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Type I iodothyronine deiodinase activity after high selenium intake, and relations between selenium and iodine metabolism in rats.

Type I iodothyronine deiodinase (I-D), which catalyzes the production of the thyroid hormone 3,3',5-triiodothyronine from thyroxine, has recently been identified as a selenoenzyme. It is therefore of interest to investigate the relationships between selenium and iodine metabolism. In the livers of Se-deficient rats I-D activity was inhibited; the production of 3,3',5-triiodothyronine and 3,3'-diiodothyronine from added thyroxine was decreased by greater than 95% relative to Se-adequate controls. The hepatic I-D activity was also reduced in rats fed a diet with a low iodine concentration. Unaltered glutathione peroxidase activities in liver and plasma of these rats suggest, however, that with normal Se intake this metabolic pathway of Se is not affected by iodine depletion. When rats were administered 75Se-labeled selenium at levels equal to the amounts ingested from diets with Se concentrations of 0.3 or 2 mg Se/kg, greater Se concentrations were found in the thyroid and liver of the animals receiving the higher dosage. The thyroidal 3,3',5-triiodothyronine and thyroxine concentrations, however, were comparable in rats fed diets with 0.3 mg Se/kg diet as selenite and 2 mg Se/kg as selenite or L-selenomethionine. The measurement of the hepatic I-D and glutathione peroxidase activities in these animals showed that excessive Se supply does not elevate the activities of the two enzymes but might even have the opposite effect. At high Se intake tissue Se concentration cannot therefore be used as indicator of the selenoenzyme activities.

Administration, Oral↗

The selenium requirement for glutathione peroxidase mRNA level is half of the selenium requirement for glutathione peroxidase activity in female rats.

To determine critically the selenium (Se) requirement for weanling female rats, we used glutathione peroxidase (GSH: H2O2 oxidoreductase, EC 1.11.1.9) (GPX) mRNA and a number of other parameters to assess Se status. Rats were fed a basal torulayeast diet (0.007 micrograms Se/g) supplemented with Se as Na2SeO3 in graded levels from 0 to 0.3 micrograms Se/g diet for 32 d (3 rats/group). Selenium supplementation had no effect on growth, showing that the Se requirement for growth is less than 0.007 micrograms Se/g diet, whereas other parameters showed significant increases with Se supplementation. In rats fed the Se-deficient basal diet, liver Se concentration was 4 +/- 0%, plasma GPX activity was 8 +/- 1%, erythrocyte GPX activity was 40 +/- 3%, liver GPX activity was 2 +/- 1%, and liver GPX mRNA levels were 11-17% of the levels in rats fed 0.1 micrograms Se/g diet. Liver Se concentration and GPX activity in plasma, erythrocytes and liver all reached a plateau breakpoint at or near 0.1 micrograms Se/g diet, indicating that the dietary Se requirement for maximal GPX activity in growing female rats is 0.1 micrograms Se/g diet. Liver GPX mRNA levels reached the plateau breakpoint at 0.05 micrograms Se/g diet, showing that the minimum dietary Se requirement for maximal GPX mRNA levels in female rats is half of the Se requirement for maximal GPX activity. This experiment demonstrates that GPX mRNA can be used to determine the dietary Se requirement; the gap between the dietary Se necessary for maximal GPX mRNA and that for maximal GPX activity may represent an evolutionarily derived biological margin of safety.

Analysis of Variance↗

Choice feeding of selenium-deficient laying hens affects diet selection, selenium intake and body weight.

