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Effects of cadmium treatment on selenium-dependent and selenium-independent glutathione peroxidase activities and lipid peroxidation in the kidney and liver of rats maintained on various levels of dietary selenium.

Rats fed a basal, low-selenium diet, or this diet supplemented with 0.1 ppm and 1.0 ppm selenium and treated with cadmium, showed significant reductions in the activity of the selenoenzyme glutathione peroxidase in kidney and liver. Cadmium treatment resulted in a significant increase in the activity of selenium-independent glutathione peroxidase activity in the liver of selenium-supplemented rats. Selenium-independent glutathione peroxidase activity was significantly reduced in the kidney of rats fed the basal low-selenium diet. There was no significant increase in lipid peroxidation in any of the groups studied. Cadmium concentrations in the kidney and liver of these animals ranged from about 250 to 700 micrograms Cd/g tissue, dry weight.

Animals

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.

Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism.

Child

Selenium and human lactation in Australia: milk and blood selenium levels in lactating women, and selenium intakes of their breast-fed infants.

A series of 20 mother-infant pairs were studied in Brisbane, Australia, at 6-12 weeks postpartum. The mean selenium concentration in maternal blood was 101 (SD +/- 19) ng/g and in maternal serum 81(+/- 15) ng/g; serum values appeared low in comparison with those reported for lactating women from Japan and the USA, but similar to those from Finland and from a previous Australian study. Breast milk selenium concentrations (11.9 +/- 3.5 ng/g) were also low by international standards, but not as low as in New Zealand or Scandinavia. There was no correlation between selenium concentrations in milk and blood (or serum). The infants' 24-h breast-milk intakes were 856 +/- 172 g, and their 24-h selenium intakes 10.7 +/- 4.1 micrograms (compared to the Australian RDI of 10 micrograms).

Adolescent

The selenium state of healthy children. I. Serum selenium concentration at different ages; activity of glutathione peroxidase of erythrocytes at different ages; selenium content of food of infants.

The selenium concentration of serum is age-dependent. The median value at birth (chi=50 X 10(-9)g/ml) amounts to half of the median value of adults (chi=102 X 10(-9)g/ml). After a decrease in early infancy to chi=34 X 10(-9)g/ml it steadily increases to chi=58 X 10(-9)g/ml in the second half of the first year, to chi=82 X 10(-9)g/ml in 1--5 year old children, and to chi=92 X 10(-9)g/ml in school children. The activities of the selenium containing enzyme glutathione peroxidase of erythrocytes are also reduced in early infancy (chi=7.2 +/- 0.36 U37/g Hb), whereas the enzyme activities of cord blood erythrocytes (chi=8.72 +/- 0.76 U37/g Hb) are in the same range as those of older children or adults. The selenium content of some commercially available milk formulas for infants are lower than those of human and cow's milk.

Adolescent

Estimation of the relative bioavailability of inorganic selenium sources for poultry. 2. Tissue uptake of selenium from high dietary selenium concentrations.

An experiment was conducted with 192 day-old male Cobb chicks to study tissue uptake of Se as an estimate of the bioavailability of supplemental inorganic Se sources fed at high dietary concentrations. A basal corn-soybean meal diet (.18 mg Se/kg diet, dry matter basis) was supplemented with 0, 3, 6, or 9 mg Se/kg diet (as-fed basis) as either reagent grade Na2SeO3, CaSeO3, or Na2SeO3 plus fumed amorphous carrier or 6 mg Se/kg diet as either Na2SeO4 or Se metal, and fed for 1 wk. No toxic effects were noted as expressed by mortality; however, there was a reduction (P less than .01) in feed intake and daily gain when 9 mg Se/kg diet was fed, suggesting onset of toxicosis. Selenium concentration in liver, kidney, muscle, and plasma increased linearly (P less than .01) as dietary Se increased from all sources. Selenium metal produced lower (P less than .01) Se concentrations in kidney and muscle than other supplemental sources. Multiple regression slope ratios were used to estimate relative bioavailability values of 100, 103, 99, 112, and 83 for Na2SeO3, CaSeO3, Na2SeO3 + carrier, Na2SeO4, and Se metal, respectively. When these ratios were corrected for the analyzed dietary Se concentration, relative values were 100, 96, 94, 109, and 81 for the above sources, respectively.

