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Selenium independent glutathione peroxidase activity associated with cationic forms of glutathione transferase in human heart.

Glutathione peroxidase activity with both hydrogen peroxide and cumene hydroperoxide was measured in the cytosolic fractions prepared from five human hearts obtained from post-mortem victims. In all the samples the activity with cumene hydroperoxide was higher than that obtained with hydrogen peroxide, suggesting that the selenium-independent glutathione peroxidase could also be present in this tissue. To determine its presence in heart tissue we fractionated the cardiac cytosol fraction on a column of Sephadex G-100 and measured glutathione peroxidase activity with both the substrates. Glutathione transferase activity was measured with 1-chloro-2,4-dinitrobenzene in the fractionated cytosol. The results indicated that a selenium-independent glutathione peroxidase activity was present (about 30% of total activity). Fractionation of the cytosol by gel filtration showed that peroxidase activity co-eluted with glutathione transferase activity. Subsequently the fractions containing glutathione transferase and selenium-independent glutathione peroxidase activity obtained from gel filtration experiments were passed through an affinity column and analyzed by isoelectric focusing. It was found that the selenium-independent glutathione peroxidase copurified with three isoenzymes of glutathione transferase which had a pI of 9.2, 8.9 and 8.6 respectively. In contrast the acidic isoenzymes of glutathione transferase lacked peroxidase activity. It is suggested that the selenium-independent glutathione peroxidase may play an important role in neutralizing oxygen toxicity in heart when the selenium-dependent glutathione peroxidase activity is impaired.

Chromatography, Affinity↗

Regional ecological risk assessment of selenium in Jilin province, China.

Integrating the biokinetic model of selenium with Monte Carlo analysis, this article carries out a quantitative study on ecological risk assessment in blood selenium levels of residents in Jilin province. The result shows that the established biokinetic model can be employed to predict the blood selenium levels of residents in a region. The predicted average blood selenium is 0.044 microg/ml and standard deviation is 0.013 microg/ml. Compared with the determined average blood selenium (0.043 microg/ml) and standard deviation (0.019 microg/ml), there was no obvious difference between each other (P > 0.05). The predictive risk degree (19.8%) is also similar to that of the Keshan disease occurrence (16.4%) of residents in Jilin province. The advance of the ecological risk assessment model of selenium offers a good example for the study on predictive models of other trace elements in the human body.

Animals↗

Whole blood selenium content in pregnant women.

The selenium content in the blood of pregnant women in the Valencian Community, Spain was determined until the end of gestation in order to assess its evolution and detect possible differences in relation to the values corresponding to non-pregnant women of fertile age. A total of 158 blood samples were obtained from 137 pregnant women. Samples were classified as: (a) first; (b) second; and (c) third trimester. Selenium was determined by a flow injection hydride atomic absorption spectrometric method (Seronorm whole blood was used as a quality control check). The selenium values obtained for the three trimesters followed a Gaussian distribution. The intervals for mean found were: (a) 75.7-85.5 micrograms/l; (b) 72.6-81.4 micrograms/l; and (c) 69.9-77.5 micrograms/l. Although a tendency to decrease was observed, no statistical significant differences between the three trimesters of the gestational period were observed. When we compare the values obtained with the blood selenium content of women of fertile age in the Valencian community (87.8-98.8 micrograms/l) by using an ANOVA test, statistically significant differences are found between the selenium values of women of fertile age and those corresponding to pregnant women. The differences, however, are very small and can be partially explained by the level of hemodilution during pregnancy, however, reference values of blood selenium contents in pregnant women should be taken into account.

Adult↗

Selenium contents of human milk and infant formulas in Spain.

The selenium content of Spanish human milk samples and different milk-based and soy-based infant formulas has been estimated by using a flow injection hydride atomic absorption spectrometric method after microwave digestion of the organic matter. Mean values of 11.4 +/- 3.7 and 10.7 +/- 4.6 ng/ml for colostrum and transitional milk, 8.4 +/- 3.4 and 5.3 +/- 1.9 ng/ml for mature milk at 1 month and up to 2 months respectively, was obtained. These values are close to those reported by others authors in Europe, and lower than the ones from the US, Japan and Korea. Selenium contents of the analyzed infants' formulas ranged from 2.7 to 9.6 ng/ml and from 1.8 to 7.5 ng/ml for soy and milk-based infant formulas, respectively. The variability in selenium contents is large, although mean values are close to the ones given in other European countries. Selenium contents are not usually given on the product. The selenium intakes were estimated assuming that infants fed only human milk. The intakes ranged from 2.0 to 8.4 micrograms/day and from 3.4 to 12.9 micrograms/day for colostrum and transitional milk, respectively, and from 2.6 to 10.3 micrograms/day for mature milk at 1 month, and from 1.2 to 8.3 micrograms/day for milk up to 2 months. The analyzed infant formulas provide significantly less selenium than the 10 micrograms/day corresponding to the recommended daily allowance for infants from 0 to 6 months.

