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[Selenium and the organism].

Selenium is an essential trace element for animals. It is biologically active as selenocysteine in the active centre of selenoproteins with enzymatic functions. Incorporation of selenocysteine occurs on the basis of genetic expression and selenium is the only trace element under direct genetic control. Selenocysteine can be considered the 21st amino acid with regard to its biosynthesis and incorporation into proteins. At least two types of selenoproteins are necessary for each animal cell, the first from the family of GSH-peroxidases and the second from the family of deiodinases. GSH-peroxidases are the most powerful antioxidant enzymes, which defend the cell and whole organism against oxidative damage and thus from oxidative diseases and disorders such as cardiovascular diseases, malignancies, bacterial or viral diseases, muscle dystrophy, arthropathy, arterial plaques, and others. GSH-Px have many other regulatory functions such as regulation of biosynthesis of prostaglandins, prostacycline, leukotrienes, and thromboxans. Deiodinases regulate the metabolism of biologically active triiodothyronine and thus thyroid hormone regulation of the whole organism. Selenoproteins act against cancerogenic effects of some organic molecules and bind heavy metals. Tissue-specific selenoproteins without a known biological function have been detected in some specialised tissues with a high priority for selenium. One of the regulators of selenoprotein synthesis is the selenium status of the organism. Its state an intake may be assessed by analyses of selenium indexes. The most often used indexes are serum selenium and urinary selenium. On the basis of its analyses in six regions of the Czech Republic, severe selenium deficiency has been found in inhabitants of this country, which is even profound for more distressed groups like growing children, pregnant and lactating women, and the elderly.

Animals↗

Effects of vitamin E and selenium supplementation on esophageal adenocarcinogenesis in a surgical model with rats.

Two well-known antioxidative nutrients, vitamin E and selenium, were used in this study to investigate possible inhibitory action against the formation of esophageal adenocarcinoma (EAC) in rats. In this model, carcinogenesis is believed to be driven by oxidative stress. Male Sprague-Dawley rats (8 weeks old) were divided into four groups and received esophagoduodenal anastomosis (EDA) surgery plus iron supplementation (12 mg/kg/week). Vitamin E and selenium were supplemented in the diet in the forms of alpha-tocopheryl acetate (750 IU/kg) and sodium selenate (1.7 mg Se/kg), which were 10 times the regular amounts in the basic AIN93M diet. At 40 weeks after surgery, all the EDA groups had lower body weights than the non-operated control group. Iron nutrition (hemoglobin, total serum iron and transferrin saturation) was normal as a result of iron supplementation after EDA. Vitamin E supplementation maintained the normal plasma level of alpha-tocopherol in EDA rats, but not those of gamma-tocopherol and retinol. Selenium supplementation increased the serum and liver selenium contents of the EDA rats. Histopathological analysis showed that selenium supplementation increased the incidence of EAC and the tumor volume. The selenium level in the tumor is higher than that in the duodenum of the same animal. Vitamin E supplementation, however, inhibited carcinogenesis, especially in the selenium-supplemented group. We believe that vitamin E exerts its effect through its antioxidative properties, and a high dose of inorganic selenium may promote carcinogenesis by enhancing oxidative stress.

Absorption↗

A case-control study of toenail selenium and cancer of the breast, colon, and prostate.

To study the possible role of dietary and supplementary selenium intake in the etiology of cancer, we carried out a case-control study of breast, colon, and prostate cancer in Montreal between 1989 and 1993. In this study, we were able to interview a total of 1,048 incidence cases of colon (402), breast (414) and prostate (232) cancer subjects and 688 population-based controls matched for age and gender. Of these, a total of 501 cancer cases and 202 controls produced toenail samples for their selenium concentrations, which were determined by neutron activation analysis. We found no association between toenail selenium and breast cancer (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.4-1.31) or prostate cancer (OR, 1.14; 95% CI, 0.46-2.83), though we did observe a statistically significant inverse association between toenail selenium level and the risk of colon cancer for both genders combined (OR, 0.42; 95% CI, 0.19-0.93; P = .009) and for female subjects (P = .050). We also found that nonsmoker case and control subjects had higher selenium in their toenail samples. This could be due either to the nature of tobacco, which reduces selenium absorption, or to smokers' consumption of certain foods containing less selenium. Further epidemiologic studies are required to clarify the role of selenium in the etiology of certain cancers.

