SEARCH · PubMed Health

Results for “Selenium Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1996

The inhibition of radiation-induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065.

In order to evaluate the anti-mutagenic effects of the potential chemoprotective compounds selenium and (S)-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-1065), CHO AA8 cells were exposed to both compounds either individually or in combination prior to irradiation. Mutation frequency following exposure to 8 Gy was evaluated by quantitation of the mutations detected at the hprt locus of these cells. Protection against radiation-induced mutation was observed for both 30 nM sodium selenite or 4 mM WR-1065. In addition, the protection against mutation induction provided by the combination of these agents appeared additive. In contrast, sodium selenite did not provide protection against radiation toxicity when provided either alone or in conjunction with WR-1065. In order to evaluate the possible mechanisms of the anti-mutagenic effects observed in these cells, glutathione peroxidase (GPx) activity was evaluated following exposure to the chemopreventative compounds. The addition of sodium selenite to the culture media resulted in a 5-fold increase in GPx activity, which was unaltered by the presence of the WR-1065. Northern analysis of RNA derived from these cells indicated that selenium supplementation resulted in a marginal increase in the mRNA for the cytosolic GPx (GSHPx-1) which was insufficient to account for the stimulation of GPx activity observed in cellular extracts. These results suggest that selenium and WR-1065 offer protection via independent mechanisms and that GPx stimulation remains a possible mechanism of the anti-mutagenic effect of selenium.

Animals↗

PubMed1972

Dimethylselenide and dimethyltelluride formation by a strain of Penicillium.

A strain of Penicillium which produced dimethylselenide from inorganic selenium compounds was isolated from raw sewage. Sulfate and methionine enhanced growth of the fungus and its production of dimethylselenide in media containing selenite. In solutions containing selenate, methionine inhibited dimethylselenide formation while stimulating proliferation of the fungus. Dimethylselenide was also generated from inorganic selenide. Alkylation did not appear to be a significant mechanism of selenium detoxication by this organism. Dimethyltelluride was also produced by the organism from several tellurium compounds, but this product was synthesized only in the presence of both tellurium and selenium. The yields of dimethylselenide and dimethyltelluride varied with the relative concentrations of selenium and tellurium in the medium.

Alkylation↗

PubMed1987

Periodate-oxidized adenosine inhibits the formation of dimethylselenide and trimethylselenonium ion in mice treated with selenite.

The metabolic detoxification of selenite and many other selenium compounds involves a series of S-adenosylmethionine-dependent methylations yielding dimethylselenide (DMSe), which is exhaled, and trimethylselenonium ion (TMSe), which is excreted in the urine. This paper shows that periodate-oxidized adenosine (Adox) inhibits these methylation reactions in vivo and increases the toxicity of selenite. When Adox was injected in mice at 100 mumol/kg 30 min before injection of [75Se]selenite at 0.4 mg Se/kg the appearances of [75Se]DMSe in the breath and [75Se]TMSe in the liver were completely inhibited for 90 min. This was mediated by accumulation of S-adenosylhomocysteine, the methyltransferase inhibitor, in the livers of Adox-treated mice due to inhibition of its hydrolase enzyme. During 24 h, Adox-treated mice excreted no detectable urinary [75Se]TMSe and exhaled only 20% as much [75Se]DMSe as controls. The urine of Adox-treated mice also contained S-adenosylhomocysteine at a level (ca. 4 mM), 200 times that of untreated mice, which provided a convenient index of methylation potential in the intact animal. When three groups of three mice each were injected with 100 mumol Adox/kg, selenite at 4 mg Se/kg, or a combination of the two, the mice receiving the combination were dead within 2 days, while the mice in the other two groups all survived at least 4 days. These results verify the enzymatic nature of selenium methylation in vivo, support its importance in detoxification, and indicate the value of Adox in further studies of selenium metabolism.

Adenosine↗

PubMed1985

Selenium deficiency in cultured adrenocortical cells: restoration of glutathione peroxidase and resistance to hydroperoxides on addition of selenium.

