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An examination of the selenium nutrition of sheep in Victoria.

The selenium nutrition of sheep throughout Victoria was assessed by a survey of the blood glutathione peroxidase activity in 708 flocks. It was shown that the blood glutathione peroxidase activity in sheep had a seasonal variation with lowest levels in the spring. The enzyme activity was correlated with the blood selenium concentration. Areas where blood selenium was less than 0.03 micrograms/ml in spring were defined. Sheep with low selenium nutrition were grazing pastures in the high rainfall areas on acid soils, particularly those derived from granite. Selenium concentrations in pasture samples examined were greater than 0.02 mg/kg, and it was found that superphosphate application had no significant effect on the selenium content of pasture. However, management practices such as high stocking rates and rates of application of superphosphate to pasture were associated with low blood glutathione peroxidase activities in sheep. It was concluded that the selenium nutrition of most of the sheep flocks in Victoria is adequate, and that the deficient areas are localised. There seems little requirement for supplementation of adult sheep. As the delayed type of white muscle disease in spring lambs appears to be the main selenium-responsive disorder, direct supplementation of lambs in the low selenium areas would be the most effective method of ensuring adequate selenium nutrition.

Animals↗

Selenium in human lactation.

The primary factor determining selenium concentration in human milk is the maternal selenium intake. A significant correlation between selenium in human milk and maternal selenium intake has been reviewed in papers from different regions of the world. Infants fed human milk have higher selenium intake than those fed commercially available formula milk or baby foods. Selenium compounds found in breast milk seem to be more biologically available for infant nutrition than those in formulas. Increased requirements of selenium have been observed in pregnant and lactating women. Supplementation of lactating and pregnant women with different selenium compounds has been assayed, and selenium supplementation of soil and cows has been used to increase the selenium status of children fed infant formula made from cow's milk.

Biological Availability↗

Selenium biochemistry.

The toxicity of selenium to animals and plants has been known and extensively documented since the 1930's, but it is only during the past 15 years that selenium has also been shown to be an essential micronutrient for animals and bacteria. Very little is known about the specific role or roles of selenium and, to date, there are only three enzyme-catalyzed reactions that have been shown to require the participation of a selenium-containing protein. These are the reactions catalyzed by (i) formate dehydrogenase of bacteria, (ii) glycine reductase of clostridia, and (iii) glutathione peroxidase of erythrocytes. The common denominator of these selenium-dependent processes is that they are all oxidation-reduction reactions. A fourth selenoprotein has been isolated from skeletal muscle of sheep but its catalytic function has not been identified. The form in which selenium occurs in these selenoproteins is unknown. The selenoprotein of clostridial glycine reductase contains selenium in a covalently bound form. Studies in progress indicate that this may be an organoselenium compound not previously detected in nature. Identification of the chemical nature of selenium in proteins participating in electron transport processes should enable us to determine its specific role and to understand the basic defects in certain cardiac and skeletal muscle degenerative diseases which are selenium-deficiency syndromes. The greater availability and ease of isolation of the selenoprotein of the bacterial glycine reductase system makes this the biological material of choice for studies on the mechanism of action of selenium. An added attractive feature of this system is that it can conserve the energy made available by the reductive deamination of glycine in a biologically useful form by synthesizing ATP.

Adenosine Triphosphate↗

Protective effect of selenium on lung cancer in smelter workers.

A possible protective effect of selenium against lung cancer has been indicated in recent studies. Workers in copper smelters are exposed to a combination of airborne selenium and carcinogens. In this study lung tissue concentrations of selenium, antimony, arsenic, cadmium, chromium, cobalt, lanthanum, and lead from 76 dead copper smelter workers were compared with those of 15 controls from a rural area and 10 controls from an urban area. The mean exposure time for the dead workers was 31.2 years, and the mean retirement time after the end of exposure 7.2 years. Lung cancer appeared in the workers with the lowest selenium lung tissue levels (selenium median value 71 micrograms/kg wet weight), as compared with both the controls (rural group, median value 110; urban group, median value 136) and other causes of death among the workers (median value 158). The quotient between the metals and selenium was used for comparison: a high quotient indicating a low protective effect of selenium and vice versa. The median values of the quotients between antimony, arsenic, cadmium, lanthanum, lead, chromium, and cobalt versus selenium were all numerically higher among the cases of lung cancer, the first five significantly higher (p less than 0.05) in 28 of the 35 comparisons between the lung cancer group and all other groups of smelter workers and controls. The different lung metal concentrations for each person were weighted according to their carcinogenic potency (Crx4 + Asx3 + Cdx2 + Sbx1 + Cox1 + Lax1 + Pbx1) against their corresponding selenium concentrations. From these calculations the protective effect of selenium was even more pronounced.