Adolescent↗

Effect of selenium on human myocardial glutathione peroxidase gene expression.

OBJECTIVE: To examine the role of selenium (Se) in the expression and activity of selenium-dependent cellular glutathione peroxidase (GPX-1). METHODS: 46 patients with atrial septal defect or ventricular septal defect were separated into two groups, a control group (23 cases) and a Se supplementation group (23 cases). The Se supplementation group received 400 micrograms selenium per day for 7 days before surgery. We used biochemical techniques, atomic absorption, RT-PCR and cDNA sequence testing methods to evaluate and compare the changes during ischemia/reperfussion (I/R) in myocardial melondialdehyde (MDA) level, GPX activity and gene expression level, GPX cDNA nucleotide sequence, selenium and calcium and magnesium concentration. RESULTS: Before ischemia, taking selenium for 7 days did not change the selenium concentration in either plasma or blood cells in either group. The GPX mean activity level in the selenium group was slightly lower than that in the control group, and the MDA level was equal in both. After 30 minutes of reperfusion, the Se level in plasma and blood cells remained constant, while the myocardial Se concentration and GPX gene expression in the Se group increased significantly. The MDA level in the Se group reduced 4.2%, compared to an 8.2% rise in the control group. The mean level of GPX activity in the Se group was slightly lower than that in the control group. Both pre- and post-myocardial reperfusion, the Se group had a higher rate of myocardial GPX gene expression, and the nucleotide sequence was normal. These results indicate that supplementing Se is not likely to enhance myocardial GPX activity, but it could increase the GPX gene expression level, and thereby enhance the Se patients' myocardial antioxidant level during I/R, allowing free radicals to be scavenged as soon as they are generated. CONCLUSION: Se supplementation could increase myocardial selenium content and improve GPX gene expression during I/R, and in this way defend against free radical peroxide damage to the myocardium.

Adolescent↗

[Changes of selenium concentration in blood and placenta in intrahepatic cholestasis of pregnancy].

OBJECTIVE: To explore the effect of deficiency of blood selenium and placental selenium on the damage of histomorphology of the placentas in ICP. METHODS: We measured the selenium concentration by a catalytic polorographic method in blood and placenta and glutathione peroxidase (GSH-Px) activity by a 5,5'-dithionbis (2-nitrobenzoic acid) direct method in blood in 30 women with ICP (ICP group) and 30 normal pregnant women (control group). Furthermore, the features of the placentas (10 from control group and 10 from ICP group) pathologic changes were observed microscopically. RESULTS: (1) The selenium concentrations in blood (0.0389 +/- 0.0090) mg/L and placenta (0.3770 +/- 0.0964) mg/kg and the activity of GSH-Px (59.31 +/- 11.42) U in ICP group were found to be significantly lower than those in blood (0.0477 +/- 0.0094) mg/L and placenta (0.4554 +/- 0.0626) mg/kg and the activity of GSH-Px (68.48 +/- 10.47) U in control group, respectively (P < 0.002). (2) The activity of GSH-Px had a significant positive correlation with selenium concentration in blood in ICP group (r = 0.05498, P < 0.001) and in control group (r = 0.06234, P < 0.001). There was a positive correlation between blood and placental selenium concentrations in ICP group (r = 0.6473, P < 0.001). On the other hand, there was not correlation in women with normal pregnancies. (3) Placentas obtained from women with ICP had swelling and fibrinoid necrosis of villi, increasing number of syncytial sprouts, thickening of vasculo-syncytial membrane (VSM) and decreasing size of the intervillous space under light microscopy. Placentas from control group did not show the pathologic changes as mentioned above. CONCLUSIONS: As selenium constitutes the active part of GSH-Px, these results suggest that the placental selenium deficiency may lead to reduced placental GSH-Px activity and the antioxidative defence may have been defective which may be associated with the damage of histomorphology of the placentas in ICP.