Cultured bovine adrenocortical cells were previously shown to be functionally deficient in selenium and vitamin E when grown in medium supplemented with fetal bovine serum. In the present experiments, the lack of significant bioavailable amounts of selenium in the medium was demonstrated by the finding of only low levels of glutathione peroxidase in the cultured cells (0.008 U/mg protein compared with 0.045 U/mg protein in fresh adrenocortical tissue). When 20 nM selenium as selenite was added to the cultured adrenocortical cells, glutathione peroxidase activity increased continuously over 72 h, with a total increase of about eightfold over this period. Over the same time-course, the highest concentration of cumene hydroperoxide tolerated by the cells without cell death increased progressively from 10 microM to 50 microM. Addition of 1 microM alpha-tocopherol also increased the amount of cumene hydroperoxide tolerated to 50 microM. Cell death was measured by cloning efficiency after removal of cumene hydroperoxide. Addition of either selenium or alpha-tocopherol had little effect on the growth rate of the cells over six passages, even when residual vitamin E was removed from the serum by extraction with ether and residual low molecular weight selenium compounds were removed by dialysis. It is concluded that combined deficiency of selenium and vitamin E, at least in the presence of other components of fetal bovine serum, has little effect on the ability of the cells to survive under normal conditions, as evidenced by continued long-term proliferation. However, the low levels of glutathione peroxidase resulting from selenium deficiency cause an increase susceptibility to peroxide-mediated toxicity. The combined deficiency of selenium and vitamin E impairs the ability of cells to survive under adverse conditions, as well as altering mitochondrial functions, as previously demonstrated.

Adrenal Cortex↗

PubMed1984

Plasma selenium concentration in healthy Japanese children and adults determined by flameless atomic absorption spectrophotometry.

This study showed a rapid and direct method for determining selenium concentration in plasma by flameless atomic absorption spectrophotometry, and differences in plasma selenium concentration in healthy children and adults. A direct method is possible, since selenium is heat stable in the presence of nickel. With this method, the recovery of selenium added to plasma was 100.3 +/- 5.7%, and the relative standard deviation in repeated determinations of pooled plasma selenium was 3.0% and 6.8%. The plasma selenium concentration in adults was 99.4 +/- 12.5 ng/ml, lower than reported concentrations from the United States and Canada, and higher than those from New Zealand. These variations may reflect dietary habits, bioavailability of selenium compounds in diet, racial difference, or different analytical methods. The mean concentration of plasma selenium at 1 to 6 months of age (51.0 +/- 13.1 ng/ml) was significantly lower than in adults (p less than 0.001); it increased gradually and steadily to the adult level with age. This age-related difference of plasma selenium level is similar to that reported previously.

Adolescent↗

PubMed1987

Ebselen: a new approach to the inhibition of peroxide-dependent inflammation.

Ebselen is a novel organo-selenium compound which catalytically inactivates peroxides in vitro in a manner similar to that of glutathione peroxidase (GSH-Px). In addition, ebselen also inactivates leukotriene B4 (LTB4) generated by pig leukocytes in vitro by isomerizing this eicosanoid to its biologically inactive 6-trans isomer. In vivo, ebselen is a weak oral inhibitor of carrageenan paw oedema and adjuvant arthritis in the rat, differentiating it from classical NSAIDs such as indomethacin and diclofenac. In contrast, oral ebselen, like (intra-articular) catalase, is an effective inhibitor of monoarthritis induced in mice with amidated glucose oxidase (aGO) and dose-dependently inhibits cobra-venom-factor-induced paw oedema in rats. Indomethacin and piroxicam are weakly active or ineffective in these models. The data indicate that ebselen is likely to be useful in the therapy of inflammatory conditions in which reactive oxygen species, such as peroxides, play an aetiological role.

Animals↗

PubMed1998

Lessons from basic research in selenium and cancer prevention.

The article reviews the progress in basic research of selenium and cancer prevention during the past decade. Special emphasis is placed on the following four major areas of discussion: 1) chemical forms of selenium and anticarcinogenic activity; 2) selenium-enriched food; 3) in vitro effects of selenite vs. monomethylated selenium; and 4) aromatic selenium compounds. It is clear that basic research has contributed new knowledge to our understanding of selenium biochemistry, anticancer efficacy and regulation of cell growth. Some of this information could be ready for incorporation into the design of a second-generation selenium trial in humans.

