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PubMed1991

The role of selenium in thyroid hormone metabolism.

In animals, decreases in selenium-containing glutathione peroxidase activity and the resultant impairment of peroxide metabolism can account for many, but not all of the biochemical and clinical changes caused by selenium deficiency. Recently, however, type I iodothyronine 5'-deiodinase has also been shown to be a selenium-containing enzyme. This explains the impairment of thyroid hormone metabolism caused by selenium deficiency in animals with a normal vitamin E status. Since iodothyronine 5'-deiodinases are essential for the production of the active thyroid hormone 3,5,3'-triiodothyronine, some of the consequences of selenium deficiency may result from thyroid changes rather than inability to metabolise peroxides. In particular, the impaired thyroid hormone metabolism may be responsible for decreased growth and resistance to cold stress in selenium-deficient animals. A further consequence of the role of selenium in thyroid hormone metabolism is the exacerbation of some of the thyroid changes in iodine deficiency by a concurrent selenium deficiency. Selenium status may therefore have a major influence on the outcome of iodine deficiency in both human and animal populations.

Animals↗

PubMed2005

Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis.

Selenoprotein P is an abundant extracellular glycoprotein that is rich in selenocysteine. It has two domains with respect to selenium content. The N-terminal domain of the rat protein contains one selenocysteine residue in a UxxC redox motif. This domain also has a pH-sensitive heparin-binding site and two histidine-rich amino acid stretches. The smaller C-terminal domain contains nine selenocysteine and ten cysteine residues. Four isoforms of selenoprotein P are present in rat plasma. They share the same N terminus and amino acid sequence. One isoform is full length and the three others terminate at the positions of the second, third, and seventh selenocysteine residues. Selenoprotein P turns over rapidly in rat plasma with the consequence that approximately 25% of the amount of whole-body selenium passes through it each day. Evidence supports functions of the protein in selenium homeostasis and oxidant defense. Selenoprotein P knockout mice have very low selenium concentrations in the brain, the testis, and the fetus, with severe pathophysiological consequences in each tissue. In addition, those mice waste moderate amounts of selenium in the urine. Selenoprotein P binds to endothelial cells in the rat, and plasma levels of the protein correlate with prevention of diquat-induced lipid peroxidation and hepatic endothelial cell injury. The mechanisms of these apparent functions remain speculative and much work on the mechanism of selenoprotein P function lies ahead. Measurement of selenoprotein P in human plasma has shown that it is depressed by selenium deficiency and by cirrhosis. Selenium supplementation of selenium-deficient human subjects showed that glutathione peroxidase activity was optimized before selenoprotein P concentration was optimized, indicating that plasma selenoprotein P is the better index of human selenium nutritional status.

Amino Acid Sequence↗

PubMed2000

Selenium depletion in hemodialysis patients treated with polysulfone membranes.

BACKGROUND/AIMS: Epidemiological, animal and human studies have indicated that selenium deficiency is a risk factor for death from malignant diseases. The mechanisms that could modify selenium status may, therefore, be of particular interest in hemodialysis patients, considering their high cancer mortality rates. We aimed at evaluating the effect of hemodialysis with polysulfone membranes on selenium status. METHODS: Twenty- eight chronically dialyzed patients and 32 age-matched healthy controls were enrolled in the study. Serum and dialysis fluid selenium concentrations, serum total protein, and hemoglobin concentrations and serum glutathione peroxidase activity were determined before and after the hemodialysis procedure. RESULTS: The (mean +/- SD) serum selenium and total protein concentrations and glutathione peroxidase activities were significantly (p < 0.05) higher in healthy controls (75.9 +/- 8.3 microg/l, 78 +/- 6 g/l, and 23.8 +/- 4.8 mU/20 microl, respectively) than in the patients. There was no significant difference between serum selenium concentration before (63.6 +/- 11. 6 microg/l) and after (64.4 +/- 11.4 microg/l) hemodialysis sessions, although hemoglobin and total serum protein concentrations and serum glutathione peroxidase activities increased (from 98.5 +/- 1.3 to 114.8 +/- 1.5 g/l, from 64 +/- 8 to 71 +/- 9 g/l, and from 16.8 +/- 1.8 to 18.9 +/- 1.9 mU/20 microl, respectively) significantly (p < 0.05) during hemodialysis, indicating hemoconcentration. The selenium concentration doubled, and protein appeared in the dialysates during dialysis session. The correlation of the selenium concentrations with the protein concentrations in the dialysate is significant (p < 0.01) with a Spearman R value of 0.97. CONCLUSION: The results of the present study suggest that selenium is lost through the pores of polysulfone membranes during hemodialysis which is associated with their protein permeability.

