Study of the action of Se and Cu on the growth metabolism of Escherichia coli by microcalorimetry.

The biological effect of Se and Cu²(+) on Escherichia coli (E. coli) growth was studied by using a 3114/3236 TAM Air Isothermal Calorimeter, ampoule method, at 37°C. From the thermogenesis curves, the thermokinetic equations were established under different conditions. The kinetics showed that a low concentration of Se (1-10 µg/mL) promoted the growth of E. coli, and a high concentration of Se (>10 µg/mL) inhibited the growth, but the Cu²(+) was always inhibiting the growth of E. coli. Moreover, there was an antagonistic or positive synergistic effect of Se and Cu²(+) on E. coli in the different culture medium when Se was 1-10 µg/ml and Cu²(+) was 1-20 µg/ml. There was a negative synergistic effect of Se and Cu²(+) on E. coli when Se was higher than 10 µg/ml and Cu²(+) was higher than 20 µg/ml. The antagonistic or synergistic effect between Se and Cu²(+) on E. coli was related to the formation of Cu-Se complexes under the different experimental conditions chosen.

Selenium and selenium-antagonistic elements in nutritional cancer prevention.

Selenium is an essential trace element with antioxidative, antimutagenic, antiviral and anticarcinogenic properties. There is increasing evidence that the dietary selenium intakes are sub-optimal in the populations of many countries and that human cancer mortalities would significantly decline if additional selenium was made available either through supplementation or the fortification of certain foods. An important property of selenium is its interaction with other elements that may be present in foods, the water, the workplace and the environment, e.g. As, Cu, Ni, Co, Cr, Mn, Zn, Cd, Sn, Pb, Hg, Bi, Mo, Ag, Au, etc. The sequestration of elements by selenium represents an efficient natural detoxification mechanism for some of these elements but also results in the physiological inactivation of selenium. Animal experiments confirm that the chronic exposure to low levels of these elements abolishes the cancer-protective effect of selenium. Human cancer is likewise significantly determined by the interactions of selenium with other elements, as evidenced by epidemiological, ecological and case-control studies. Cadmium, for example, is a key risk-increasing element for prostate cancer; for breast cancer, Cd, Cr, Zn are mainly contributing; for bronchial cancer (in smelter workers), Cd, As, Cr, Sb, Co, La, all these elements are in a reciprocal relationship with Se. While selenium remains the key cancer-protective trace element, the interpretation of its mode of action necessitates consideration of the effects of selenium antagonistic elements.

Effects of monosodium glutamate on food acceptance and toxicity of selenium in rats.

Food acceptance and toxic effects of feeding sodium selenite (Se) alone and in combination with monosodium glutamate (MSG), a taste enhancer were studied in the laboratory rat. Dose-dependent stimulation of daily food intake was observed with MSG offered in no-choice or bi-choice with the plain food. Consumption of pellets containing 0.05, 0.5 and 1.0% Se was significantly low than the plain or MSG containing pellets but their active ingredient was sufficient to cause mortality of rats. Food pellets containing both MSG and Se in no-choice feeding trial were not preferred by the rats, as their consumption remained low as compared to pellets containing only MSG. However, prior feeding on MSG containing pellets for two days increased the amount of intake of Se-containing pellets. No mortality of rats feeding on pellets containing different concentrations of MSG was recorded. Feeding on Se-containing pellets caused dose-dependent mortality on the third day of the trial. As compared to rats feeding on Se-containing pellets, the mortality rate was reduced in those provided Se in combination with MSG but the intake of active ingredient of Se in both these trials did not differ significantly. Decrease in death rate of rats feeding on Se in combination with MSG containing pellets suggested that addition of MSG to seleniferous food probably provide protection to some extent from the toxic effects of selenium. However, combination of excess doses of MSG and Se in food pellets caused mortality of all experimental animals.

NF-kappaB signaling pathway, not IFN-beta/STAT1, is responsible for the selenium suppression of LPS-induced nitric oxide production.

Upon stimulation of macrophages with lipopolysaccharide (LPS), Toll-like receptor 4 recognizes LPS, leading to expression of inducible nitric oxide synthase (iNOS), via MyD88/NF-kappaB and TRIF/IFN-beta/STAT pathways. Although selenium (Se) was reported to inhibit nitric oxide (NO) production, it is unclear which signaling pathway is inhibited by Se. Here, we investigated how Se inhibits NO production in LPS-stimulated RAW 264.7 cells. When the cells were pretreated with Se for 1 h followed by LPS treatment, iNOS mRNA expression and subsequent NO production declined significantly in a dose-dependent manner. Se inhibited IkappaBalpha degradation in the cytosol and NF-kappaB binding to its recognition site in the nucleus of the LPS-stimulated cells. Meanwhile, Se did not inhibit IFN-beta mRNA induction or STAT1 phosphorylation in the LPS-stimulated cells. These results suggest that Se down-regulates iNOS gene expression and NO production in the LPS-stimulated macrophages through inhibition of the NF-kappaB activation pathway but not the IFN-beta/STAT1 signaling pathway.