Adult↗

Prediagnostic toenail selenium and risk of bladder cancer.

The association between several cancers and selenium status has been investigated in epidemiological studies. However, few results concerning bladder cancer have been reported thus far. The association between toenail selenium status and subsequent bladder cancer incidence was investigated in a prospective cohort study among 120,852 men and women aged 55-69 years at baseline (September 1986). The cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. Follow-up for incident cancer was established by record linkage to cancer registries until December 1992. The multivariable case-cohort analysis was based on 431 bladder cancer cases and 2,459 subcohort members, for whom toenail selenium levels were available. The age-, sex- and smoking-adjusted rate ratios (95% confidence intervals) for increasing quintiles of toenail selenium were 1.00 (reference), 1.09 (0.80-1.48), 0.55 (0.38-0.79), 0.63 (0.43-0.91), and 0.67 (0.46-0.97), respectively (P-trend < 0.01). Analyses with selenium as a continuous variable supported these findings. An inverse association between toenail selenium and bladder cancer risk was most pronounced among ex-smokers (P-trend < 0.01); was similar for subjects with high versus low intakes of beta-carotene, vitamin C, and vitamin E; and was mainly confined to invasive transitional cell carcinomas of the urinary bladder, irrespective of tumor morphology. We conclude that the evidence is in favor of an inverse association between selenium and bladder cancer risk.

Aged↗

Influence of selenium-enriched yeast supplementation on biomarkers of oxidative damage and hormone status in healthy adult males: a clinical pilot study.

The mechanisms responsible for the protective role of selenium against the development of prostate cancer remain to be determined (L. C. Clark et al., J. Am. Med. Assoc., 276: 1957-1963, 1996). In the present study, we tested the hypothesis that selenium supplementation reduces oxidative stress. A secondary aim was to determine whether selenium-induced changes in testosterone (T) metabolism may also be involved. To this end, we conducted a double-blind, randomized, placebo-controlled trial of 247 micro g selenium/day administered p.o. in the form of Se-enriched yeast. Study subjects were 36 healthy adult males, 11 blacks and 25 whites, 19-43 years of age. Supplementation occurred over the first 9 months, after which all subjects were placed on placebo for an additional 3 months. Blood and urine were collected at baseline and after 3, 9, and 12 months. In the selenium group, plasma selenium levels were 2-fold higher than baseline values after 3 and 9 months and returned to 136% of baseline after 12 months (P < 0.0001), whereas in the placebo group, levels were unchanged. A 32% increase in blood glutathione (GSH) levels was observed after 9 months in the selenium group only (P < 0.05). This change coincided with a 26% decrease in protein-bound GSH (bGSH) and a 44% decrease in bGSH:GSH ratios (P < 0.05). The changes in GSH and bGSH were highly correlated with changes in plasma selenium concentrations and may reflect a decrease in oxidative stress. No changes were observed in either group for plasma T, dihydrotestosterone (DHT) or DHT:T ratios, suggesting that selenium had no effect on the alpha-reductase involved in the conversion of T to DHT. A small but significant decrease in prostate-specific antigen levels was observed after 3 and 9 months (P < 0.001), and this difference disappeared after 12 months. Future trials will test the above hypothesis in prostate cancer patients and in subjects at high risk for prostate cancer.

8-Hydroxy-2'-Deoxyguanosine↗

[Concentration of selenium in serum of patients with ulcerative colitis].

