Selenoenzyme activities in selenium- and iodine-deficient sheep

This study was conducted to evaluate the effects of single and combined deficiencies of selenium and iodine on selenoenzyme activities in sheep. Twenty-four male lambs were assigned to one of four semisynthetic diets: combined deficient A (Se⁻I), Se-deficient B (Se⁻I⁺), I-deficient C (Se⁺I⁻), and basal diet D (Se⁺I⁺). Thyroid hormones (T₃, T₄), thyroid stimulating hormone (TSH), and inorganic iodine (PII) were determined in plasma. Selenium and glutathione peroxidase activity (GSH-Px) were determined in erythrocytes, and tissue samples, including the thyroid, liver, kidney, and brain, were taken for selenoenzyme analysis. Plasma T₃, T₄, and TSH concentrations were similar in all groups. Type I deiodinase (ID-I) activity in liver and kidney remained unchanged in Se or I deficiency. In contrast, hepatic ID-I activity was increased by 70% in combined Se-I deficiency. Thyroidal cystolic GSH-Px (c-GSH-Px) and phospholipid GSH-Px (ph-GSH-Px) activities remained constant in both Se-deficient groups, whereas thyroidal c-GSH-Px activity increased (57%) in I deficiency. Type II deiodinase (ID-II) activity was not detectable in the cerebrum and cerebellum, whereas cerebellum Type III deiodinase (ID-III) activity was decreased in I deficiency and combined Se-I deficiencies. The results of the present study support a sensitive interaction between Se and I deficiencies in sheep thyroid and brain. Furthermore, the lack of thyroidal ID-I activity, the presservation of the thyroidal antioxidant enzymes, and the increases in hepatic ID-I indicate that a compensatory mechanism(s) works toward retaining plasma T₃ levels, mostly by de novo synthesis of T₃ and peripheral deiodination of T₄ in Se- and I-deficient sheep.     

Effect of selenium supplementation on thyroid hormone levels and selenoenzyme activities in growing lambs

The aim of the present study was to evaluate the effects of selenium supplementation on thyroid hormone metabolism and selenoenzyme activities in lambs. Twelve 20-d-old male lambs were assigned to one of two diets: A (0.11 ppm Se) and B (supplemented with 0.2 ppm selenium as sodium selenite). Blood samples were collected weekly for the determination of T₃, T₄, and selenium levels. The response to thyrotropin-releasing hormone (TRH) challenge was estimated at the 11th and 20th wk. Animals were slaughtered at wk 20 and tissues were collected for enzyme determination. Plasma selenium concentration was significantly higher in supplemented lambs (p<0.001). Plasma T₃ and T₄ levels remained similar in both groups. Type I deiodinase activity (ID-I) was decreased in the liver (p<0.05) and increased in the pituitary (p<0.01) of supplemented animals. No ID-I activity was detected in the thyroid. Pituitary type II deiodinase activity (ID-II) remained unchanged. The response to TRH challenge did not differ between the two groups for both challenges, but in group B, the second TRH challenge (20th wk) resulted in a significantly higher T₃ response compared to the first one (11th wk) (p<0.05). In conclusion, the lack of effects of Se supplementation on thyroid hormone metabolism demonstrates that enzyme activity is homeostatically controlled and selenium is incorporated in that order to ensure the maintenance of thyroid hormone homeostasis.     

Selenium status indices,laboratory data,and selected biochemical parameters in end-stage renal disease patients

We investigated the relations between selenium status (SeS) parameters, indexes of nutrition, erythropoiesis, and uremic toxemia, serum electrolytes, and other biochemical markers in end-stage renal disease (ESRD) patients, as no multivariate statistical analysis concerning all of these parameters was performed so far. SeS was evaluated by plasma Se concentration (plSe) and glutathione peroxidase (plGSHPx) activity in 69 uremic patients treated with hemodialysis (HD) and 40 healthy controls. The hierarchical multivariate partial least squares model (PLS2) was employed to establish data structure and correlations between parameters investigated. plSe and plGSHPx activity were significantly lower in patients when compared with controls (p=0.000). plSe was positively associated with indexes of erythropoiesis and nutritional status, as well as serum electrolytes and parameters of uremic toxemia. plGSHPx was inversely dependent on the pair of parameters: intact parathyroid hormone (iPTH) and aluminum plasma concentration (Al). We conclude that (1) ESRD strongly decreases selenium status and (2) the PLS2 approach revealed the existence of significant interactions among plSe, plGSHPx, and selected biochemical parameters or groups of such parameters; some of these associations need further studies to be clarified.     