Animals↗

Prediagnostic serum selenium and risk of cancer.

Selenium levels in serum samples collected in 1973 from 111 subjects in whom cancer developed during the subsequent 5 years were compared with those in serum samples from 210 cancer-free subjects matched for age, race, sex, and smoking history. The mean selenium level of cases (0.129 +/- SEM 0.002 micrograms/ml) was significantly lower than that of controls (0.136 +/- 0.002 micrograms/ml). The risk of cancer for subjects in the lowest quintile of serum selenium was twice that of subjects in the highest. Multivariate adjustment for geographical area and serum levels of lipids, vitamins A and E, and carotene, did not alter this relation. The association between low selenium level and cancer was strongest for gastrointestinal and prostatic cancers. Serum levels of vitamins A and E compounded the effect of low selenium; relative risks for the lowest tertile of selenium were 2.4 and 3.9 in the lowest tertiles of vitamins E and A, respectively.

Adult↗

Selenium: potent stimulator of tyrosyl phosphorylation and activator of MAP kinase.

Selenium, an essential biological trace element, is an integral component of several enzymes, and its use as a nutritional supplement has been popularized recently due to its potential role in low concentrations as an antioxidant and in higher concentrations as an anticancer agent. Selenium has also been reported to act as an insulin-mimetic agent with regard to normalization of blood glucose levels and regulation of some insulin-mediated metabolic processes. Little work, however, has been done concerning the pathway(s) by which this insulin-mimetic action occurs. In this study, we investigated the mechanism by which selenate exhibits insulin-mimetic properties in two different insulin responsive cell types, primary rat hepatocytes and 3T3 L1 adipocytes. We found that two proteins associated with the insulin signal cascade, the beta-subunit of the insulin receptor and IRS-1, increased in tyrosyl phosphorylation in the presence of selenium. The third identified selenium activated signal protein, MAP kinase, has been implicated not only in the insulin signal transduction pathway but also in other growth factor-mediated responses. Using an in-gel activity assay for MAP kinase, we demonstrated that both the p42 and p44 MAP kinases are activated when either hepatocytes or adipocytes are incubated in the presence of selenate. In addition to the activation of these specific proteins, we found that selenium also eventually profoundly affected overall tyrosyl phosphorylation. Our results therefore show that selenium not only increased the phosphorylation of proteins identified in the insulin signal cascade but also affected the overall phosphorylation state of the cell.

Adipocytes↗

[Dilated cardiomyopathy and selenium deficiency in AIDS. Apropos of a case].

Cardiac-related death of HIV-positive patients is not rare. The etiology of AIDS-associated dilated cardiomyopathies often remains unknown, even at autopsy. We report an observation associated to a severe deficit in selenium. The patient had been diagnosed as HIV-positive 2 years before. He presented Pneumocystis carinii pneumonia then Cryptococcus meningitis. Two months later he was hospitalized for pancreatitis and cachexia. He presented global heart failure that lead to death. No microorganism was found in myocardium at autopsy but plasma selenium was dramatically decreased (24 micrograms/L). The deficit in selenium has been associated to a dilated cardiomyopathy in non-AIDS patients. HIV-positive patients have an early decrease in plasma selenium, this concentration is dramatically decreased in malnourished patients. Selenium deficit might be the cause of some of the AIDS-related dilated cardiomyopathies and selenium supplementation might be useful in these patients.

Acquired Immunodeficiency Syndrome↗

New biologic functions--selenium-dependent nucleic acids and proteins.