Aged↗

Effect of selenium-deficient diet in experimental glomerular disease.

We examined the effect of a selenium-deficient diet on two experimental models of glomerular disease, the puromycin aminonucleoside (PAN)-induced nephrotic syndrome, a model of minimal change disease, and passive Heymann nephritis, a complement-dependent and neutrophil-independent model that resembles membranous nephropathy. The specific activity of selenium-dependent glutathione peroxidase was markedly reduced in the liver, the kidney cortex, and in glomeruli in weanling male Sprague-Dawley rats placed on a selenium-deficient diet for 6 wk compared with rats fed a selenium-replete diet, with no significant differences in the specific activities of superoxide dismutase or catalase. PAN-injected selenium-deficient rats had a marked and significantly greater proteinuria throughout the course of the experiment compared with PAN-injected selenium-replete rats with no significant histological differences. In the passive Heymann nephritis model induced by injecting anti-Fx1A immunoglobulin G, rats fed a selenium-deficient diet had significantly higher urinary protein (day 5: 91 +/- 16 mg/24 h, n = 10) compared with rats fed a selenium-replete diet (52 +/- 5 mg/24 h, n = 11) with no differences in the amount of antibody deposited in the kidney. The most likely explanation for the effect of a selenium-deficient diet is that selenium deficiency resulted in a marked reduction of glutathione peroxidase, thus indicating an important role of glutathione peroxidase in these models of glomerular injury.

Animals↗

The effect of supplementation with selenium and vitamin E in psoriasis.

Since reduced concentrations of selenium in whole blood, plasma and white cells had previously been observed in psoriasis, 69 patients were supplemented daily with either 600 micrograms of selenium-enriched yeast, 600 micrograms of selenium-enriched yeast plus 600 IU of vitamin E or a placebo for 12 weeks. Before supplementation, the patients' mean concentrations of selenium in whole blood and plasma were reduced compared with those of matched healthy controls but their red cell glutathione peroxidase (GSH-Px) activity was normal. After 12 weeks supplementation the patients' mean whole blood, plasma and platelet selenium concentrations, platelet GSH-Px activity and plasma vitamin E concentration had risen significantly from the baseline values but their mean skin selenium concentration and red cell GSH-Px activity remained unchanged. The mean white cell selenium concentration rose only in the group receiving selenium alone. Neither supplementation regimen reduced the severity of psoriasis or produced side-effects. The increase in platelet GSH-Px activity suggests that the supplements were bioavailable and that the patients' selenium status may have been reduced prior to supplementation. The failure of the selenium content of the skin to increase may explain why the patients' psoriasis remained unchanged during supplementation.

Adult↗

Low blood selenium levels in patients with cystic fibrosis compared to controls and healthy adults.