Animals

Selenium intake and serum selenium in Finland: effects of soil fertilization with selenium.

Since fall 1984 all agricultural multinutrient fertilizers in Finland have been supplemented with sodium selenate in an attempt to improve the nutritional quality of local foodstuffs known to be exceptionally low in selenium. The intervention has been effective from the growing season 1985 and it has affected practically all domestic agricultural products. From 1984 to 1986 the mean Se concentration of different foods increased. The mean Se intake of the population, calculated on the basis of food consumption statistics and from the data of urinary Se excretion, as well as the average serum Se concentration of both urban and rural people increased also during the same period. Enrichment of fertilizers with sodium selenate seems an efficient and predictable way of increasing the Se concentration of foods and the Se intake of people in low-Se areas.

Adult

Relationship of selenium concentrations in blood of calves to blood selenium of the dam and supplemental selenium.

Selenium status of dam, injected Se, and dietary Ca on calf blood Se concentrations were determined in two trials. Blood was collected from heifer calf and dam pairs at parturition. Half of the calves were injected intramuscularly with .0825 mg Se/kg body weight at birth while the other half received no Se injections. The concentration of Se in the blood of the dam had a significant effect on blood Se of calves at wk 0, 1, and 3, whereas injected Se did not significantly affect blood Se concentrations in the calf until wk 10. In a separate trial, whole blood and plasma Se were significantly correlated at birth in calves, but plasma Se was only about one-third the concentration of whole blood. The concentration of dietary Ca in the calf starter did not significantly affect blood Se, but a quadratic relationship was suggested. Plasma Zn in calves was elevated at birth and then declined with age whereas plasma inorganic P increased with age. Early postnatal concentrations of Se in blood of calves are largely a function of the dam; thus, in areas of low Se intakes, Se supplements for the dam are important.

Animals

Estimation of the relative bioavailability of inorganic selenium sources for poultry. 1. Effect of time and high dietary selenium on tissue selenium uptake.

An experiment was conducted with male broiler-type chicks to study the effect of time and high dietary Se concentration on tissue Se uptake. A basal corn-soybean meal diet (.2 mg/kg Se, DM basis) was supplemented with 0, 3, 6, or 9 mg/kg Se (as-fed basis) as Na2SeO3 and fed ad libitum for 1, 2, or 3 wk. No toxic effect of Se was observed as expressed by mortality; however, there was a reduction in daily feed intake (P less than .01) at 6 and 9 mg/kg added Se, particularly at 3 wk, suggesting developing toxicosis. Selenium concentration in all tissues studied increased linearly (P less than .001) as dietary Se increased, especially in kidney and liver. Coefficients of determination and lambda criterion values were greatest in plasma, followed by liver, muscle, and kidney. It appeared that 1 wk would be an adequate length of time for further Se bioavailability studies based on tissue Se uptake from diets containing 3 to 9 mg/kg added Se.

Animals

Comparative utilization of fish selenium and inorganic selenite by rats of normal selenium status.

Rats of a normal selenium status were fed diets based on fish (rainbow trout) as the main protein source. A 4-week experiment with three dietary groups (low fish selenium, high fish selenium and selenite supplementation) was performed, and the selenium absorption, excretion and retention were recorded. Samples of blood serum, liver, kidneys, testes, hairs, spleen, lungs, heart, brain and skeletal muscle were collected for analysis of selenium. Glutathione peroxidase activity was measured in the blood serum. A selenium supplementation of approximately 1 mg/kg (high fish selenium and selenite group) yielded a selenium retention of only 7% of the intake, while in the group with a dietary selenium concentration of approximately 0.1 mg/kg (low fish selenium group) the selenium retention was 50%, resulting in almost the same absolute selenium retention in all three groups. The liver and kidneys showed the highest accumulations of selenium, reflecting the participation of these organs in the excretion of surplus selenium. The highest relative uptake of selenium was recorded in the testes, which increased equally in all dietary groups. The selenium concentration in the other tissues investigated, as well as the glutathione peroxidase activity in the blood serum responded little to the selenium supplementations. These results showed that the selenium levels normally found in fish were sufficient to satisfy the need for this element in rats of a good selenium status, and that inorganic selenite was absorbed and excreted at a high rate already after 1 week.