Selenium deficiency may be implicated in the pathogenesis of some human diseases, including colon cancer. The incidence of carcinoma of the colon is increased in patients with ulcerative colitis. We measured the serum concentration of selenium in 22 patients with ulcerative colitis and 22 sex-, age-, height and weight-matched controls. Although no significant difference was found in mean serum selenium between patients and controls (patients: 0.92 mumol/l, controls: 0.79 mumol/l), the serum selenium level decreased with increasing extension of the disease. The differences between serum selenium concentrations in patients with proctitis-sigmoiditis, left-sided colitis and pan-colitis were statistically significant. No correlation was found between serum selenium concentrations and the sex, age, height, or weight of the patients. The inverse correlation between serum selenium concentration and the extension of the disease may be caused by a decreased absorption of selenium from the diseased colon in ulcerative colitis.

Adult↗

Plasma selenium concentrations in patients with euthyroid sick syndrome.

We evaluated plasma selenium concentrations in patients with euthyroid sick syndrome express by low serum triiodothyronine (T3) concentrations. Selenium status in these patients was compared with that found in patients with both untreated and treated hypothyroidism. Selenium concentrations in plasma were significantly lower in hospitalized patients with either euthyroid sick syndrome (0.99 +/- 0.37 mumol/L) or treated hypothyroidism (1.09 +/- 0.25 mumol/L) than in patients with untreated hypothyroidism (1.39 +/- 0.28 mumol/L). However, there was no significant, independent relationship between selenium and the thyroid function indices determined in this study. The strongest association was between serum albumin concentration and either selenium (r = 0.65), T3 (r = 0.58), or the molar ratio of T3 to thyroxine (r = 0.64). The decreased average selenium concentration appears to be associated with the hypercatabolic state of severely ill patients, as indicated by the serum albumin concentration; these patients should be considered for selenium supplementation and their selenium status should be monitored.

Euthyroid Sick Syndromes↗

[Effects of selenium and B-27 supplements on viability and differentiation of neural stem cell in newborn rat].

OBJECTIVE: To assess how trace element selenium and B27 supplements affect the neural stem cell (NSc) differentiation in vitro. METHODS: The development and differentiation of NSc from the newborn rat were observed with primary culture and subculture during treating by sodium-selenite, and selenium-methyl-cysteine (SMC). The immunocytochemistry techniques were used to identify the NSc and mature protein expression with neuron marker beta-tubulin, astrocyte marker GFAP, and oligodendrocyte marker CNPase. The neurosphere morphology and neurite outgrowth were observed. RESULTS: Adding the complete B-27 serum-free supplement, Selenium could promote the neurosphere viability, development and differentiation. Without selenium and B-27, neurosphere could not survive and differentiate. Without B-27 in the medium but there containing selenium, the neurosphere could promote the viability and development into neuron, astrocyte and oligodendrocyte, as compared with the no-containing B-27 and selenium groups, these differentiated cells might have more quantity, more branches and better morphological nerve net. The count of the neuron, astrocyte and oligodendrocyte was 11.2/Hp, 16.1/Hp and 9.3/Hp. CONCLUSIONS: The selenium should be very important for neural stem cells' survival. Selenium could promote the neurosphere cells differentiation and development.

Animals↗

Comparative determination of selenium in the serum of various animal species and humans by means of electrothermal atomic absorption spectrometry.

It was the goal of this paper to establish total selenium reference values for Switzerland in different animal species and in humans. To this purpose, a flameless atomic absorption method with deuterium background compensation utilizing a graphite furnace atomization system with a pyrolytic platform inside and palladium solution as matrix modifier was developed for the measurement of selenium in serum. The method was characterized by rapid performability, small sample requirement, acceptable detection limit (0.04 mumol/L) and precision and a linear range of measurement up to 4 mumol/L. The method proved to be suited for routine application in species with low selenium concentrations, such as cattle. It may be useful wherever small amounts of serum have to be analysed, e.g. in neonatology. Reference values of serum selenium concentration were determined in healthy subjects of various species, including man. They were as follows (min = 5%, max = 95% percentile values in mumol/L): humans (20-60 years): 0.78-1.48, humans (60-100 years): 0.61-1.73, horse: 0.36-1.68, dog: 1.90-4.31, cat: 3.60-10.09, cattle greater than 9 months: 0.10-0.82, calves 3-9 months: 0.19-0.65, sheep: 0.09-0.54, goat: 0.14-1.42, chicken: 1.68-4.28 and pig: 1.97-3.32. From the data it was concluded (i) that the serum selenium concentration depended on the amount of selenium in the food, and on the type of digestive tract; (ii) that carnivors had the highest and ruminants the lowest selenium values; and (iii) that up to 20% of the geriatric donors had inadequate selenium levels.