Inadequate selenium (Se) supply often in combination with low vitamin E status causes deficiency symptoms in many species. It is likely that a vague discomfort or sickness is perceived before clear deficiency signs become apparent. We investigated whether Se-deficient hens reduce their Se deficit by selecting a diet containing more selenium when offered two diets with different Se concentrations. A Low-Se diet (0.07 mg Se/kg) was supplemented with Se-enriched yeast (Sel-Plex 50) to produce Medium-Se (0.20 mg Se/kg) and High-Se (1.50 mg Se/kg) diets. Each of two consecutive study parts (I and II) with the same hens and treatments began with a 6-wk baseline period (Medium-Se diet), subsequently followed a 9-wk depletion period (Low-Se diet or Medium-Se diet), then a 6-wk choice feeding period in which two diets with different Se concentrations (Low-Se and Medium-Se, Medium-Se and High-Se, or Low-Se and High-Se) were offered. A control group received the Medium-Se diet throughout the study. Daily Se intake, calculated from daily feed intake, followed similar patterns in both parts of the study, but Se-deficient hens preferred (P < 0.05) the High-Se diet to the Low-Se diet during the first 3 wk of choice feeding only in part I. We conclude that young Se-deficient laying hens reduce their Se deficit if they have a choice between a Low-Se and a High-Se diet by preferentially selecting the High-Se diet, possibly based on learned place preference and/or learned taste aversion to the Low-Se diet, presumably in response to discomfort due to Se-deficiency.

Animals↗

Chemical form and distribution of selenium and sulfur in the selenium hyperaccumulator Astragalus bisulcatus.

In its natural habitat, Astragalus bisulcatus can accumulate up to 0.65% (w/w) selenium (Se) in its shoot dry weight. X-ray absorption spectroscopy has been used to examine the selenium biochemistry of A. bisulcatus. High concentrations of the nonprotein amino acid Se-methylseleno-cysteine (Cys) are present in young leaves of A. bisulcatus, but in more mature leaves, the Se-methylseleno-Cys concentration is lower, and selenate predominates. Seleno-Cys methyltransferase is the enzyme responsible for the biosynthesis of Se-methylseleno-Cys from seleno-Cys and S-methyl-methionine. Seleno-Cys methyltransferase is found to be expressed in A. bisulcatus leaves of all ages, and thus the biosynthesis of Se-methylseleno-Cys in older leaves is limited earlier in the metabolic pathway, probably by an inability to chemically reduce selenate. A comparative study of sulfur (S) and Se in A. bisulcatus using x-ray absorption spectroscopy indicates similar trends for oxidized and reduced Se and S species, but also indicates that the proportions of these differ significantly. These results also indicate that sulfate and selenate reduction are developmentally correlated, and they suggest important differences between S and Se biochemistries.

Astragalus Plant↗

Erythrocyte selenium-75 uptake as a measure of selenium status in weaner sheep, and its relationship to erythrocyte glutathione peroxidase activity.

The relationship between in vitro erythrocyte 75Se uptake (75Se uptake) and erythrocyte glutathione peroxidase (EGSHPx) activity was examined in weaner sheep during periods of selenium depletion and repletion, to determine whether 75Se uptake was better correlated than EGSHPx activity to the development of weaner nutritional myopathy. In the 2 trials conducted, only 3 of 45 Merino wether weaners developed clinical myopathy and histological lesions in skeletal muscles. The 75Se uptake values and EGSHPx activities in these 3 sheep were no different from those in the unaffected sheep. There was a significant negative correlation between 75Se uptake values and EGSHPx activities over the entire period of the trials. It could not be demonstrated that 75Se uptake was any better correlated than EGSHPx activity to the development of nutritional myopathy, and it was concluded that EGSHPx activity indicated selenium status better than 75Se uptake in weaner sheep.

Animals↗

Intramuscular selenium administration in selenium-deficient cattle.

Nine recently weaned Hereford heifers were randomly assigned to a control group (n = 3) or a treatment group (n = 6). The animals were selenium (Se) deficient (mean +/- SD blood Se concentration = 0.024 +/- 0.012 microgram/mL). They were maintained on a selenium-deficient diet, and on day 0 of the study the treatment group was given 0.05 mg Se/kg body weight intramuscularly, while the control group received a placebo. The Se concentration of blood, serum, and urine as well as the glutathione peroxidase (GSH-Px) activity of blood and serum was measured over an 84-day period. Peak blood Se and serum Se concentrations (mean +/- SD) in the treatment group occurred at 5 hours postinjection and were 0.131 +/- 0.028 microgram/mL and 0.154 +/- 0.027 microgram/mL, respectively. The mean blood Se concentration of the treatment group was greater (P < .05) than that of the control group for the first 28 days after injection. The mean serum Se concentration of the treatment group was greater (P < .05) than that of the control group for all times after injection, except for day 56. The mean (+/- SD) blood GSH-Px activity of the treatment group (12.0 +/- 2.3 mU/min/mg hemoglobin) was increased (P < .05) over the control group (2.0 +/- 1.4 mU/min/mg hemoglobin) by day 28 and continued to be greater (P < .05) throughout the 84 day postinjection period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Use of sodium hydroxide treated selenium deficient barley to induce vitamin E and selenium deficiency in yearling cattle.