Animals

Biochemical studies of a selenium-deficient population in China: measurement of selenium, glutathione peroxidase and other oxidant defense indices in blood.

Selenium deficiency is necessary for the development of the cardiomyopathy known as Keshan disease. Healthy boys and men (19-22 per group) from a low selenium area (Dechang County) and from an area where sodium selenite was added to salt (Mianning County) were studied. Keshan disease was endemic in Dechang but occurred rarely in Mianning. After an initial blood sampling, each subject received daily selenium supplements (100 micrograms selenium for boys and 200 micrograms for men) as sodium selenate for 14 d. Blood was sampled again at 7 and 14 d. Boys from Dechang had blood selenium levels similar to levels reported for patients with Keshan disease. Plasma glutathione peroxidase activity in boys and men from Dechang was 33 and 43%, respectively, of values from the corresponding groups in Mianning. Comparison of plasma selenium concentrations in boys and men from Dechang gave values of 33 and 38%, respectively, of the corresponding groups in Mianning. Selenium status did not affect red blood cell superoxide dismutase or catalase activities. Plasma vitamin E concentration was below the normal range in all groups but was unaffected by selenium status. Measurements of plasma malondialdehyde revealed no difference between subjects from Dechang and subjects from Mianning. Selenium supplementation raised plasma glutathione peroxidase activity and plasma selenium concentration in all groups. Groups with higher plasma selenium concentration had relatively smaller increases in glutathione peroxidase activity than in selenium concentration. These results characterize the selenium deficiency in subjects at risk for developing Keshan disease. The results obtained with supplementation of selenium indicate the presence of additional plasma forms of selenium besides glutathione peroxidase.

Adolescent

Comparison of whole blood selenium values and erythrocyte glutathione peroxidase activities of normal individuals on supplementation with selenate, selenite, L-selenomethionine, and high selenium yeast.

The selenium levels and the glutathione peroxidase activity GSH-PX of whole blood and of erythrocytes, respectively, were determined in 139 normal Danes and related to sex and smoking habits. No differences were found in relation to sex apart from a higher GSH-PX activity of females when assayed with tertiary butyl hydroperoxide. Smokers showed significantly lower selenium values than non-smokers (p less than 0.05), but the two groups had identical GSH-PX activities. Individuals from the above-mentioned group were divided into four groups, receiving daily oral doses of 200 micrograms of selenium in the form of selenite, selenate, L-selenomethionine, and selenium as contained in yeast. Whole blood selenium values and the erythrocyte glutathione peroxidase activities were determined during three months of supplementation followed by a withdrawal period of four months. Both the inorganic selenium compounds and the organic derivatives gave rise to steady state levels of GSH-PX after one month of supplementation. However, the selenium levels in the groups receiving organic selenium showed a steady rise during the whole period, whereas those supplemented with inorganic selenium leveled off after a period of one to three months. The data for smokers and nonsmokers revealed identical results when organic selenium was supplemented. However, selenite gave rise to significantly higher selenium levels and GSH-PX activities in smokers than in non-smokers. Less significant (p less than 0.08) elevations of both parameters were also observed among the smokers in the selenate group. By taking both the selenium level and the GSH-PX activity into consideration, organic selenium (i.e., L-(+) selenomethionine) was judged to be more bioavailable than selenite and selenate.

Adult

Hematologic data of selenium-deficient and selenium-supplemented rats.