Adult↗

The evaluation of selenium status of sheep from the major production areas of Morocco.

In order to evaluate the selenium status of sheep in the major raising areas of Morocco, blood selenium concentration, erythrocyte glutathione peroxidase activity and feed selenium levels were determined. A total of 843 blood samples from sheep and 118 feed samples were analyzed. Results showed that 73% of sheep sampled had blood selenium concentrations below 100 ng/ml, and were deficient or marginal. Erythrocyte glutathione peroxidase activity was below 19 IU/g hemoglobin and feed selenium levels below 0.1 mg/kg on a dry matter basis. The erythrocyte glutathione peroxidase activity was highly correlated with blood selenium concentration over a wide range of selenium levels (r = 0.88, P less than 0.001, N = 622), indicating that the enzyme can be used as an indicator of the selenium status of grazing sheep.

Animal Feed↗

A survey of whole blood selenium concentrations of horses in Maryland.

We surveyed the whole blood selenium status of a randomly sampled population of horses from 4 contiguous counties in northern Maryland. Two hundred and two horses from 74 farms were sampled. Whole blood selenium levels greater than or equal to 0.100 parts per million (ppm) were considered adequate; blood levels less than 0.100 ppm were considered marginal or deficient. The average blood selenium concentration of the horses sampled was 0.137 ppm, with a standard deviation of 0.041 ppm. Blood selenium concentrations ranged from 0.050-0.266 ppm. Thirty-eight of 202 horses (18.8%) had a selenium level less than or equal to 0.099 ppm. Twenty-one of 74 farms (28.4%) had at least 1 horse with a selenium level less than or equal to 0.099 ppm. Animal husbandry practices had a significant influence on selenium status. Horses were more prone to having an abnormal selenium status if they were either maintained on pasture or used infrequently, or if their diet did not include mineral and vitamin supplements.

Animal Feed↗

Distribution of selenium-binding proteins in different tissues of the mouse and rat.

The distribution of selenium-binding proteins in specific tissues of mice and rats was examined by electrophoretic and immunologic techniques. Major selenium-binding proteins of 58K and 26K daltons were present in whole blood, erythrocytes, liver, duodenum, mammary tumors, kidney, testis, ovary and pancreas by electrophoretic analysis. By Western immunoblot it was evident that the 58K protein in plasma did not cross-react with the cellular 58 K protein. Furthermore, muscle did not exhibit any immunologically recognizable 58K protein. The antibody raised against mouse liver 58K recognized a similar protein in rat liver, kidney and testis. The 58K selenium-binding protein appeared to be concentrated in tissues enriched in G1 and the effect of hydroxyurea on selenium-binding protein levels suggested the 58K selenium-binding protein appeared to be made predominantly during the G1 phase of the cell cycle. Evidence is also presented that whole blood contains selenium bound to hemoglobin which supports prior evidence by other investigators. These results further support the evidence for tissue selenium-binding proteins other than glutathione peroxidase and document the immunological specificity and reactivity of a new antibody against a selenium-binding protein.

Animals↗

Influence of selenium status in merino weaners on resistance to trichostrongylid infection.