A study of Se-Hg antagonism in Glycine max (soybean) roots by size exclusion and reversed phase HPLC-ICPMS.

An attempt was made to study selenium (Se) and mercury (Hg) interactions in plants, specifically soybean (Glycine max), by inductively coupled plasma mass spectrometric detection. Greenhouse-cultivated plants were subjected to treatment with different regimens of Se and Hg and analyzed for their metabolized species in roots, stems, leaves, pods and beans. Most of the water-soluble Hg was found to be localized in the roots in association with Se in a high molecular weight entity, as identified by size exclusion chromatography. This entity was also extracted in protein specific isolate, but it resisted enzymatic breakdown. Complete breakdown of this high molecular weight species was accomplished by acid hydrolysis. Optimization of the conditions for acid hydrolysis is discussed. Hg and Se species found in root extract were studied by ion-pairing chromatography. In a sub-study, the Se distribution pattern was found to be unaffected by the presence of Hg, but the amount of Se assimilated was found to be higher in plants coexposed to Hg.

The role of zinc in life: a review.

Zinc is a common element in human and natural environments and plays an important part in many biological processes. Zinc, which is defined as an essential trace element, or a micronutrient, is essential for the normal growth and the reproduction of all higher plants and animals, and of humans. In addition, it plays a key role during physiological growth and fulfills an immune function. It is vital for the functionality of more than 300 enzymes, for the stabilization of DNA, and for gene expression. This review summarizes the role and manifestations of zinc in the environment and its importance for human health and metabolism, as well as its physiological role. Toxicity, teratogenicity, carcinogenicity, and immunological functions of zinc are outlined with particular reference to the properties of zinc as an antioxidant, and its role in cancer prevention.

Interactive effects of selenium and chromium on mammary tumor development and growth in MMTV-infected female mice and their relevance to human cancer.

Evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin C3H mice infected with the murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate] and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory effect of Se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. Exposure to Cr also altered the levels of Se in the liver and kidneys of the mice, indicating that Cr interacts with Se and affects its organ distribution. Chromium must be added to the list of Se-antagonistic elements that weaken or abolish the antitumorigenic effects of Se. These findings are relevant to human cancer as previous studies revealed the age-corrected mortalities from breast and other major forms of cancer in different countries to be inversely correlated with the dietary Se intakes, and directly correlated with the estimated intakes of Cr and of other Se-antagonistic elements. The presence of these elements in foods must be taken into account when estimating the optimal dose of supplemental Se for cancer risk reduction.

Antagonistic effect of scutellarin on the toxicity of selenium in rat livers.

Selenium has both nutritional function and toxicity according to its concentration and species. To counteract the toxicity of selenium, scutellarin was investigated. Wistar rats were supplemented with 40 microg Se/kg/d as sodium selenite, 40 microg Se/kg/d with 20 mg/kg/d scutellarin, and 20 mg/kg/d scutellarin, respectively, for 15 d. The mRNA levels and activities of glutathione peroxidase (GSH-Px) and thioredoxin reductase (TR), and the malondialdehyde (MDA) contents were measured. Reactive oxygen species (ROS) were detected by chemiluminescence assay, and tissue conformation was investigated by histological study. The results showed significant decreases of mRNA levels and activities of GSH-Px and TR and a significant increase of MDA content in livers of the Se-treated rats (p<0.05, compared with the control). Supplementation of scutellarin to the Se-treated group significantly inhibited the decreases of mRNA levels and activities, and the increase of MDA content (p<0.05, compared with the Se-treated group). Meanwhile, scutellarin-scavenged ROS generated in the mixture of sodium selenite, reduced glutathione, and oxygen. Liver injury was displayed in slices exposed to selenium at the present dose. The groups treated with both selenium and scutellarin or only scutellarin did not show significant tissue damage. Thus, scutellarin had an antagonistic effect against the toxicity of selenium.

Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase.