Anticarcinogenic Agents↗

PubMed1979

[Selective fixation of methylselenobenzoic acid by the pineal gland].

Investigation of the localization in the central nervous system of the rat of an epileptogenic agent, methylseleno-2-benzoic acid, did not lead to its selective distribution in the cerebral cortex or in the brainstem in relation with its biological activity. But a systematic study of the distribution of this compound labelled with 75Se at a high specific activity has revealed a rate of fixation by the pineal gland 4 to 5 times higher than that of other tissues of the central nervous system. After a survival time of 4 hours, the radioactivity of the pineal gland exceeds that of the blood. A parallel study of the distribution of the 75SeO3- ion on the one hand of the 35S homolog of the 75Se compound on the other hand has demonstrated that the fixation by the pineal gland is bound to the molecular structure of the selenium compound.

Animals↗

PubMed1980

[Dynamics of selenium in the blood serum of sows after a supplementary feeding dose of vitamin E and selenium during pregnancy].

The influence of peroral and parenteral supplementation with selenium compounds and vitamin E was studied in sows during gravidity, as exerted on the concentration of selenium in the blood serum of the tested sows. The experiment was conducted with 18 sows at the age of two to three years. The averge selenium level in the blood serum of the sows given an oral supplement of selenium and vitamin E was blood serum of the sows given an oral supplemnent of selenium and vitamin E was 2.278 mumol .1-1 on the 110th day of gravidity and 2.405 mumol .1-1 on the 20th day of lactation; adter s. c. injection of the preparation Selevit inj. Spofa the average concentration of selenium was kept at the same level from the 110th day to the 20th day of lactation (2.152 mumol .1-1). In the control sows the average value of blood serum selenium level was significantly lower at the same time intervals (1.772 and 1.645 mumol .1-1). Both ways of supplementation favourably influenced the selenium level in the blood serum of sows, particularly in the last stage of gravidity and in the first stage of lactation.

Animal Feed↗

PubMedDate not supplied

[The selenium content of milk].

The selenium content in milk of dairy cows from different countries varies between 2 and 60 micrograms/kg, because of differences in the selenium content in the feeds. With an increasing selenium content in the feed a decreasing part is secreted into the milk. A bigger part is utilized from natural selenium compounds in the feed than from selenite. In own investigations milk from Swedish cows had significantly lower selenium content during summer and autumn than during winter and spring (p less than 0,0001). The LS-means between different regions also differed significantly (p less than 0,0001). From the autumn of 1980 the feed manufacturers have been allowed to add sodium-selenite to concentrates and mineral feeds in amounts permitting a selenium content of 0,1 mg/kg DM in the total ration of dairy cows. The year after the selenium fortification was allowed, the LS-means for the selenium content of milk were 1 microgram/kg higher than the year before (p less than 0,001). In the southern parts of Sweden the selenium content was 8-10 and in the central and northern parts 7-9 micrograms/kg. These means were substantially lower than the figure of 15 micrograms/kg which was reported from the central part of Sweden two decades ago. The low selenium content in the milk during summer in some parts of Sweden could possibly mean that there is still a risk of selenium deficiency among the cattle. Anyhow the milk will not always cover the selenium requirement of the sucking or milkfed calf.

Animal Feed↗

PubMed1990

Transient hypothermia and hyperphagia induced by selenium and tellurium compounds in mice.

The effects of sublethal doses of selenite, selenate, selenocystine (Se-Cys) and selenomethionine (Se-Met) as well as of tellurite on body temperature and feeding behavior were examined in male ICR mice. Ten or 30 mumol/kg of chemicals were injected subcutaneously and body temperature was measured up to 4 h. In a separate experiment, the gastric content was weighted 4 h after injection. All chemicals except Se-Met induced both hypothermia and hyperphagia, suggesting that: (a) these two effects are related to each other; (b) among the chemicals tested, Se-Cys appears to be the most potent hypothermia inducer; (c) Se-Met is unique in that it has neither effect.

Animals↗

PubMed1996

Comparative cytotoxicity of 14 novel selenocysteine se-conjugates in rat renal proximal tubular cells.