Selenium occurs normally in living things as a highly specific component of certain enzymes and amino acid transfer nucleic acids (tRNAs). In bacteria, biosynthesis of essential selenoenzymes has been shown to be unaffected by wide variations in sulfur levels. The naturally occurring selenoenzymes so far identified from bacterial sources include glycine reductase, certain formate dehydrogenases, a hydrogenase, nicotinic acid hydroxylase, xanthine dehydrogenase and thiolase. The selenoenzyme, glutathione peroxidase, and three other selenoproteins of unknown function have been isolated from animals. In certain enzymes, e.g. glycine reductase, formate dehydrogenase, hydrogenase and glutathione peroxidase, the chemical form of selenium has been identified as selenocysteine. One enzyme, a bacterial thiolase, contains selenomethionine rather than selenocysteine. A labile, unidentified form of selenium is present in nicotinic acid hydroxylase, and by inference, xanthine dehydrogenase. The seleno-tRNAs serve as examples of a different type of biological macromolecule that is specifically modified with selenium. The major seleno-tRNAs in Clostridium sticklandii and Escherichia coli have been identified as glutamate and lysine isoaccepting species. The selenium-modified nucleoside is 5-methyl-aminomethyl-2-selenouridine (mnm5Se2U), which is the chemical analog of 5-methylaminomethyl-2-thiouridine, a previously identified minor base of E. coli tRNA2Glu. The seleno-tRNAGlu of C. sticklandii contains one gram atom of Se per mole of biologically active tRNA. Loss of Se from the modified nucleoside, mnm5Se2U, in this tRNA results in concomitant loss of glutamate charging activity suggesting that selenium is essential for interaction of the synthetase and its cognate tRNA.

Animals↗

Inhibitory effects of selenium on 1,2-dimethylhydrazine and methylazoxymethanol acetate induction of colon tumors.

Sprague-Dawley rats were injected weekly with either 1,2-dimethylhydrazine (DMH) or methylazoxymethanol acetate (MAM). Addition of 4 ppm selenium (sodium selenite) in the drinking water reduced the number of rats developing DMH-induced colon tumors from 13 to 6 groups of 15 each. The total number of tumors observed in these two groups was 39 in the DMH treated and 11 in the DMH plus selenium. The incidence of MAM-induced tumors was 93% (14/15) with the selenium additive and 100% (14/14) when MAM was administered without the selenium supplement. However, selenium decreased the total number of colon tumors induced by MAM to 42 tumors as compared to a total of 73 tumors in rats receiving only MAM. Both carcinogens induced tumors with a higher frequency in the transverse colon as compared to either the proximal or distal colon. Selenium at this level did not affect the weight gain of the animals.

Adenocarcinoma↗

Food supply abundant increase of serum selenium concentrations in middle-aged Dresden women between 1990 and 1996. DRECAN-Team. Dresden Cardiovascular Risk and Nutrition.

Serum selenium concentration was measured in middle-aged Dresden (East Germany) women in 1990 and 1996. In 1990, the serum concentration of selenium in middle-aged women was higher than in men living under the same environmental conditions (0.98 +/- 0.32 vs 0.82 +/- 0.19 micromol/l). In 1996, the serum concentration of selenium in middle-aged women was significantly higher than in 1990 (1.19 +/- 0.34 micromol/l). This increase seems to be caused by the changed foodstuff supply after the reunification of Germany. Selenium values did not correlate with age, blood pressure or daily energy intake. Moderate smoking and menopausal status did not influence the selenium levels. In 1990, the serum concentration of selenium was the highest in those women who consumed the lowest amounts of carbohydrates or fibers, or who had the highest consumption of meat, fresh fish or potatoes.

Adult↗

Effects of nickel chloride on reproduction of the rat and possible antagonistic role of selenium.

Nickel (10-100 ppm added as NiCl2) was studied to determine its effects on reproduction of Wistar rats. In nine experimental groups, females, males or both were exposed to nickel in drinking water. In one female group and one male group, the drinking water was also supplemented with 0.3 ppm selenium (added as Na2SeO3). Breeding success and the growth and viability of pups were recorded. Nickel, copper and zinc concentrations in kidneys, liver and skin (with fur) of the females, males and pups were determined with an atomic absorption spectrophotometer. In addition, histology of the male testes (from control and nickel-exposed groups) was studied. The female exposures started 14, 28 or 100 days before copulation and continued during pregnancy and lactation. When the males were exposed (for 28 or 42 days before copulation), NiCl2 reduced both the number of pregnancies and the number of pups born. In the testes, NiCl2 induced shrinkage of the seminiferous tubules, which seemed to close some of the tubules. In the tubules, NiCl2 decreased the number of basal spermatogonia. When the females or both parents were exposed to NiCl2, pup mortality during lactation was high. However, when the females were drinking NiCl2 supplemented with selenium, all the pups survived and development of the total mass of the litters was even better than in the control group. In the same way, in males, selenium supplementation of the drinking water protected those pups that were born; but fertility was lower than with the control treatment. In the tissues studied, nickel accumulated most in the kidneys and then in the liver and skin. In each type of organ, there was a clear dose response relationship. In the pups, in particular, selenium (given to the females) increased the amount of nickel in tissues compared with corresponding administration of nickel without selenium. In summary, selenium seemed to counteract the deleterious effects of NiCl2 on the reproduction of rats.