Selenium deficient barley grown in Northern Ireland was treated with sodium hydroxide to deplete it of vitamin E. Housed cattle fed a complete diet based on this treated barley developed nutritional degenerative myopathy, showing that spontaneous myopathy in yearling cattle can be the result of vitamin E and selenium deficiency alone. The diet used is as effective and cheaper than others presently in use for inducing degenerative myopathy.

Animal Feed↗

Effects of diet and chemical form of selenium on selenium metabolism in sheep.

The effects of diet composition and chemical form of Se on intestinal flow, absorption, and retention of Se were determined in sheep by the balance technique and by disappearance of Se from sites along the gastrointestinal tract with reference to dual-phase digesta markers. Six sheep with ruminal and duodenal cannulas were used in a crossover design with a split-plot arrangement of the Se isotope treatments. Sheep were fed a forage (alfalfa hay)-based (.37 mg Se/kg) or concentrate (barley)-based (.27 mg Se/kg) diet at 90% of ad libitum intake. Selenium stable isotopes (enriched [77Se]yeast, enriched [82Se]selenite) and fluid (Co-EDTA) and particulate (Cr-mordanted fiber) markers were administered simultaneously into the rumen four times daily for 7 d, and total collections of feces and urine were made every 24 h for these and the following 7 d. A larger proportion (51 to 61%) of the Se tracers flowing to the duodenum was associated with the particulate fraction, mainly as bacteria-associated Se, than with the fluid fraction. The [82Se]selenite was more available (P < .05) for absorption and retention than [77Se]yeast, indicating that inorganic chemical forms of Se are as available to the ruminant as organic forms of Se commonly found in feedstuffs. Selenium absorption and retention were greater (P < .05) in sheep receiving the concentrate-based diet than in sheep receiving the forage-based diet. Thus, the availability of Se from inorganic and organic sources in sheep seems to be influenced by diet composition.

Animals↗

Effect of selenium on performance, serum selenium concentration and glutathione peroxidase activity in pigs.

Pigs from sows fed a diet deficient in Se and low in vitamin E were fed a Torula yeast diet supplemented with 100 IU dl-alpha-tocopheryl acetate/kg of diet. Dietary treatments were levels of supplemental Se of 0, .025, .050, .075 or .100 ppm. Some death loss occurred in pigs receiving no supplemental Se at approximately 5 wk of age. Autopsy revealed liver and heart lesions typical of vitamin E-Se deficiency. Selenium supplement had no significant effect on average daily gain, feed intake or gain to feed ratio for the 4-wk experiment. Selenium status of pigs was determined by serum Se concentration and serum glutathione peroxidase (GSH-Px) activity. Serum Se increased linearly (P less than .01) with increasing supplemental Se. Serum GSH-Px activity increased linearly (P less than .01) and quadratically (P less than .05) with increasing supplemental Se. With time, the level of serum Se and GSH-Px activity decreased in unsupplemental pigs, but increased in pigs fed diets supplemented with Se and resulted in significant interactions (P less than .01) between dietary Se level and time on experiment. The correlation between serum Se concentration and GSH-Px activity was .81 (P less than .01).

Animals↗

The influence of dietary selenium levels on blood levels of selenium and glutathione peroxidase activity in the horse.