Effect of dietary selenium as sodium selenite on in vivo hematological parameters of Sprague-Dawley rats was examined over a 7-month period. Dietary selenium did not alter total hemoglobin, hematocrits, erythrocyte counts, or the osmotic fragility pattern of rat blood. Selenium-excessive (1.0 ppm) rats showed slightly lower but not significantly lower methemoglobin levels than selenium-adequate (0.1 ppm) or selenium-deficient rats. Platelet counts tended to be higher in selenium-excessive rats and lower in selenium-deficient rats than in selenium-adequate rats, but the differences were not statistically significant. No clear trends were observed regarding the effect of dietary selenium on total leukocyte and differential leukocyte counts. After 7 months of dietary treatment blood glutathione peroxidase activity in selenium-deficient rats and in selenium-excessive rats was 16.8% and 142.2% of the activity in selenium-adequate rats. The results indicate that long-term selenium deficiency in rats produces no abnormal hematological parameters or any compensated hemolytic anemia in vivo.

Animals

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.

Adult

The effect of selenium supplementation on selenium status of patients receiving chronic total parenteral nutrition.

Patients receiving long-term total parenteral nutrition (TPN) are at risk for selenium deficiency. The purpose of this study was to determine the effect of parenteral selenium as selenious acid on the selenium status of seven long-term TPN patients. Patients received a dosage of zero, 80, or 160 micrograms Se/day for 1 month each. The measures of selenium status used were selenium levels in plasma and glutathione-peroxidase activities in erythrocytes and platelets. Urinary selenium excretion was measured. Control subjects were selected to match the sex, age, and weight of the patients. With increasing levels of parenteral selenium, there was increasing plasma selenium concentration as well as erythrocyte and platelet glutathione-peroxidase activity. There was no statistical difference between the patients during the time they received the 160 micrograms parenteral selenium treatment and the control subjects for platelet glutathione-peroxidase activity. At the 160 micrograms Se/day level, patient plasma selenium concentrations increased from 28% to 58% of the control levels. Four patients were studied after they returned to the 80 micrograms parenteral selenium/day from the 160-micrograms Se/day treatment. With decreasing parenteral selenium, three patients had decreasing platelet glutathione-peroxidase activity, while plasma selenium concentration decreased in two patients. These data suggest that some patients receiving long-term parenteral nutrition should receive parenteral selenium.

Adult

Elevation of rat liver mRNA for selenium-dependent glutathione peroxidase by selenium deficiency.

Selenium-dependent glutathione peroxidase (Se-GSH-Px, GSH-H2O2 oxidoreductase EC 1.11.1.9) is the best characterized selenoprotein in higher animals, but the mechanism whereby selenium becomes incorporated into the enzyme protein remains under investigation. To elucidate the mechanism of insertion of selenium into Ge-GSH-Px further, we have systematically analyzed and compared the results of Western blot, in vitro translation immunoprecipitation, and Northern blot experiments conducted with liver proteins and RNAs obtained from rats fed on selenium-deficient and selenium-supplemented diets. The anti-serum employed in this study was raised against an electrophoretically pure Se-GSH-Px preparation obtained from rat livers by a simplified purification procedure involving separation by high performance liquid chromatography on a hydrophobic interaction column. Different forms of Se-GSH-Px, including apo-protein, cross-reacted with this antiserum and Western blot analysis found no Se-GSH-Px protein present in livers from rats fed on selenium-deficient diets. By contrast, a distinct protein band corresponding to purified Se-GSH-Px was detected in livers from selenium-supplemented animals, a result consistent with the finding that the Se-GSH-Px activity was reduced to undetectable levels in livers of selenium-deficient rats. The in vitro translation experiments, however, indicated not only that mRNA for Se-GSH-Px was present during selenium deficiency but also that its translation products contained 2-3-fold as much immunoprecipitable protein as the products of poly(A) RNA from livers of selenium-supplemented rats. This result suggests that the Se-GSH-Px mRNA may be increased in the selenium-deficient state. Elevated levels of Se-GSH-Px mRNA were directly demonstrated in Northern blot experiments employing cDNA clone pGPX1211 as a probe. A similar increase in Se-GSH-Px mRNA was observed in such other tissues as kidney, testis, brain, and lung tissue, in selenium-deficient states. The present data support the co-translational mechanism for the incorporation of selenium into Se-GSH-Px in rat liver.