Animals↗

Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis.

The cancer chemopreventive effect of selenium cannot be fully accounted for by the role of selenium as a component of the antioxidant enzyme glutathione peroxidase, which suggests that chemoprevention occurs by another mechanism. Several studies have shown that thiol oxidation and free radical generation occur as a consequence of selenium catalysis and toxicity. In the present study, we evaluated three different selenium compounds; selenite, selenocystamine, and selenomethionine to determine the relative importance of the prooxidative effects of these compounds with regard to their ability to induce apoptosis. The experimental results suggest that, in addition to supporting an increased activity of glutathione peroxidase, an antioxidant function that the three selenium compounds did with equal efficacy, catalytic selenite, and selenocystamine generated 8-hydroxydeoxyguanosine DNA adducts, induced apoptosis and were found to be cytotoxic in mouse keratinocytes. The noncatalytic selenomethionine was not cytotoxic, did not generate 8-hydroxydeoxyguanosine adducts and did not induce cellular apoptosis at any of the selenium concentrations studied. In keratinocytes, apoptosis may be initiated by superoxide (O2*-) and oxidative free radicals that are generated by selenite and selenocystamine, but not by selenomethionine.

Animals↗

Longitudinal study on selenium content in human milk particularly during early lactation compared to that in infant formulas and cow's milk in Japan.

239 samples of human breast milk were collected from 36 healthy Japanese women. Selenium content of the samples was determined mainly by highly sensitive fluorometric analysis with 2,3-diaminonaphthalene. The highest selenium content, 247 micrograms/kg, was found on the first day postpartum. The arithmetic mean of selenium content was higher in colostrum (< 4 days) 47 micrograms/kg (SD 42, n = 116) than in transitional milk 24 micrograms/kg (SD 13, n = 87) or in mature milk (> 10 days) 10 micrograms/kg (SD 4, n = 36). Selenium content was also determined for six brands of commercial infant formula powder (32-58 micrograms/kg) based on cow's milk, seventeen brands of cow's milk (10-25 micrograms/kg) and eight brands of powered cream for cofee (9-162 micrograms/kg). The average selenium content was significant lower in the liquid formula prepared for infant lactation, 6.0 micrograms/L, than in the human colostrum and transitional milk. The dietary selenium intake of newborns fed on colostrum is estimated to be in the range of 2-12 micrograms per day.

Animals↗

Effect of selenium supplementation on biological constants and antioxidant status in rats.

Oxygen-derived free radicals are currently suspected to be widely involved in the aetiology of several clinical disorders. In animals as well as in man, antioxidant trials are often undertaken to prevent oxidative stress. Among antioxidant molecules selenium has been largely studied. This study shows that plasma Se level is not a good index of Se status in the organism, at least at high levels of selenium. Red blood cell Se seems to be a more reliable index of Se status and could replace plasma Se level in the supplementation trials both in animals and humans. Se supplementation did not result in a significant decrease in oxidative stress markers as evaluated by blood and tissue malondialdehyde contents in healthy animals. Furthermore, heart function was altered and plasma Alanine aminotransferase activity was significantly increased in the selenium-supplemented group, which could reflect a slight subtoxic effect of selenium supplementation at the level used here. In view of the results presented, the maximum selenium content in animal diet in selenium supplementation experiments should not be higher than 2 mg/kg.

Animals↗

Protein-bound selenium in the seeds of coco de mono (Lecythis ollaria).