Frank clinical selenium deficiency has been described in cystic fibrosis (CF), and a relative deficiency has been proposed as contributing to the pathogenesis of the disease. Because of these possibilities, we investigated the relationship between overall nutritional status in CF with measures of selenium nutriture. Fifteen stable outpatients with CF (group I) were compared to 13 age-matched controls (group II) and 27 healthy adults (group III). Whole blood, plasma, and red blood cell selenium levels were reduced by 31%, 29%, and 33%, respectively, in CF patients vs controls (all p less than 0.001). In addition, both groups I and II showed significantly lower blood selenium levels than healthy adults (p less than 0.005). Nutritional assessment revealed CF patients to be undernourished, with significant decreases in serum albumin (p less than 0.025), weight-for-height deficit (p less than 0.01), and weight-for-age (p less than 0.025) vs controls. However, only the triceps skinfold (TSF) measurement correlated significantly with selenium status (r = 0.56: p less than 0.05 for whole blood selenium vs TSF). We conclude, based on the magnitude of decrement in blood selenium, that it is unlikely that selenium plays a significant primary pathogenic role in cystic fibrosis. However, these patients are at high risk for developing clinical selenium deficiencies. The measurement of blood selenium levels using appropriate age-matched normal standards should be mandatory in all CF patients with malnutrition, or in those requiring parenteral nutritional support.

Adolescent↗

Placental 5-deiodinase activity and fetal thyroid hormone economy are unaffected by selenium deficiency in the rat.

In adult male rats, selenium deficiency results in a near complete loss in the selenoprotein 5'-deiodinase in the liver, resulting in decreased peripheral deiodination of thyroxine (T4) and increased serum T4 concentrations. Serum 3,5,3'-triiodothyronine concentrations are normal or slightly decreased, and serum 3,3',5'-triiodothyronine concentrations are normal or slightly increased in selenium-deficient rats. We now report the effects of selenium deficiency on maternal and fetal thyroid hormone economy and on placental 5-deiodinase activity in the rat. Weanling female rats were fed either a selenium-deficient or selenium-supplemented diet for 4 wk before mating and then throughout gestation. Rats were killed at 21 d of gestation. Selenium deficiency was confirmed by a 95 and 94% decrease in glutathione peroxidase and a 84 and 56% decrease in liver type I outer ring 5' deiodinase activity in the mother and the fetus, respectively. In contrast to the increase in circulating T4 observed in selenium-deficient male and nonpregnant female adult rats, serum T4 was not affected by selenium deficiency in pregnant rats, but there was a 3-fold increase in serum 3,3',5'-triiodothyronine concentrations associated with a 70% decrease in maternal brain type II outer ring 5' deiodinase activity. Maternal serum 3,5,3'-triiodothyronine concentrations were decreased by 21%. Placental 5-deiodinase activity was unaffected by selenium deficiency. In the fetus, serum T4, 3,3',5'-triiodothyronine, and TSH concentrations were not affected by selenium deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution and chemical form of selenium in mice after administration of selenocystine.

To elucidate the relationship between chemical forms of selenium in tissues and subacute liver damage induced by selenocystine (T. Hasegawa et al., Arch. Toxicol., 68, 91 (1994)), the distribution and chemical form of selenium were investigated in ICR male mice treated with the chemical orally (50 mg/kg) and intravenously (5 mg/kg). The time-distribution of selenium in plasma, erythrocytes and liver after separate administration varied. However, Sephadex G-150 chromatograms of plasma, and stroma-free hemolysate from mice treated orally or intravenously with selenocystine, revealed that selenium exists mainly in the albumin and hemoglobin fractions, respectively, and is neither route- or time-dependent. Sephadex G-150 chromatograms of liver cytosol of the animals 1 h after oral administration or 1 and 6 h after intravenous administration showed two selenium-containing fractions, void volume and a low-molecular fraction (Kav = 0.85); 6 h after oral treatment, however, animals had an additional high-molecular fraction (Kav = 0.45). Levels of acid-volatile selenium and dialyzable selenium in the fraction with a Kav value of 0.45 were similar, being 31.2% and 30.3%, respectively. No acid-volatile selenium was recognized in the non-dialyzable high-molecular fraction. The present study demonstrated that when selenocystine is administered orally to mice, the selenium which produces acid-volatile selenium by acidification may bind to protein sulfhydryl groups in the liver cytosol; this was not seen in the case of intravenous administration.

Administration, Oral↗

Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia.