Recent clinical trials have documented that selenium significantly reduces the incidence of clinical prostate cancer. However, nothing is clearly known about the underlying molecular mechanisms by which selenium exerts its anti-cancer effect. This report provides evidence that selenium at micro-molar concentrations induces rapid apoptotic death in human prostate cancer cells, but not in normal prostate epithelial cells. Apoptosis involves activation of caspase 3 which plays a critical role in the cell death process. Interestingly, the apoptosis-inducing effect of selenium in prostate cancer cells is substantially alleviated by the 5-lipoxygenase metabolites, 5(S)-HETE and its dehydrogenated derivative 5-oxoETE, but not by metabolites of 12-lipoxygenase (12(S)-HETE) or 15-lipoxygenase (15(S)-HETE). Apoptosis is also prevented by their precursor, arachidonic acid, an omega-6, polyunsaturated fatty acid, presumably by metabolic conversion through the 5-lipoxygenase pathway. These results indicate that selenium's anticancer effect may involve induction of apoptosis specifically in prostate cancer cells sparing normal prostate epithelial cells, and that 5-lipoxygenase may be a molecular target of selenium's anticancer action. The present report warrants that care should be taken about high intake of dietary fat containing arachidonic acid or its precursor fatty acids when selenium is used for the management of prostate cancer, and suggests that a combination of selenium and 5-lipoxygenase inhibitors may be a more effective regimen for prostate cancer control.

Toxicity of selenium and other elements in food organisms to razorback sucker larvae.

Elevated selenium concentrations documented in water, sediment, and biota in irrigation drain water studies by U.S. Department of the Interior agencies and academia have raised concerns that selenium may be adversely affecting endangered fish in the upper Colorado River basin. The objective of the study was to determine the effects on endangered razorback sucker (Xyrauchen texanus) larvae from exposure to selenium and other trace elements in water and zooplankton collected from sites adjacent to the Colorado River near Grand Junction, CO. A 30-day study was initiated with 5-day-old larvae exposed in a 4 x 4 factor experiment with four food and four water treatments, and the biological endpoints measured were survival, growth, development, and whole-body residues of selenium. Mean selenium concentration in reference water (24-Road) was <0.7 microg/l, in reference food (brine shrimp) was 3.2 microg/g, at Horsethief was 1.6 microg/l in water and 6.0 microg/g in zooplankton, at Adobe Creek was 3.4 microg/l in water and 32 microg/g in zooplankton, and at Walter Walker was 13 microg/l in water and 52 microg/g in zooplankton. Although there were differences in concentrations of inorganic elements in water and biota among the three sites, selenium was apparently the only element elevated to concentrations of concern. Effects on survival were more prominent from dietary exposure compared to waterborne exposure. Selenium concentrations of >or=4.6 microg/g in food organisms adversely affected the survival of razorback sucker larvae. The onset of mortality in larvae exposed to food and water from Walter Walker seemed delayed compared to mortality in larvae exposed to food and water from Horsethief, which has been observed in two other studies. Elevated arsenic in one food source seemed to interact with selenium to reduce the toxic effects of selenium.

Effect of gold(I) compounds on the virulence of an amyocarditic strain of coxsackievirus B3.

Coxsackieviruses, especially B strains (CVB), are known etiological agents of myocarditis. Both amyocardititc and myocarditic strains exist and at least one amyocarditic strain, CVB3/0, can convert to virulence when passaged through selenium or vitamin E-deficient mice. Gold(I)-containing compounds, such as aurothiomalate (ATM) and aurothioglucose (ATG), can act as selenium antagonists. In this study, we examined the effect of intraperitoneal administration of equal doses of ATM or ATG on the virulence of CVB3/0. ATM but not ATG increased mortality in CVB3/0-infected mice. CVB3/0-infected mice treated with ATM had total necrosis of the pancreatic exocrine tissue. Heart damage also occurred in ATM-treated mice but did not correlate with mortality. Increased viral titers and persistence were observed in ATM-treated mice and, to a lesser extent, in ATG-treated mice. Thus, under our conditions, only ATM increased the virulence of CVB3/0, whereas ATG did not. On the other hand, both ATG and ATM inhibited thioredoxin reductase activity in heart and pancreas, but neither affected glutathione peroxidase activity. In contrast, dietary selenium deficiency reduces both enzyme activities. Thus, it is unlikely that these compounds affect virulence by acting as selenium antagonists.

Anticarcinogenic effects of selenium.

Selenium (Se) exerts its anticarcinogenic effects by multiple mechanisms. In the physiological dosage range, Se appears to function as an antimutagenic agent, preventing the malignant transformation of normal cells and the activation of oncogenes. These protective effects of Se seem to be primarily associated with its presence in the glutathione peroxidases, which are known to protect DNA and other cellular components from damage by oxygen radicals. Selenoenzymes are also known to play roles in carcinogen metabolism, in the control of cell division, oxygen metabolism, detoxification processes, apoptosis induction and the functioning of the immune system. Other modes of action, either direct or indirect, may also be operative, such as the partial retransformation of tumor cells and the inactivation of oncogenes. However, the effects of Se in the physiological dosage range are not attributable to cytotoxicity, allowing Se to be defined as a genuine nutritional cancer-protecting agent. The anticarcinogenic effects of Se are counteracted by Se-antagonistic compounds and elements. For maximal utilization of its cancer-protective potential, Se supplementation should start early in life and be maintained over the entire lifespan. In addition, exposure to Se antagonists and carcinogenic risk factors should be minimized by appropriate dietary and lifestyle changes.