High selenium concentrations (7-12 g/kg dry mass) were found in the seeds of the selenium-accumulator plant coco de mono (Lecythis ollaria). In order to obtain information on the protein-bound part of selenium in extracts of these seeds, dialysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used combined with neutron activation analysis. Extractions were carried out at pH 4.5 and 7.5. In both cases about 90% of the element was dissolved. Of the extracted selenium only 9% was shown to be firmly bound to proteins at pH 4.5 and 29% at pH 7.5. For the protein-bound selenium, concentrations of 0.7 g and 2.4 g per kg of seeds and 40 and 25 g per kg of extractable protein were determined at pH 4.5 and 7.5, respectively. By analyzing the protein fractions separated by SDS-PAGE the element was found to be present in extremely selenium-rich proteins with molecular masses below 20 kDa.

Chemical Fractionation↗

Longitudinal study of the dietary selenium intake of exclusively breast-fed infants during early lactation in Korea and Japan.

213 samples of human breast milk were collected from 51 healthy Korean women. Selenium content of the samples was determined by atomic absorption spectrometry with hydride generation. The selenium content of Korean milk decreased with increase of days after birth: The arithmetic mean of selenium content was higher in colostrum (< 4 days) 34 micrograms/kg (SD +/- 11, n = 44) than in transitional milk 21 micrograms/kg (SD +/- 8, n = 78) or in mature milk (> 10 days) 13 micrograms/kg (SD +/- 6, n = 91). The daily dietary selenium intake of 0-1 month aged Korean infants fed on breast milk is estimated to be around 10 micrograms per day (3 micrograms/kg body weight) regardless of days postpartum, resulting from the calculation of our selenium data and daily milk intake during early lactation. The same result on selenium intake for Japanese newborns, as well as Korean infants, is also estimated to be around 10 micrograms per day (3 micrograms/kg body weight) regardless of days postpartum.

Adult↗

Effect of selenium-enriched broccoli diet on differential gene expression in min mouse liver(1,2).

Multiple intestinal neoplasia (Min) mice are a good model for investigating the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli effectively reduces colon cancer susceptibility. Although colon cancer cells mainly metastasize to the liver, little is known about the effects of selenium-enriched broccoli on gene expression in mouse liver. To better understand the protective role for selenium-enriched broccoli in tumorigenesis, a gene profile of the mouse liver was analyzed. Mice were fed either 0.11 mg selenium/kg control diet or 2.1 mg selenium/kg selenobroccoli diets for 10 weeks. Use of mouse pathway finder-1 GEArrays revealed that selenium-enriched broccoli moderately increased ikBalphakappaB, hsp86, gadd45 gene transcripts. In addition, analysis of the binding of liver nuclear proteins to (32)P-labeled probes demonstrated that selenium-enriched broccoli enhanced the binding of transcription factor p53, NFkappaB, AP-1 to their cis-acting elements. Collectively, these results suggest for the first time that selenium-enriched broccoli activates certain pro-apoptotic genes linked to p53, NFkappaB and stress signal pathways in response to "danger signals" such as tumorigenesis.

Animals↗

Selenium pretreatment prevents bacterial translocation in rat intestinal ischemia/reperfusion model.

Protective role of selenium against free radical damage was first demonstrated in the heart and this effect was further questioned in other systems. In the present study, the effects of exogenously administered selenium on intestinal fine morphology, lipid peroxidation, and bacterial translocation (BT) in experimental intestinal ischemia/reperfusion (I/R) model were examined. Thirty-two male Wistar rats weighing 250-300 g were randomized into four groups. Sham group (n=8) underwent laparotomy only. In the I/R group (n=8), laparotomy was performed and the superior mesenteric artery was occluded using an atraumatic microvascular clamp for 30 min. In corresponding selenium-treated groups (n=8 each), sodium selenate was given 0.2 mg kg(-1)day(-1) intraperitoneally (i.p.) for 3 consecutive days, prior to surgery for either laparotomy only or with I/R. Twenty-four hours later, tissue samples from liver, spleen, and mesenteric lymph nodes were obtained under sterile conditions for microbiological analysis and further evaluation of I/R-induced intestinal injury. Ileum samples were fixed in 10% formaldehyde for histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, and liver was significantly higher than other groups (P<0.05). Selenium supplementation prevented I/R-induced BT and significantly reduced the I/R-induced intestinal injury (P<0.05). Tissue MDA levels from the ileum specimens of selenium-treated rats were significantly lower than that of the I/R group (P<0.05). Our results provide evidence that the relationship between BT and lipid peroxidation in intestinal tissue is crucial. Selenium pretreatment reduces lipid peroxidation which contributes to the maintenance of intestinal mucosal integrity.

Animals↗