Recently, Se-substituted selenocysteine conjugates were proposed as potential prodrugs to target biologically active selenol compounds to tissues containing high activities of cysteine conjugate beta-lyases, such as the kidneys. However, several selenium compounds are known to be relatively toxic compounds. In the present study, the cytotoxicity of 14 selenocysteine Se-conjugates was determined in freshly isolated rat renal proximal tubular cells (RPTC). The results of this study show that four selenocysteine Se-conjugates with alkyl substituents (methyl, ethyl, n-propyl, and n-butyl) did not cause significant cytotoxicity to RPTC up to concentrations of 500 microM after 90 min of incubation. Also, no effect was observed on mitochondrial functioning as indicated by the unaffected mitochondrial membrane potential (delta psi). Se-(i-Propyl)-selenocysteine, however, appeared to be a cytotoxic compound, causing time- and dose-dependent cytotoxicity, and caused a decrease of delta psi in remaining viable cells. Aminooxyacetic acid (AOAA) provided significant protection against cell death of Se-(i-propyl)-selenocysteine, pointing to involvement of cysteine conjugate beta-lyase. AOAA, however, did not prevent the decrease of delta psi. Differentially substituted Se-(phenyl)-L-selenocysteine and Se-(benzyl)-L-selenocysteine conjugates appeared to be cytotoxic to RPTC at a concentration of 200 microM, as indicated by increased cell death and a decreased delta psi in remaining viable cells. Within the Se-benzyl-series, Se-(4-methoxybenzyl)-L-selenocysteine was the most toxic conjugate, whereas Se-(4-chlorophenyl)-L-selenocysteine was the most toxic conjugate of the Se-phenyl compounds. The selenocysteine Se-conjugates with nonsubstituted phenyl and benzyl substituents were nontoxic at 200 microM, but caused significant cell death at a concentration of 500 microM. Preincubation with AOAA, an inhibitor of cysteine conjugate beta-lyase, provided only partial protection against the cytotoxicity of Se-(phenyl)-L-selenocysteine (500 microM) and Se-(4-methoxybenzyl)-L-selenocysteine (200 microM). AOAA did not protect against cytotoxicity of the other conjugates, suggesting direct effects of these compounds or involvement of alternative routes of bioactivation. This study demonstrates that cytotoxicity of selenocysteine Se-conjugates is strongly dependent on the nature of the Se-bound substituent. The nontoxic Se-(alkyl)-Se-conjugates may be promising candidates for further evaluation for chemopreventive activities.

Aminooxyacetic Acid↗

PubMed1995

Chemoprevention of cancer by organoselenium compounds.

A major research goal of our laboratories is the development of new organoselenium cancer chemopreventive agents with less toxicity compared to some of the historical selenium compounds, such as sodium selenite. Ideally, such agents would be employed to inhibit tumor development in different organs caused by a variety of chemical carcinogens, particularly those present in the human environment. A series of organoselenium compounds has been synthesized and evaluated for their chemopreventive efficacy in vivo. Parallel to these studies, short-term in vitro and in vivo assays were employed to understand the mechanism of action and to rapidly evaluate their efficacy in eventual long-term preclinical investigations. We demonstrated that one of the most effective of these organoselenium compounds, 1,4-phenylenebis(methylene)selenocyanate (p-XSC, Fig. 1), is capable of inhibiting tumors in the mammary glands, colon, and lung of laboratory animals. Dietary p-XSC inhibited mammary tumor development induced by 7,12-dimethylbenz(a)anthracene (DMBA) during both the initiation and post-initiation phases of carcinogenesis in female CD rats. p-XSC inhibited DMBA-DNA adduct formation in the mammary glands. In collaboration with other laboratories, we demonstrated that p-XSC inhibited thymidine kinase in mammary tumor cell lines derived from both humans and rats. Employing mammary carcinoma cell lines, p-XSC was also shown to inhibit cell growth and induce a dose-dependent increase in cell death by apoptosis. In these assays p-XSC appears superior to selenite and to its sulfur analog, 1,4-phenylenebis(methylene)thiocyanate. Dietary p-XSC decreased colon tumor induction by azoxymethane in F344 rats during both phases of carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1998

Selenium speciation in human body fluids.