Twenty mature geldings, averaging 535 kg, were used to determine the influence of dietary selenium (Se) on the blood levels of Se and Se-dependent glutathione peroxidase (SeGSH-Px) activity in the horse. Horses were randomly assigned within breed to four treatments consisting of five horses each and fed a basal diet containing .06 ppm of naturally occurring Se. Diets were supplemented with .05, .10 and .20 ppm Se, as sodium selenite. Blood was drawn for 2 wk before, and for 12 wk following, the inclusion of supplement Se in the diets. Whole blood and plasma Se concentrations and plasma SeGSH-Px activities were determined from all blood samples. Selenium concentrations in plasma and whole blood increased linearly from wk 1 to wk 5 and 6, respectively, in Se-supplemented horses. After these times, no significant changes in Se concentration were observed in Se-supplemented or in unsupplemented horses throughout the remainder of the 12-wk trial. Plasma Se reached plateaus of .10 to .11, .12 to .14, and .13 to .14 micrograms/ml in horses supplemented with .05, .10 and .20 ppm Se, respectively. Whole blood Se reached plateaus of .16 to .18, .19 to .21, and .17 to .18 micrograms/ml in horses supplemented with .05, .10 and .20 ppm Se, respectively. Plasma SeGSH-Px activity was not significantly affected by dietary treatment. Therefore, this enzyme was not a good indicator of dietary Se in these mature horses.

Animals↗

Effects of marginal selenium deficiency and winter protein supplementation on growth, reproduction and selenium status of beef cattle.

Seventy-two Hereford X Simmental cows, averaging 498 kg in body weight and 5.2 yr of age, were used in a 2-yr study to ascertain if selenium (Se)-vitamin E (E) injections and winter protein supplementation would affect growth, reproduction and health of beef cattle maintained year-round on feedstuffs marginally deficient in Se (.03 to .05 mg/kg). Cows received either no injection or a mixture of 30 mg Se (as sodium selenite) and 408 IU E injected subcutaneously beginning 3 to 4 mo prepartum and at 60-d intervals throughout the 2-yr period. Calves born to Se-E treated cows were injected with 5.5 mg Se and 75 IU E/100 kg body weight at 60-d intervals beginning at 1 mo of age. Calves were born between December 30 and February 20 and cows were bred between March 20 and May 20. Cattle grazed pasture (.05 mg Se/kg) that consisted of orchardgrass, bluegrass and white clover during the fall, spring and summer. During winter (December 15 to May 2), cattle were fed corn silage (.03 mg Se/kg) supplemented with either: no protein supplement (control), soybean meal or a urea-corn mixture. Cows and calves receiving Se-E had higher (P less than .01) whole blood glutathione peroxidase (GSH-Px) activity and plasma Se concentrations than controls. Selenium-E injections reduced (P less than .05) calf death losses from 15.3% to 4.2% and slightly increased (P less than .10) adjusted calf weaning weights. Hemoglobin concentrations were higher (P less than .05) in Se-E-injected supplemented calves at 1 mo of age but not at 5 or 7 mo of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of dietary sulfur and selenium concentrations on selenium balance of lactating Holstein cows.

The effects of dietary sulfate and selenium concentrations on selenium balance in dairy cows were investigated. Midlactation Holstein cows (n = 30) were fed diets containing either 0.1 or 0.3 mg of supplemental Se (from sodium selenate)/kg of dry matter and 0, 0.2, or 0.4% added S from a mix of calcium and magnesium sulfate in a factorial arrangement. The experiment lasted 112 d. Dry matter intake was linearly reduced with increasing S, but the effect was greater when 0.3 mg/kg of Se was fed (significant interaction). Treatment effects for yields of milk, milk fat, and milk protein were similar to those for dry matter intake. Increased dietary S linearly reduced plasma Se concentrations. Increasing dietary S linearly reduced apparent (42.7, 33.1, and 30.1%) and estimated true (50.5, 46.0, and 42.3%) Se digestibility. Excretion of Se via feces (1.6 vs. 2.8 mg/d) and urine (0.5 vs. 1.3 mg/d) was higher and output in milk (0.4 vs. 0.3 mg/d) was lower for cows fed 0.3 mg/kg of Se compared with 0.1 mg/kg, but no Se effect was found for estimated true Se digestibility. Dietary S from sulfate reduced Se balance especially when cows were fed diets with less than 0.3 mg of Se/kg of diet dry matter.