Effect of selenium depletion and supplementation on the kinetics of type 1 5′-iodothyronine deiodinase and T3/T4 in rats

Presently, the effect of selenium (Se) deficiency and excess of Se (1 ppm) on the activity of selenoenzymes type 1 5′-iodothyronine deiodinase (5′-DI), glutathione peroxidase (GSH-Px), and level of thyroid hormones (T₃ and T₄) was studied in rats. Se levels in the serum and liver, T₃ and T₄ in the serum, GSH-Px levels in the liver, and 5′-DI activity in the liver/aorta/thyroid were estimated after 1, 2, and 3 mo of Se-deficient (0.02 ppm), Se-adequate (0.2 ppm), and Se-excess (1 ppm) diet feeding. All of these parameters decreased significantly in the Se-deficient group as compared to the adequate group. Within the deficient group, as the Se deficiency progressed, all of the parameters except 5′-DI decreased after 2 and 3 mo in comparison to 1-mo data. Thyroidal 5′-DI activity in Se deficiency showed the maximum increase. A significant increase was observed in all of the above parameters in the 1 ppm Se-supplemented diet group when compared with the adequate Se group; also, as the Se deposition increased within the Se-excess diet group, a significant increase was observed in all of the above parameters. However, as observed by others, the intake of excess of Se (i.e., 2 ppm in the diet) did not elevate the activities of selenoenzymes and thyroid hormones; rather, it had adverse effects. The present study concludes that Se supplementation at least up to 1 ppm enhances the selenoenzyme activities, and above this level, it may not be considered as an indicator of selenoenzyme activities.     

Content of non-mercury-associated selenium in human tissues

Recent studies have shown that at a higher mercury (Hg) burden, the molar ratio of selenium (Se) and Hg in tissues tends to approximate 1:1 by the formation of biologically largely inert adducts. From the toxicological standpoint, this trapping of free Hg is welcome. However, this binding of Se to Hg reduces the portion of Se in tissues, which is available for the formation of essential selenoenzymes like glutathione peroxidase, type I deiodase, and so forth and could result in a relative deficiency of Se. Therefore, we tried to determine the concentration of non-Hg-associated Se in several human tissues. As there is no proved trace method for the speciation of non-Hg-bound and Hg-bound Se in tissues, the total concentrations of Hg and Se were determined and the portion of non-Hg-associated Se was calculated by the difference of the molar concentrations of Se and Hg. For this investigation, the following tissues were obtained by autopsy from 133 adults: kidney cortex, thyroid gland, liver, spleen, cerebrum cortex, and pituitary gland. In no case was an occupational Hg burden known. The results confirm the assumption of a 1:1 association of Hg and Se in human tissues. The mean concentration of non-Hg-bound Se was calculated to 576 μg/kg in the kidney cortex, 363 μg/kg in the thyroid gland, 308 μg/kg in the liver, 205 μg/kg in the spleen, 111 μg/kg in the cerebrum cortex, and 545 μg/kg in the pituitary gland. In none of the cases under investigation in any tissue was the molar Se/He ratio below 1. This means that a total deficiency of non-Hg-bound Se could not be seen in this normal population, even at a higher Hg burden. Nevertheless, at a suboptimal Se supply like in Germany, any reduction of the part of Se, which is available for the formation of essential seleno-enzymes, should be avoided. Therefore, any additional Hg burden such as from dental amalgam should to be considered critically. The different distribution of Hg and Se in the body confirms that there is a controlled hierarchy in the Se supply of different organs, which tries to prevent a Se deficiency in organs with essential seleno-enzymes like the thyroid gland even under an suboptimal Se supply.     