Although the importance of selenium for bone metabolism is unknown, some clinical conditions such as Kashin-Beck osteoarthropathy have been associated with selenium deficiency. Although selenium deficiency induces growth retardation in rats, it has not been established whether this growth inhibition is associated with changes in bone metabolism. We investigated the effect of selenium deficiency on bone metabolism in growing male rats fed a selenium-deficient diet for two generations (Se-). In Se- rats, erythrocyte glutathione peroxidase activity and plasma selenium concentration were strongly reduced compared with pair-fed selenium-adequate rats (Se+). Weight and tail length were reduced by 31% and 13% in the Se- rats, respectively (p < 0.001). The Se- diet was associated with a 68% reduction of pituitary growth hormone (GH; p = 0.01) and a 50% reduction of plasma insulin-like growth factor I (IGF-I; p < 0.001). Plasma calcium was lower and urinary calcium concentration was greater in Se- rats. This group had a 2-fold increase in parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in plasma. Plasma osteocalcin and urinary deoxypyridoline were reduced by 25% and 57% in the Se- rats (p < 0.001). Selenium deficiency resulted in a 23% and 21% reduction in bone mineral density (BMD) of the femur and tibia (p < 0.001) and this effect persisted after adjustment for weight in a linear regression model. A 43% reduction in trabecular bone volume of the femoral metaphysis (p < 0.001) was found in Se- rats. This experimental study shows that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and osteopenia in second-generation selenium-deficient rats.

Amino Acids↗

Generational differences in selenium status of women.

In this cross-sectional study of three generations of women, daughters (19-26 yr), mothers (40-58 yr) and maternal grandmothers (67-84 yr) from the same 10 families in central Ohio were studied to determine the effect of life-cycle differences, including estrogen status, on selenium status. Plasma and red blood cell (RBC) selenium and glutathione peroxidase (GPx) activities were determined and typical dietary selenium intakes were calculated from food-frequency questionnaires. Selenium status was lowest in the oldest generation. Plasma selenium of daughters and grandmothers were significantly lower than those of mothers, and plasma GPx and RBC selenium of grandmothers were also lower than those of the mothers. A positive correlation (r = 0.42, p < 0.04) was found between plasma estrogen and plasma selenium concentrations. Selenium intakes of all groups were adequate and no differences in selenium intakes were found among groups. The results of this study indicate that selenium status fluctuates during the female life cycle and is related to estrogen status.

Adult↗

Phytoremediation of selenium-contaminated soils and waters: fundamentals and future prospects.

Interest in selenium pollution and remediation technology has escalated during the past two decades. Although not known to be essential for plants, selenium is an essential micronutrient for humans and animals, having important benefits for their nutrition. At high concentrations, however, selenium becomes toxic to animals and humans. A major selenium controversy in the 1980s emerged in California at the Kesterson National Wildlife Refuge; hence, scientists, environmental regulators, politicians, and the general public in the United States became aware of selenium's potential as an environmental contaminant. Consequently, extensive research has been conducted in the western United States, and a vast amount of financial resources have been allocated to develop management strategies and remediation technologies for reducing the impact of naturally occurring selenium on the biological environment. A plant-based technology, defined as 'phytoremediation', has received increasing recognition as a low-cost, environmentally friendly approach for managing the toxic effects of selenium. Plants have the ability to absorb and sequester selenium and to convert inorganic selenium to volatile forms of organic compounds that are released harmlessly into the atmosphere. The present review summarizes recent research findings and information about strategies on using phytoremediation systems to detoxify selenium-contaminated soils and waters in natural and agricultural ecosystems.

Antioxidants↗

Selenium-based pharmacological agents: an update.