Adult↗

PubMed2002

Maternal selenium nutrition and neonatal immune system development.

We evaluated the impact of dietary selenium intake on neonatal immune cell differentiation and function. A low selenium intake during pregnancy and lactation produced reductions in maternal plasma selenium (33%, p = 0.0001), milk selenium (36%, p = 0.001), and corresponding neonatal plasma selenium (47%, p = 0.008). Thymocytes from neonates receiving low-selenium milk showed an impaired activation in vitro (p = 0.001). The percentages of CD8 cytotoxic T cells (p = 0.03), CD2 T cells (p = 0.09), panB cells ( = 0.02), and natural killer cells (p = 0.07) were all decreased in neonates nursed by mothers fed a low-selenium diet. The results indicate that maternal selenium intake impacts neonatal selenium status which in turn influences the neonatal immune system development.

Animals↗

PubMed2003

Selenium is depleted in Crohn's disease on enteral nutrition.

BACKGROUND/AIMS: [corrected] Selenium is an important trace element and its deficiency has been reported to be associated with cardiomyopathy or gastrointestinal cancer. The aim of this study is to clarify the selenium status in Crohn's disease (CD) on enteral nutrition. METHODS: We measured serum selenium concentrations in 53 patients with CD and compared them with those in 21 healthy controls. Twenty-nine patients were under the treatment by enteral nutrition (EN group), and the remaining 24 patients were free from formulated enteral nutrition (non-EN group). RESULTS: While the serum selenium concentration in the non-EN group was not decreased when compared to controls, the value in the EN group was significantly lower than those in the non-EN group and in controls. Clinical manifestations of selenium deficiency were found in a patient on exclusive enteral nutrition. In the EN group, the serum selenium concentration showed an inverse correlation with the duration and the daily dose of enteral nutrition. In the non-EN group, the serum selenium concentrations were inversely correlated with the Crohn's disease activity index. CONCLUSION: These findings suggest that patients with CD on enteral nutrition are at risk for selenium deficiency and that even patients without enteral nutrition may develop selenium deficiency at the active phase of the disease.

Adolescent↗

PubMedDate not supplied

Prediction of whole blood selenium levels in patients on long-term parenteral nutrition.

In an attempt to define clinical variables which might predict the whole blood selenium level prior to supplementation, whole blood selenium levels were determined in 21 home parenteral nutrition patients who were not receiving selenium supplementation. These levels were examined for possible correlations by single and multivariant analysis with the following clinical parameters: age at initiation of home parenteral nutrition, months of home parenteral nutrition received, hematocrit, albumin, estimated length of remaining small bowel, kilocalories per kilogram actual body weight infused per day, grams protein per kilogram actual body weight infused per day, and multiple of ideal body weight. Of all the combinations of variables examined, the best correlation obtained was between whole blood selenium levels and the total kilocalories per kilogram body weight per day delivered intravenously (r = -0.89, p less than 0.001). A statistically significant correlation (r = -0.67, p less than 0.01) was also observed between selenium levels and the grams protein per kilogram actual body weight infused per day. However, inclusion of this or additional variables did not increase the predictive value of the equation describing whole blood selenium levels as a function of the calories delivered. The implication of this study is that patients requiring more intensive nutritional support develop lower selenium levels during the course of treatment. Despite these correlations, no single clinical parameter or combination of parameters, however, was of sufficient predictive value to preclude laboratory determination of whole blood selenium values in deciding which patients might benefit from selenium supplementation.

Adolescent↗

PubMedDate not supplied

Selenium deficiency in the acquired immunodeficiency syndrome.

Severe protein-calorie malnutrition is common in patients with AIDS (acquired immunodeficiency syndrome). These nutritional deficits are likely to further impair immune responses and other organ functions vital for recovery from serious infectious diseases. Since selenium deficiency is known to be associated with oral candidiasis and abnormal phagocytic function in animals and depressed helper T-cell numbers in man, we evaluated both selenium status and other nutritional parameters in 12 patients with AIDS compared to 27 healthy controls. Selenium was measured by a spectrofluorometric method. The mean (+/- SD) plasma selenium level in AIDS was 0.043 +/- 0.01 microgram/ml vs 0.095 +/- 0.016 microgram/ml in controls (p less than 0.001). Whole blood selenium and red blood cell selenium levels were also significantly reduced in AIDS (p less than 0.005). The mean weight loss in AIDS patients was 35.5 +/- 21.2 pounds. Serum albumin was significantly (p less than 0.01) lower in AIDS patients compared to controls. A good correlation between serum albumin and plasma selenium was noted (r = 0.77; p less than 0.001). We conclude that selenium deficiency is a common component of the malnutrition seen in AIDS patients. Therefore, aggressive nutritional support, including attention to selenium status, should be considered an integral part of the therapy of AIDS patients.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Serum concentration of selenium in healthy individuals living in Tehran.