Abundance and tissue distribution of selenocysteine-containing proteins in the rat

The form and distribution of selenium (Se) in proteins from selected tissues of the rat were studied by measuring 75Se radioactivity in animals provided for 5 months with [75Se]selenite as the main dietary source of Se. Equilibration of the animals to a constant specific activity of 75Se allowed the measurement of 75Se to be used as a specific elemental assay for Se. Skeletal muscle, liver and blood accounted for 73% of the whole-body Se and 95% of the total Se-dependent glutathione peroxidase activity. Over 80% of the whole-body Se was in protein in the form of the selenoamino acid, selenocysteine. All other forms of Se that were measured accounted for less than 3% of the whole-body Se. The Se in protein was distributed in seven subunit sizes and nine chromatographic forms. The Se in glutathione peroxidase accounted for one-third of the whole-body Se. These results show that the main use of dietary Se, as selenite, in rats is for the synthesis of selenocysteine-containing proteins. Furthermore, the presence of two-thirds of the whole-body Se in nonglutathione peroxidase, selenocysteine-containing proteins suggests that there may be other important mammalian selenoenzymes besides glutathione peroxidase.     

The Interaction Between Selenium Status, Sex Hormones, and Thyroid Metabolism in Adolescent Girls in the Luteal Phase of their Menstrual Cycle

The objective of the present work was to study all physiological relationships among selenium status (SeS), sex hormones secretion (SH), and thyroid metabolism (ThM) in healthy adolescent girls, at one time. Forty-four girls aged 13.4–16.6 years (mean age, 14.5 ± 0.5 years) entered the statistical model. Parameters reflecting SeS: plasma selenium concentration (Se) and plasma glutathione peroxidase activity (GPX3); SH: serum estradiol (E₂) and progesterone (P₄); age of menarche (AoM); and ThM: thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), antithyroid peroxidase antibodies (anti-TPO) in serum, and thyroid volume (ThV), were determined, and the interactions between them were evaluated by means of the partial least squares method (PLS). PLS method was, for the first time, successfully applied to the problem of selenium and hormone interactions and revealed that selenium status and female reproductive system are interrelated and affect thyroid physiology in adolescent girls in the luteal phase. The strongest associations were revealed for the pairs of parameters, Se and fT4/fT3, Se and P₄, the modest ones for the pairs, Se and ThV, P₄ and fT4/fT3, Se and AoM, and P₄ and AoM. There was no correlation between E₂, GPX3, and TSH, and any other considered parameter. Se and P₄ had the greatest influence on ThM parameters.     

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.     

The absence of adaptive changes in tissue activities of glutathione-S-transferase, superoxide dismutase and catalase following selenium and vitamin E supplementation in subjects with low selenium status

Three groups of New Zealand women were given daily in a double blind randomised study, 200 micrograms Se as sodium selenite, 170 mg alpha-tocopherol or a placebo for 4 wk. Activities of glutathione-S-transferase, superoxide dismutase and catalase were assayed in erythrocytes, plasma and platelets and in liver and muscle biopsy tissues. No changes in activities of any of these tissue enzymes were observed in any of the three groups. There were also no changes in non-selenium dependent glutathione peroxidase activities in liver or plasma. The lack of changes in any of these enzymes following selenium supplementation suggests that adaptive changes to the low selenium status of these subjects had not occurred through these lipid peroxidation defense mechanisms.     