Weaned merino lambs, grazing pastures low in selenium, were used to investigate the effect of selenium status on immunity to trichostrongylids. Six weeks following selenium supplementation to 14 of the 27 sheep using intraruminal selenium pellets, 5000 Ostertagia circumcincta and 5000 Trichostrongylus colubriformis larvae were administered orally to all sheep. At four weeks after infection, the mean total worm burden in the selenium supplemented sheep (5537 +/- 343, n = 14) was not significantly different (P greater than 0.05) from that in the unsupplemented sheep (5614 +/- 374, n = 12) and faecal worm egg concentrations were also similar in the two treatment groups. At this time, mean red cell glutathione peroxidase activities in the supplemented and unsupplemented groups were 430 and 11 U g-1 haemoglobin, respectively, and clinical white muscle disease had been observed in the latter group. These results suggest that increasing selenium status of selenium deficient sheep by the use of intraruminal selenium supplementation, has a negligible effect on resistance to an artificial challenge infection of O circumcincta and T colubriformis.

Animals↗

Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line.

We have used a cloned cDNA for the major human selenoprotein, glutathione peroxidase (GPx), to assess the mode of regulation of human GPx gene (GPX-1) expression by selenium. When the HL-60 human myeloid cell line is grown in a selenium-deficient medium, GPx enzymatic activity decreases 30-fold compared with selenium-replete cells. Upon return to a medium containing selenium in the form of selenite, GPx activity in the cells starts to increase within 48 hours and reaches maximal (selenium-replete) levels at 7 days. Steady-state immunoreactive protein levels correlate with enzymatic activity. Cycloheximide inhibits the rise in GPx activity that accompanies selenium replenishment, indicating that protein synthesis is required for the increase. However, GPx mRNA levels and the rate of transcription of the human GPx gene change very little and thus appear to be independent of the selenium supply. Thus the human GPx gene appears to be regulated post-transcriptionally, probably cotranslationally, in response to selenium availability.

Blotting, Western↗

Plasma selenium content, platelet glutathione peroxidase and superoxide dismutase activity of residents in Kashin-Beck disease affected area in China.

The activity of platelet glutathione peroxidase, of platelet and erythrocyte superoxide dismutase and the concentration of plasma selenium and vitamin E were measured in two groups of residents in the Kashin-Beck disease affected area and in three from a non-affected area. Average plasma selenium levels and platelet glutathione peroxidase activity were significantly lower in the endemic area than in the non-endemic area, indicating that the residents in the endemic area are indeed in a low selenium status. There existed a significantly positive correlation, r = 0.94, n = 78, p less than 0.001, between platelet glutathione peroxidase activity and plasma selenium concentration over a range from 2 to 79 micrograms/L (mean values 5 to 66 micrograms/L). Platelet glutathione peroxidase also correlated well with plasma selenium in each group of residents with varying plasma selenium levels, demonstrating that determination of glutathione peroxidase activity in platelets can be used as an indicator for assessing low selenium status in humans. No significant difference of vitamin E levels was observed between the residents in the endemic and non-endemic areas. There were no statistically significant differences in the activity of superoxide dismutase between each two groups studied, showing that superoxide dismutase does not undergo a compensatory increase in the residents of low selenium status.

Adolescent↗

The effect of selenium on phagocytosis in humans.

The effect of selenium on immune responses in animals and humans is controversial. It has been reported that phagocytosis as a part of the immune function is affected by selenium deficiency. We conducted a study to investigate the effect of selenium on the phagocytic function of polymorphonuclear leukocytes (PMNs) in normal healthy individuals before and after selenium supplementation. Ingestion of sodium selenite 400 micrograms/day (182.8 micrograms pure selenium) resulted in a significant increase in plasma selenium levels. The phagocytic function of PMNs was measured by ingestion of Oil Red O paraffin droplets and chemiluminescence tests. The phagocytic function was increased, but the results before and after selenium supplementation were not significant. It was concluded that inorganic selenium was not an efficient stimulating agent of phagocytosis in humans.

Humans↗