Efeitos de níveis crescentes de enxofre na dieta de cordeiros submetidos a nível tóxico de selênio / Effects of sulphur crescent levels in diet of lambs submitted to selenium toxic levels

Vinte e cinco cordeiros não castrados, de 4 meses de idade e peso vivo médio de 30,2 kg, foram colocados em gaiolas metabólicas individuais de plástico e, após 14 dias de adaptação, receberam um dos seguintes tratamentos, por 90 dias: um controle (C) com 0,1 mg/kg Se na dieta `maisï pré-mistura mineral com 1 por cento de S, mais quatro tratamentos contendo o mesmo nível potencialmente tóxico de Se na dieta (5 mg/kg) e níveis crescentes de S na pré-mistura mineral, 1 por cento, 6 por cento, 11 por cento ou 26 por cento de S (respectivamente tratamentos I, II, III e IV). Num delineamento inteiramente casualizado, estudou-se o efeito antagônico do S na forma de flor de enxofre sobre o Se como selenito de sódio em nível potencialmente tóxico, através da análise dos teores de Se no soro, na lã, nas fezes, na urina e nos tecidos (fígado, rim, coração e músculo), hematócrito total e ganho de peso...

Effect of dietary fluoride on selenite toxicity in the rat.

Three factorial experiments were conducted to determine if high dietary fluoride (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and 150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on 8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were also unaffected by F. Liver Se concentration, however, was slightly (12%) but significantly (p < 0.025) reduced when the highest F and Se levels were combined. Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg). Therefore, further study focused on liver histology with treatments that eliminated the middle levels of selenite and F. Fluoride prevented the hepatic necrosis seen in selenite-toxic rats. Similar histological lesions were not observed for kidney or heart. Fluoride partially (26%) but significantly (p < 0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but there was no F effect on intracellular distribution of liver Se, glutathione levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the protective effect of F on selenite toxicity appears to be confined to liver pathology. The exact mechanism for this effect, however, remains unclear.

Interactive effects of selenium, methionine, and dietary protein on survival, growth, and physiology in mallard ducklings.

Concentrations of over 100 ppm (100 mg/kg) selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Both quantity and composition of dietary protein for wild ducklings may vary in selenium-contaminated environments. Day-old mallard (Anas platyrhynchos) ducklings received one of the following diets containing 22% protein: unsupplemented (controls), 15 ppm Se (as selenomethionine), 60 ppm Se, methionine supplemented, 15 ppm Se with methionine supplement, or 60 ppm Se with methionine supplement. In a second concurrent experiment the above sequence was repeated with a protein-restricted (11%) but isocaloric diet. In a third concurrent experiment all ducklings received 44% protein with 0, 15, or 60 ppm Se added. After 4 weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and histopathological lesions of the liver occurred. Antagonistic interactive effects occurred between supplementary methionine and Se, including complete to partial alleviation of the following Se effects by methionine: mortality, hepatic lesions, and altered glutathione and thiol status. With 11% protein, growth of controls was less than that with 22% protein, Se (60 ppm) caused 100% mortality, and methionine supplementation, although protective afforded less protection than it did with 22% protein. With 44% protein, ducklings experienced physiological stress, and Se was more toxic than with methionine-supplemented 22% protein. These findings suggest the potential for antagonistic effects of Se, methionine, and protein on duckling survival and physiology.

Selenium. Mechanistic aspects of anticarcinogenic action.

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

[Harmful elements versus iron, zinc and copper: their interactions in animals and humans. I. Mercury, tin, nickel, selenium, fluorine and aluminum]. / Pier wiastki szkodliwe a zelazo, czynk i miedz: interakcje w organizmie zwierzat i ludzi. Cz. I. Rtec, cyna, nikiel, selen, fluor, glin.

A literature survey was made of the interactions--in the organism--between some food contaminating elements (mercury, tin, nickel, selenium, fluorine, aluminium) and iron, zinc and copper. The harmful elements may disturb the mineral metabolism already at the stage of intestinal absorption. Moreover, they bring about changes in microelement distribution in the tissues and cells. On account of their approximately similar chemical structure, they compete for the sites of binding to some proteins, including enzymic ones. In this respect a special role is played by ++metallothionein, a protein with the ability of regulating free metal contents in the tissues and thus possibly displaying some detoxifying properties. Many mechanisms and relationships determining the interactions between the surveyed food contaminants and iron, zinc and copper remain, however, not elucidated.