OBJECTIVE: To investigate whether daily diet provides adequate selenium intake in healthy men and women living in Tehran, Iran. METHOD: Serum level of selenium was determined in 184 healthy individuals of both genders. The samples were divided into two age groups, adults and children, for analysis. The serum level of selenium was determined using hydride generation and flame atomic absorption spectroscopy. RESULTS: The mean and standard deviation of serum selenium levels in children (1-16 years) was 84.3 +/- 11 microg/l and there was no significant difference between genders in this group. In adults (older than 16 years) the mean serum selenium level was 100.6 +/- 13 SD microg/l; among women the mean was 93.9 +/- 14 SD microg/l and among men it was 102.2 +/- 12 SD microg/l. The mean selenium level in men was higher than in women and data analysis showed a significant difference between them (p < 0.005). There was also a positive correlation between higher selenium serum concentration and age in men (P < 0.001). Daily intake of selenium in men and women was calculated to be 67 microg and 62.1 microg respectively. CONCLUSION: Our results show that the serum concentration of selenium in an Iranian population is similar to other nationalities in the Middle East, particularly Saudi Arabia.

Adolescent↗

PubMed2003

Presentation serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin's lymphoma.

PURPOSE: This study was undertaken to test the hypothesis that serum selenium concentration at presentation correlates with dose delivery, first treatment response, and overall survival in patients with aggressive B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: The patients presented between July 1986 and March 1999 and received anthracycline-based chemotherapy, radiotherapy, or both. The total selenium content was retrospectively analyzed in 100 sera, frozen at presentation, using inductively coupled plasma mass spectrometry. RESULTS: The serum selenium concentration ranged from 0.33 to 1.51 micromol/L (mean, 0.92 micromol/L; United Kingdom adult reference range, 1.07 to 1.88 micromol/L). Serum selenium concentration correlated closely with performance status but with no other clinical variable. Multivariate analysis revealed that increased dose delivery, summarized by an area under the curve, correlated positively with younger age (P <.001), advanced stage (P =.001), and higher serum selenium concentration (P =.032). Selenium level also correlated positively with response (odds ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.90; P =.011) and achievement of long-term remission after first treatment (log-rank test, 4.38; P =.036). On multivariate analysis, selenium concentration was positively predictive of overall survival (hazard ratio [HR], 0.76 for 0.2 micromol/L increase; 95% CI, 0.60 to 0.95; P =.018), whereas age indicated negative borderline significance (HR, 1.09; 95% CI, 0.99 to 1.18; P =.066). CONCLUSION: Serum selenium concentration at presentation is a prognostic factor, predicting positively for dose delivery, treatment response, and long-term survival in aggressive non-Hodgkin's lymphoma. Unlike most existing prognostic factors in aggressive non-Hodgkin's lymphoma, selenium supplementation may offer a novel therapeutic strategy in this frequently curable malignancy.

Adult↗

PubMed2002

Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.

In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.

Adult↗

PubMed1992

Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium.

The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.p.), there was a significant inhibition of the activities of aminopyrine (AM) N-demethylase and ethylmorphine (EM) N-demethylase, and cytochrome P-450 levels but no change in the activities of aniline (AN) hydroxylase, 7-ethoxycoumarin (EC) O-deethylase, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase, and cytochrome b5 content. Chronic administration of selenium in the drinking water (1 or 2 ppm selenium) for 12 weeks, resulted in no alteration in any of the parameters measured. However, significant decreases in activities of AM N-demethylase and AN hydroxylase, and cytochrome P-450 levels were detected in animals given higher doses of selenium (4 or 8 ppm selenium). Following the in vitro additions of selenium to hepatic microsomes obtained from untreated mice, selenium inhibited the AM N-demethylase, AN hydroxylase and 7-EC O-deethylase in a concentration-dependent manner, but no alteration in NADPH-cytochrome c reductase and cytochrome P-450 levels was observed. These results indicate that selenium is a specific from inhibitor of hepatic monooxygenase.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1978

Interaction between selenium and methylmercury.