The biochemistry and pharmacology of selenium is a subject of intense current interest, particularly from the viewpoint of public health. Selenium, long recognised as a dietary antioxidant, is now known to be an essential component of the active sites of several enzymes, including glutathione peroxidase and thioredoxin reductase, which catalyse reactions essential to the protection of cellular components against oxidative and free radical damage. A low concentration of selenium in plasma has been identified as a risk factor for several diseases, including cancer, cardiovascular disease, osteoarthritis and AIDS, and several large-scale selenium supplementation human trials are now underway. Evidence is emerging that, at least in the case of cancer, the antitumorigenic effect of selenium supplementation arises at least in part from enhanced production of specific selenium-containing metabolites, not just from maximal expression of selenoenzymes. Therefore a number of novel pharmaceutical agents which are selenium-based or which target specific aspects of selenium metabolism are under development. Among these are orally-active antihypertensive agents, anticancer, antiviral, immunosuppressive and antimicrobial agents, and organoselenium compounds which reduce oxidative tissue damage and edema. It can be anticipated that as our understanding of the basic biology and biochemistry of selenium increases, the coming years will bring further development of new selenium-based pharmaceutical agents with therapeutic potential toward a variety of human diseases.

Animals↗

Selenoenzyme expression in thyroid and liver of second generation selenium- and iodine-deficient rats.

The stimulation of thyroid hormone synthesis in iodine deficiency may increase the requirement for the selenoproteins which are involved in thyroid hormone synthesis in the thyroid gland. Selenoenzyme activity and expression were investigated in the thyroid and liver of second generation selenium-and/or iodine-deficient rats. Selenium deficiency caused substantial decreases in hepatic selenium-containing type I iodothyronine deiodinase (ID-I) and cytosolic glutathione peroxidase (cGSHPx) activities and mRNA abundances, but phospholipid hydroperoxide glutathione peroxidase (phGSHPx) activity was only 55% of selenium-supplemented control levels, despite the absence of change in its mRNA abundance. Selenoenzyme mRNA concentrations were maintained at control levels in thyroid glands from the selenium-deficient rat pups. Despite this, a differential effect was observed in selenoenzyme activities: ID-I activity was decreased to 61%, cGSHPx activity to 45% and phGSHPx to 29% of that in selenium-adequate controls. In iodine-deficient thyroid glands, mRNA levels were increased 2.2, 5.0 and 2.8 times for ID-I, cGSHPx and phGSHPx respectively. ID-I and cGSHPx enzyme activities were also increased but the activity of phGSHPx was decreased despite the high mRNA abundance. Thyroid selenoprotein mRNA levels were also increased in combined selenium and iodine deficiency but again there were differential effects on enzyme activities, with ID-I activity increased, cGSHPx unchanged and phGSHPx decreased. Thus, iodine deficiency may produce an oxidant stress on the thyroid gland, increasing the requirement for selenium to maintain selenoenzyme activity. When dietary supplies of selenium are limiting, thyroid selenoprotein mRNA levels are increased to compensate for overall lack of the micronutrient. Furthermore, there is a preferential supply of available selenium to ID-I and cGSHPx to allow maintenance of thyroid function.

Aging↗

Vitamin E and selenium for reproduction of the dairy cow.

Selenium injections and oral vitamin E supplementation prepartum were related to incidence of retained placenta, metritis, and cystic ovaries in a 2 X 2 factorial experiment. Groups were: 1) selenium and vitamin E, 2) vitamin E, 3) selenium, and 4) control. Incidence of retained placenta was 17.5% in cows of groups 2, 3, and 4, whereas it was reduced to 0% in cows receiving both selenium and vitamin E. Incidence of metritis was 60% for cows injected with selenium and 84% for those not receiving selenium. Cystic ovaries were diagnosed in 19% of cows injected with selenium, and incidence was 47% for cows not treated with selenium. Supplementation of vitamin E was required in addition to selenium for prevention of retained placenta of cows fed stored ensiled forage, and prepartum selenium injections were effective for reducing the incidence of metritis and cystic ovaries during the early postpartum period.

Animals↗

The effect of dietary selenium level on lead toxicity in the Japanese quail.