Animals

Effect of dietary sodium nitroprusside as a source of cyanide on the selenium status of chicks given diets of varying selenium concentration.

1. The interaction between dietary cyanide, given in the form of sodium nitroprusside (SNP), and selenium has been studied in two experiments with growing chicks from 14 to 38 d of age. 2. In experiment 1, dietary selenium at 10 mg Se/kg reduced growth, food intake and efficiency of utilisation, and increased relative liver size and selenium content. All of these effects were eliminated by the addition of 0.1 g SNP/kg except for liver selenium content, which progressively declined towards control values as SNP was increased to 0.4 g/kg in increments of 0.1 g/kg. At 0.3 g SNP/kg, cyanide toxicity, as judged by decreased growth, reached significance. 3. In experiment 2, similar effects were observed with selenium at 10 mg Se/kg and SNP at 0.3 g/kg, but selenium deficiency was not evident from growth indicators when selenium supplementation of the diet was omitted completely, nor did these indicators suggest that deficiency was induced by cyanide. 4. In both experiments, plasma and liver glutathione peroxidase activity reflected the dietary selenium content. There was an interaction with dietary SNP content. With selenium intake at a toxic level, SNP increased enzyme activity, further evidence of alleviation of selenium toxicity, but when selenium intake was low and normal, SNP decreased activity in liver, an indication that cyanide could induce deficiency. 5. A possible mechanism for alleviation of selenium toxicity is proposed.

Animals

Effect of selenium supplementation on selenium balance in the dependent elderly.

Although trace minerals are necessary constituents of enzymes, dietary requirements of these nutrients for the elderly are unknown. This study measured selenium balance in six dependent elderly men before and after five weeks daily administration of 200 micrograms organically-bound selenium; dietary selenium intake averaged 62.1 +/- 7 micrograms/day during both study periods. Selenium status was assessed not only chemically but also biologically as red cell and platelet glutathione peroxidase activities. Plasma selenium averaged 8.8 +/- 0.8 micrograms% (normal: 10 +/- 2 micrograms %) when intake derived from dietary sources alone and increased during medicinal supplementation to an average of 12.8 +/- 1.9 micrograms %. The rise in plasma selenium was not associated with an increase in red cell or platelet glutathione peroxidase activity. The effect of selenium supplementation on in vivo platelet aggregability was studied by measuring plasma levels of beta-thromboglobulin and platelet factor 4, two proteins secreted concomitant with aggregation. beta-thromboglobulin diminished 7.5 +/- 11.0 ng/ml and platelet factor 7.6 +/- 11.0 ng/ml during selenium supplementation despite no change in platelet glutathione peroxidase activity. These data support the concept that selenium nutritional status should be assessed not only by blood selenium content but also by selenium-dependent enzyme activity or selenium-dependent biologic effect.

Aged

Distribution of selenium in egg white and yolk after feeding natural and synthetic selenium compounds.

Practical diets containing various selenium levels, with and without selenite supplementation, were fed to hens. Eggs were then collected over a 14-day period to determine how quickly changes in dietary selenium affected egg white and yolk selenium. Changes in egg white selenium content were rapid and essentially completed seven days after changing the selenium content of a practical diet. Changes in egg yolk were not yet completed by 14 days. When selenium from practical feedstuffs was fed, the selenium content of dried egg white was about equal to or greater than the selenium content of dried egg yolk. When selenite was fed, the selenium content of dried yolk was higher. Feeding selenomethionine resulted in more selenium in egg white than in egg yolk. Feeding selenocystine resulted in more selenium in egg yolk than egg white, a pattern similar to that from feeding selenite. The data suggest that selenocystine is not incorporated into protein but is metabolized to an inorganic selenium compound.

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