The available data on the influence of selenium on the toxicity of methylmercury and of methylmercury on selenium as a nutrient and toxic agent are reviewed. Selenium as selenite has a relative protective effect on acute and subacute toxicity of methylmercury in the rat and the quail. The protective mechanism is far from clear. Of special interest is the fact that selenium-treated animals may remain unaffected, even when they have attained tissue mercury levels otherwise associated with toxic effects. Selenite causes some increase of tissue mercury levels in methylmercury-exposed animals. On the other hand, methylmercury induces a remarkable enhancement of organ concentrations of selenium in animals given selenite. The interaction between selenium and methylmercury is in many ways different from that between selenium and inorganic mercury, and also from that between selenium and other metals. Due to the considerable interspecies differences in the toxicity of methylmercury, the available data do not allow conclusions on interactions in man. Practical implications of a possible protective effect of selenium on methylmercury toxicity in humans are discussed.

Animals↗

PubMed2005

Selenium status of idiopathic infertile Nigerian males.

Selenium concentration in the sera and seminal plasma of 60 infertile males (40 oligospermia and 20 azoospermia) and 40 males with proven evidence of fertility (normospermia; control group) were estimated using atomic absorption spectrophotometry. Results were correlated with spermatogram and hormonal levels in order to determine their relationship and significance in male infertility. The mean serum concentrations of selenium was found to be significantly increased in oligospermic compared to azoospermic subjects and controls (p < 0.01), whereas the seminal plasma level was significantly higher in azoospermic compared to oligospermic subjects and controls (p < 0.001). Thus, the ratio of serum selenium to seminal plasma selenium was 1: 1 in controls, 4: 1 in oligospermia, and 1: 2 in azoospermic subject.A significant inverse correlation was observed between serum selenium level and sperm count (p < 0.01). Similarly, seminal plasma selenium correlated with spermatozoa motility, viability, and morphology. Serum selenium level shows positive correlation with the serum testosterone level (p < 0.01). In conclusion, there appears to be a physiological balance in the distribution of selenium in serum and seminal plasma compartment of control males. A disturbance in this balance has a significant influence on spermatogenesis. Selenium appears to have a positive influence on Leydig cells, thus influencing the secretion of testosterone.

Adult↗

PubMed2005

Plasma and erythrocyte selenium and glutathione peroxidase activity in preterm infants at risk for bronchopulmonary dysplasia.

The purpose of this study was to examine the relationships between selenium status, as measured by plasma and erythrocyte selenium and glutathione peroxidase (GPx) activity, and other postnatal factors, including selenium intake, gestational age, and oxygen dependence in preterm infants at risk for bronchopulmonary dysplasia. Eighteen preterm infants of 30 wk gestational age or less were included. At postnatal wk 1 and 4, selenium concentrations and GPx activity were measured and oxygen dependence and daily selenium intakes were determined from the medical chart. Plasma and erythrocyte selenium concentrations decreased from wk 1 to wk 4, whereas erythrocyte GPx activity increased. Increased selenium intakes during wk 1 were associated with increased erythrocyte GPx activity at both time-points, as well as a decreased need for supplemental oxygen on d 28. Preterm infants display increasing erythrocyte GPx activity despite declines in plasma and erythrocyte selenium. GPx activity might be enhanced by very early selenium supplementation.

Bronchopulmonary Dysplasia↗

PubMed2006

Selenium supplementation and blood rheological improvement in Japanese adults.

In order to study the prevention effect of selenium in the development of cardiovascular disease, we investigated the effects of selenium supplementation on the blood rheological properties. Eleven healthy adults were administered with 200 microg of selenium in the form of selenium yeast per day for 1 wk. Before and after the supplementation, serum selenium concentration, glutathione peroxidase (GPx) activity, biochemical indices, and the blood fluidity of the subjects were measured. The blood fluidity was measured using a (microchannel array flow analyzer) by the passage time of 100 microL of heparinized whole blood through the microchannel array. The selenium supplementation significantly (p = 0.001) shortened the mean blood passage time from 44.0 +/- 5.7 to 37.5 +/- 2.8 s. Serum selenium concentration significantly (p = 0.008) increased from 109.8 +/- 10.2 to 124.5 +/- 16.7 microg/L. Meanwhile, the GPx activity did not increased significantly (p = 0.058). The mean GPx activity of the subjects before supplementation was 171.0 +/- 16.1 Deltammol NADPH/min/L and 180.9 +/- 17.8 Deltammol NADPH/min/L after supplementation. Factor analysis of the passage time and biochemical indices of the subjects showed that blood fluidity improvement was related to the metabolic modification of lipoproteins during the selenium supplementation. These results showed that selenium supplementation improved the blood fluidity, without increasing the GPx activity of the subjects.