Selenium consumed by humans in foods and in supplements exists in a number of different organic and inorganic forms including selenomethionine, selenocysteine, selenate and selenite. Animal and human studies have established that the bioavailability of the selenium depends upon the chemical form, which also influences the distribution of selenium in the body. These studies have included urinary excretion of selenium following ingestion of different forms of selenium and the response of tissue selenium concentrations and activities of functional selenoproteins to these selenium compounds. Selenomethionine is retained in tissue proteins to a greater extent than selenocysteine and the inorganic forms, but the selenium is not necessarily immediately available for functional selenoproteins. A number of other factors besides chemical form may also influence the bioavailability and distribution of selenium, including other dietary components, selenium status, physiological status and species. Knowledge of these factors and of speciation of selenium in foods, tissues and functional selenoproteins is important for the accurate assessment of selenium status. Speciation of selenium also has implications with respect to the determination of selenium requirements and to the investigation of relationships between selenium status and health and disease.

Biological Availability↗

PubMedDate not supplied

[Biochemical role of selenium].

The molecular mechanisms of selenium regulation of biochemical functions in animal and human tissues are presented in review. It is shown, that in spite of high toxicity selenium is an essential nutrient for people and animals. Taking into account deficit of this microelement in fodder it is necessary to use the selenium compounds in rations of domestic animals and poultry. The study of properties and characteristics of selenoproteins is important in discovering selenium role in regulation of cellular growth processes, the protective effect of this element in prevention of toxic action of heavy metals, xenobiotics and bacterial toxins on organism and anticarcinogenic effect of selenium.

Animals↗

PubMed1983

Mode of in vitro interaction of mercuric mercury with selenite to form high-molecular weight substance in rabbit blood.

Mode of interaction of mercuric mercury and selenite in rabbit blood was investigated in vitro. After the incubation of rabbit blood with 10(-5) M each of 203HgCl2 and Na2(75)SeO3, the amounts of both 203Hg and 75Se incorporated into erythrocytes were markedly larger than the case where the blood was treated separately with one of these compounds. Most of 203Hg and 75Se distributed into plasma and erythrocytes were found in high-molecular weight substance(s) (HMWS) fractionated by gel filtration at a molar ratio of 1:1. The 203Hg and 75Se in HMWS found in plasma and erythrocytes were hardly diffusable through the erythrocytes membrane. The formation of the HMWS containing mercury and selenium was observed in stroma-free hemolysate incubated with mercuric chloride and selenite, but not in plasma. Addition of reduced glutathione (GSH) to the plasma, however, gave the HMWS as reaction products containing equimolar amounts of mercury and selenium. Further the binding properties of selenium to proteins were studied in the plasma incubated with selenodiglutathione (GSSeSG) or with selenite in the presence of GSH. The results indicated that GSH, a cellular component, is essential for the formation of an active selenium compound from selenite and that the interaction of mercuric mercury and selenite in plasma in the presence of GSH may occur through the other mechanism than the formation of GSSeSG.

Animals↗

PubMed1991

Selenium: inhibition of microtubule formation and interaction with tubulin.

We have studied the interaction of Na2SeO3 with microtubule proteins and tubulin. This selenium compound inhibits the polymerization of MTP (half-inhibition occurred for Na2SeO3 10 microM), and to a lesser that of tubulin. This effect of selenite is related to the formation of disulfide bridges between tubulin sulfhydryl groups, inducing a conformational change of the protein. This is corroborated by the modified binding of colchicine and vinblastine in presence of selenium. The selenite inhibitory concentrations are similar to the toxic blood levels of selenium (40 microM).

Animals↗

PubMedDate not supplied

Selenium. Preclinical studies of anticancer therapeutic potential.

Selenium is a trace element that is essential to the human diet. Deficiency states have been described in both animals and humans. In addition, selenium compounds have demonstrated toxicity in humans, as well as in human tissues in culture. As early as 1956, one form of selenium was used as an antineoplastic agent in humans with some demonstrated activity. Recently, evidence in both tumor-bearing animals and human tumor cells in culture have confirmed an antitumor effect of potential clinical benefit. The mechanism of this cytoxic effect appears, at least in part, to relate to the property of some forms of selenium to oxidize critical sulfhydral groups in the cell. Evidence for this, and the resulting implications for the use of selenium in anticancer treatment, is presented in this manuscript.

Antineoplastic Agents↗