Previous studies (Parizek et al., 1969) have shown significant interactions between selenium and certain heavy metals, particularly mercury and cadmium. Since these elements have an affinity for sulfhydryl groups, it was proposed that a similar interaction might exist with lead. In an initial experiment, adult quail hens were given diets supplemented with 0 and 1 p.p.m. selenium and 0, 500 and 1000 p.p.m. lead in a 2 X 3 factorial arrangement. After 32 days of feeding, body weight, liver weight and egg production decreased in birds fed lead while kidney weights increased. Highly significant decreases in red blood cell delta-aminolevulinic acid dehydratase (RBC-ALAD) activity occurred when lead was added to the diet. Control RBC-ALAD activity was 1337 versus 105, 91, 156 and 110 nmol. porphobilogen produced per ml. of erythrocyte per hour (nmol. PBG/ml. RBC/hr.) for the 500, 1000, 500 plus selenium and 1000 plus groups, respectively. After 85 days of feeding lead to male birds in a second study, selenium appeared to have variable effects on the concentration of lead in liver, kidney and tibia. Selenium supplementation to lead diets resulted in significantly increased levels of lead in kidney tissue while little or no effects were observed on liver or tibia lead levels. RBC-ALAD activity was significantly reduced with lead supplementation and no effect of selenium addition was observed. Electrophoretic gels of serum from birds fed lead containing diets showed increased protein bands in the transferrin and globulin regions regardless of the presence of 1 p.p.m. selenium. A third study was conducted to determine the effects of supplementing an isolated soy protein diet with 0 and 1 p.p.m. selenium and 0 and 3000 p.p.m. lead. Selenium supplementation improved body weights over controls while lead additions caused reduced egg production and ALAD activity. Lead feeding increased tibia/body weight ratios and lead concentrations in liver, kidney and tibia. No significant interaction between lead and selenium was observed.

Animals↗

Influence of selenium, vitamin E, and ethoxyquin on lipid peroxidation in muscle tissues from fowl during low temperature storage.

The influences of various factors which affect the selenium-vitamin E status of laying hens on lipid peroxidation in muscle tissues during low temperature storage were studied. Laying hens from 32 to 56 weeks of age were fed low selenium and low vitamin E practical diets supplemented with different levels of Na2SeO3, d1-alpha-tocopherol acetate, ethoxyquin, and/or peroxidized corn oil. Vitamin E status as indicated by plasma vitamin E activity was improved by supplements of vitamin E, selenium, or ethoxyquin. Selenium status as indicated by plasma selenium-dependent glutathione peroxidase activity was improved by selenium supplementation. Incorporation of peroxidized corn oil into diets did not depress plasma vitamin E but increased plasma glutathione peroxidase when those diets contained supplemental selenium. Lipid peroxidation as indicated by the 2-thiobarbituric acid (TBA) method in muscle samples held at -20 C for up to 270 days was reduced by dietary selenium in M. pectoralis when corn oil was fed. Supplemental vitamin E or ethoxyquin reduced TBA values developed in M. gastrocnemius. Results indicate that dietary selenium and other factors affecting selenium status may be useful in retarding the development of oxidative rancidity in frozen poultry products.

Animals↗

Trends in selenium status of South Australians.

OBJECTIVE: To assess trends in selenium status in South Australians from 1977 to 2002. DESIGN: Six cross-sectional surveys. PARTICIPANTS: 117 participants in 1977, 30 in 1979, 96 and 103 (separate surveys) in 1987, 200 in 1988, and 288 volunteer blood donors in 2002. A total of 834 healthy Australian adults (mean age, 42 years [range, 17-71 years]; 445 were male). MAIN OUTCOME MEASURES: Plasma and whole blood selenium concentrations. RESULTS: The 2002 survey yielded a mean plasma selenium concentration of 103 micro g/L (SE, 0.65), which reached the estimated nutritional adequacy level of 100 micro g/L plasma selenium. Mean whole blood selenium declined 20% from the 1977 and 1979 surveys (mean whole blood selenium concentration, 153 micro g/L) to the 1987, 1988 and 2002 surveys (mean whole blood selenium concentration, 122 micro g/L). Plasma selenium was higher in men (P = 0.01), and increased with age in both men and women (P = 0.008). CONCLUSIONS: In healthy South Australian adults sampled from 1977 to 2002, whole blood and plasma selenium concentrations were above those reported for most other countries and in most previous Australian studies, notwithstanding an apparent decline in selenium status from the late 1970s to the late 1980s.

Adolescent↗