Adult↗

PubMed2000

Effect of dietary copper on selenium toxicity in Fischer 344 rats.

The purpose of this study was to investigate the ameliorating effects of dietary copper supplementation on selenium toxicity. Nine groups (n = 6) of weanling Fischer 344 female rats were randomly assigned to treatment groups and fed diets containing nontoxic levels of copper as CuCl2 and/or selenium as selenite or selenocystamine. Weight gain, liver and spleen weights, plasma lipid peroxidation, and liver selenium and copper content were analyzed after the 6-wk treatment period. Concentrations of up to 10 times the daily lethal dose of dietary selenium were well tolerated in rats supplemented with dietary copper. As the dietary level of selenium was increased, the ratio of selenium to copper measured in the liver decreased. In the groups of rats in which dietary copper supplementation was absent and dietary selenium was supplemented, copper stores in the liver remained unchanged from control values. Copper's protective effects from dietary selenium toxicity may come from the formation of a copper-selenide complex that renders both selenium and copper metabolically unavailable and nontoxic.

Animals↗

PubMed2002

Selenium status of pregnant women and newborns in the former Soviet Union.

The estimation of the selenium status during pregnancy is of great importance because of the significance of selenium for fetus growth and antioxidant protection of neonates. This problem is especially urgent for Russia and its neighbors because very little data are available and because data on soil selenium predict low intake levels of selenium. A large epidemiological investigation made in various areas of the former USSR allowed us to obtain the first information concerning the subject. Serum samples were obtained during 1990-1998 from 556 female blood donors aged 20-53 yr and 722 pregnant women (18-33 yr) during different times of gestation. The mean serum selenium concentration of nonpregnant women varied from 0.87 micromol/L (Slavutich, Ukraine) to 1.74 micromol/L (Ioshkar-Ola, Mary-El) and that of women at delivery from 0.66 micromol/L (Zaporozie, Ukraine) to 1.34 micromol/L (Sakhalin, Russia). Compilation of literature and present data on serum selenium showed the following relationships: nonpregnant women versus women at delivery, y = x -0.25, r = 0.94; women at delivery versus umbilical serum, log y = log x -0.2, r = 0.97. The two relationships were used to predict serum selenium values for pregnant women taking into account the progressive serum selenium decrease during advancing pregnancy. In almost half of the towns (i.e. 22-50%), pregnant women were considered to have relative selenium deficiency.

Adult↗

PubMed1997

Effects of selenium and iodine deficiency on thyroid hormone concentrations in the central nervous system of the rat.

OBJECTIVE: The effects of single and combined nutritional selenium and iodine deficiency on intracellular thyroid hormone concentrations and type II 5'-iodothyronine deiodinase (5'D-II) activity were examined in different regions of the adult rat brain. DESIGN: Four groups (n = 6) of weanling female Wistar rats proceeding from a breeding line fed a selenium-deficient or a selenium-replete diet for 3 generations, were fed selenium-deficient, iodine-deficient, combined selenium- and iodine-deficient or selenium- and iodine-replete diets for 2 months before they were killed. METHODS: Tissue thyroxine (T4) and tri-iodothyronine (T3) concentrations were determined by highly sensitive RIAs after extraction of the iodothyronines from the tissue samples. The measurement of 5'D-II was based on the release of radioiodide from the 125I-labelled substrate. RESULTS: Selenium deficiency significantly decreased tissue T3 concentrations in the hippocampus, hypothalamus and striatum to 70-80% of controls, whereas no significant changes were found in the cerebellum, cerebral cortex and brain stem. Tissue T4 concentrations were only marginally affected with the exception of a 35% increase in the cerebral cortex. Iodine deficiency dramatically diminished serum T4 levels as well as intracellular T4 concentrations in all regions examined up to 10-30% of control. In spite of a threefold enhancement of 5'D-II, the iodine-deficient animals still had a significant reduction of tissue T3 concentrations (50-65% of controls) in all regions excepting the cerebellum. The combination of selenium and iodine deficiency did not significantly alter this pattern of changes. CONCLUSIONS: These findings suggest that prolonged selenium deficiency as well as iodine deficiency may compromise thyroid hormone homeostasis in the adult brain leading to tissue hypothyroidism and therefore to impaired brain function.

Animals↗