Animals↗

The selenium-75-homocholic acid taurine test reevaluated: combined measurement of fecal selenium-75 activity and 3 alpha-hydroxy bile acids in 211 patients.

The recommended reference values for the selenium-75-homocholic acid taurine (75SeHCAT) test, used in the analysis of chronic diarrhea, were evaluated in 211 patients by comparing simultaneous measurements of 3 alpha-hydroxy bile acids and 75Se activity in daily collected stools. An initial evaluation in 11 patients showed that the fecal collection method, which allows inspection and additional analysis of stools, was equivalent to the abdominal retention method. Selenium-75-HCAT whole-body retention half-life (WBR50) was greater than 2.8 days in less than 10% of the patients with bile acid malabsorption and less than 1.7 days in less than 10% of the normals. We recommend that a 75SeHCAT WBR50 less than 1.7 days is abnormal, a WBR50 greater than 2.8 days is normal, and a WBR50 in the range 1.7-2.8 days is equivocal, which was the case in 48% (94/195) of the patients in this study.

Bile Acids and Salts↗

Experimentally induced Staphylococcus aureus mastitis in selenium-deficient and selenium-supplemented dairy cows.

Ten Holstein cows were fed a selenium-deficient (SeD) diet containing 0.04 mg of Se/kg of dry matter for 3 months before and throughout their first lactation. A selenium-supplemented (SeS) group of 10 cows was fed an additional 2 mg of Se/head/d to increase dietary Se concentration of the dry matter to approximately 0.14 mg/kg of body weight. An intracisternal challenge exposure of 40 to 60 colony-forming units (CFU) of Staphylococcus aureus was administered into 1 or 2 quarters of the udder of each trial cow at about the twenty-second week of lactation. Blood Se concentration (micrograms/ml +/- SEM) at the time of challenge exposure was 0.035 +/- 0.002 in SeD and 0.139 +/- 0.006 in SeS cows. Infections were established in 14/16 of the challenge-exposed quarters in SeD and 16/19 of the challenge-exposed quarters in SeS cows. The infection in 1 quarter of each Se group cleared without treatment by the end of the 8-week trial period. Log10 peak bacterial concentrations in milk from infected SeD quarters (5.04 +/- 0.25 CFU/ml) were higher (P less than 0.05) than those of infected SeS quarters (4.40 +/- 0.12 CFU/ml). Log10 peak somatic cell count (SCC) in milk from infected SeD quarters (7.18 +/- 0.08 cells/ml) did not differ from that of SeS quarters (7.17 +/- 0.05 cells/ml). Peak bacterial concentrations were attained sooner (P less than 0.05) in SeD quarters (9.5 +/- 4.0 days) than in SeS quarters (20.7 +/- 3.1 days). Similarly, peak SCC were reached earlier (P less than 0.05) in SeD (4.3 +/- 1.1 days) than in SeS quarters (13.3 +/- 3.8 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selenium supplementation does not alter platelet activation in subjects with normal selenium status.

The effect of Se supplementation on the plasma concentrations of platelet specific proteins, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), was determined in twenty young women with normal selenium (Se) status using a double blind protocol. Selenium supplementation for 4 weeks (150 micrograms/day), did not elevate the initial mean plasma Se level 95 +/- 4 ng/ml above this level, nor did it alter the plasma beta TG/PF4. Moreover, all the other parameters of the body antioxidative status (plasma alpha-tocopherol, retinol and uric acid and whole blood glutathione) measured in this experiment stayed unaltered during the 4-week supplementation period. The results indicate no relationship between Se supplementation and platelet function in subjects with normal Se status.

Adult↗

Effects of selenium and copper administration on blood selenium and copper profile of cattle.

Forty yearling shorthorn heifers were winter-fed barley silage, a diet low in copper and selenium. The animals were divided into 4 groups of 10 animals each. One group was unsupplemented, while other treatments were copper (Cu), selenium (Se), or combined Cu-Se administered by subcutaneous injections. Low Cu and Se concentrations were observed in the blood plasma of the unsupplemented group. The administration of Cu and Se raised the blood plasma Cu and Se concentrations in the heifers. However, Cu or Se administration had no effect on the growth of heifers and there was no interaction between the Se and Cu treatments.

