method provides an accurate assessment because it evaluates hazard by examining multiple exposure pathways on a site-specific basis. Until a revised (lowered) national water quality criterion is available, the EPA HQ method should not be used for selenium. Even then, with the availability of the Protocol, HQ analysis should be restricted to data sets where water is the primary or sole source of information on environmental concentrations of selenium.

Environmental Monitoring↗

Environmental hazard of selenium in the Animals La Plata water development project.

A hazard assessment of selenium was conducted for the Animas La Plata Project, a multiple-use water development proposed for Colorado and New Mexico by the United States Bureau of Reclamation. A published protocol for aquatic hazard assessment of selenium was applied to environmental monitoring data to assess current threats to biota in the water supply rivers (Animas, La Plata, and Mancos Rivers). Hazard evaluation were also made for two proposed reservoirs (Ridges Basin and Southern Ute Reservoirs) based on estimated concentrations of selenium. The assessment protocol indicated moderate hazard in the Animas and La Plata Rivers, and high hazard in the Mancos River and both of the proposed reservoirs. These ratings indicate that the risk of selenium poisoning in fish and aquatic birds is substantial. Moreover, the geology and climate of this site make it prone to irrigation-induced selenium contamination of water and biota. The water supplies already contain dangerously high concentrations of selenium that may increase further due to agricultural irrigation drainage. The stage is set for significant environmental problems unless a development scenario can be devised that will effectively reduce ecological risks.

Animals↗

A teratogenic deformity index for evaluating impacts of selenium on fish populations.

This paper describes a method for using teratogenic deformities in fish as the basis for evaluating impacts of selenium contamination. Teratogenic deformities are reliable bioindicators of selenium toxicosis in fish. They are produced in response to dietary exposure of parent fish and subsequent deposition of selenium in eggs. There is a close parallel between selenium concentrations in eggs, incidence of teratogenic deformities in larvae, and magnitude of reproductive failure. Using these relationships, an index was developed for teratogenic-based assessment of impacts to fish populations. The index is composed of three ratings that signify increasing levels of terata-induced population mortality: 1, negligible impact (< 5% population mortality); 2, slight to moderate impact (5-20% population mortality); 3, major impact (> 20% population mortality). Each rating is based on the anticipated population-level impact of the corresponding degree of mortality. Teratogenic-based impact assessment provides a conclusive cause-effect linkage between the contaminant and the fish. It is particularly useful for verifying selenium-induced impacts on reproductive success because poor reproduction can be caused by many things-i.e., fluctuating water levels, nest predation, food shortages, poor recruitment, etc. The index given here should be a useful tool for evaluating the effect of selenium on fish populations. Moreover, application of this technique may save considerable time and money by identifying the most efficient use of manpower and funds early in the assessment process.

Abnormalities, Drug-Induced↗