Animals↗

The role of selenium-dependent and selenium-independent glutathione peroxidases in the formation of prostaglandin F2 alpha.

In recent years, growing evidence suggests that glutathione peroxidases (GSH-Pxs), both selenium-dependent GSH-Px (Se-GSH-Px) and selenium-independent GSH-Px (non-Se-GSH-Px) play an important role in the biosynthesis of prostaglandins and leukotrienes and in the regulation of key enzymes associated with the arachidonic acid cascade. The precise nature of their involvement in eicosanoid metabolism, however, is not yet completely understood. In the study reported here, we have systematically determined the catalytic efficiencies of Se-GSH-Px and non-Se-GSH-Px toward prostaglandin (PG) G2 (PGG2) and PGH2. Se-GSH-Px exhibited high catalytic activity for the reduction of PGG2 as indicated by Km and Vmax values of 12 microM and 78 mumol/min/mg, respectively, whereas PGH2 was found to be a poor substrate, an indication that Se-GSH-Px reduces the hydroperoxide moiety but not the endoperoxide moiety of PGG2. The kinetic constants of Se-GSH-Px toward PGG2 were comparable to those determined for such classical substrates as H2O2 and cumene hydroperoxide. In contrast to Se-GSH-Px, non-Se-GSH-Px associated with cationic isozyme II of glutathione S-transferases (GSTs) from sheep lung cytosol was very active in the conversion of PGH2 to PGF2 alpha with a Vmax of 960 nmol/min/mg and a Km of 77 microM. This study shows that PGF2 alpha formation by non-Se-GSH-Px occurred in a GSH-dependent reduction of either PGG2 or PGH2. When PGG2 was used as the substrate for non-Se-GSH-Px, a novel intermediate compound appeared and was later identified by several methods of structural analysis as 15-hydroperoxy PGF2 alpha. Thus, the reductive cleavage of the endoperoxide occurs faster than the 15-hydroperoxide reduction allowing 15-hydroperoxy PGF2 alpha to accumulate briefly. A study of GSTs from several different tissues and species indicated that the transformation of PG endoperoxides to PGF2 alpha is catalyzed specifically by GST isozymes, which contain Ya size subunits. This specificity of GST isozymes in PG biosynthesis, coupled with their tissue-specific expression, may be a mechanism by which the body modulates the type of PGs produced in these tissues. Also, these results suggest a possible interaction of Se-GSH-Px and non-Se-GSH-Px in the biosynthesis of PGF2 alpha.

Animals↗

Selenium levels in whole blood of Finnish volunteers before and during organic and inorganic selenium supplementation.

High selenium barley biscuits containing 1 mumol (70 micrograms) organic Se were administered to healthy male volunteers for 5 weeks at doses of 2.1 mumol Se (group A) or 6.4 mumol (group B). In addition, 2 mg Na-selenate capsules (5.4 mumol Se) were given to two other groups at daily doses of 2 mg (group C) or 8 mg (group D). Groups A, B and C each comprised eight healthy men and group D eight healthy women and three men. The initial median concentration of whole blood selenium (B-Se for groups A, B and C were 1.0-1.1 mumol/l (range 0.7-1.7) and for group D 1.3 mumol/l (range 0.9-1.8). In 1-2 weeks time the B-Se concentrations rose to 1.6 mumol/l for groups A and C, to 1.8 mumol/l for group B, and to 2.2 mumol/l for group D. There was no decrease 1 week after the Se intake ceased. As expected, the level of B-Se increased more (in relation to dose) in those given organic Se than in those given inorganic Se. Groups A, B and C, however, had rather moderate increases. The daily dose required to raise the B-Se of Finns up to the North American level (2.2 mumol/l) was as high as 8 mg Na-selenate (21.5 mumol or 1700 micrograms Se), but the dose of organic Se which would be required to achieve this level is not yet known.

Female↗