Selenium status,plasma zinc,copper, and magnesium in vegetarians

Plasma zinc (Zn), copper (Cu), and magnesium (Mg) concentrations, copper/zinc ratio, and selenium (Se) status were studied in 44 vegetarians (22 males and 22 females) and their age- and sex-matched nonvegetarians in the Bratislava region (Slovakia). Vegetarians had statistically significant lower levels of plasma Zn and Cu than nonvegetarians, which may be the result of lower bioavailability of Zn and Cu from this type of diet. No differences in plasma Mg levels were found between vegetarians and nonvegetarians. Se status, as expressed by plasma and erythrocyte concentrations and plasma and erythrocyte glutathione peroxidase activities (GPx), was significantly lower in vegetarians when compared to nonvegetarians. In the series as a whole, there were significantly higher correlations between plasma and erythrocyte Se concentrations and between plasma and erythrocyte GPx activities. Significant positive correlations were also found between plasma Se concentrations and erythrocyte GPx activities, and between erythrocyte Se concentrations and erythrocyte GPx activities. A vegetarian diet does not provide a sufficient supply of essential antioxidant trace elements, like Zn, Cu, and especially Se. Se supplementation should be recommended to this risk group of the population.     

Oxidative DNA base damage, antioxidant enzyme activities and selenium status in highly iodine-deficient goitrous children

The objective of this study was to investigate oxidative DNA damage, and the levels of antioxidant enzymes (AOE) and selenium (Se) in relation to iodine deficiency and/or goiter in children. The study was performed in a group of goitrous high school children (15-18 years of age) ( n =14) with severe or moderate iodine deficiency. Thyroid hormones (TSH, FT 4 , TT 4 , FT 3 , TT 3 ), urinary iodine (UI) and plasma Se levels, and erythrocyte glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were determined and compared with those of a control group consisting of non-goitrous high school children ( n =14) with normal UI levels or mild iodine deficiency. In the goitrous group, concentrations of FT 4 , TT 4 , plasma Se and UI, and activities of GSHPx and SOD were found to be significantly lower. Six typical hydroxyl radical-induced base lesions in genomic DNA of peripheral blood were identified and quantified by gas chromatography/isotope-dilution mass spectrometry (GC/IDMS), and higher levels of DNA base lesions were observed in the goitrous group. The results suggest that highly iodine-deficient goitrous children may be under oxidative stress, which may lead to greater level of oxidative damage to DNA. This study supports the evidence for the reported relationship between iodine deficiency and the increased incidence of thyroid malignancies.     

Acute Phase Response of Selenium Status and Glutathione Peroxidase Activity in Blood Plasma Before and After Total Knee Arthroplasty Surgery

Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p?相似文献   

Selenoenzymes,Laboratory Parameters,and Trace Elements in Different Types of Thyroid Tumor

This study was performed to investigate selenoenzyme activities and trace element concentrations in thyroid tissues, with reference to other parameters routinely used to characterize thyroid function. This was to reveal relevant parameters as possible additional markers of tumor grade, clinical course, and prognosis of thyroid disorders. The tissue samples were obtained during surgical treatment (total or near total thyroidectomy) of 122 patients with different types of thyroid tumor. For most of the investigated parameters in different groups of patients, we did not find statistically significant differences. In the majority of cases, thyroid benign or malignant tumors were not accompanied by significant derangement of the gland selenoenzymes and of either intrathyroidal or plasma concentration of selenium. Nevertheless, types I and II iodothyronine deiodinases were the most promising (among selenoenzymes) targets for diagnoses and possibly therapy of thyroid tumors. Higher activities of both enzymes in cases with Graves’ disease, as compared with other thyroid lesions, suggest their involvement in the pathogenesis of this condition. Patients with struna nodosa had higher levels of thyroid Zn, Cu, and Pb as compared with papillary carcinoma subjects and also a higher level of Cu than follicular carcinoma cases. The above diagnostics may play a similar role to some of the general thyroid function indices, TSH, anti-TG, anti-TPO, and calcitonin, which can partially distinguish between various thyroid tumors. In conclusion, some of selenium status markers, when accompanied with general parameters, and trace elements can serve as factors with pathophysiologic relevance and be helpful in the identification of malignant disease. Multivariate statistical methods should be employed to tackle a broad array of thyroid tumor diagnostic data in a short time. Partial least squares model and other pattern recognition methods seem to be the most appropriate methods for that task. The miniaturization of all the steps of complex analytical procedure should be developed in a way to allow its completion as sensitive, robust, and efficient for use of the small quantity of material provided by fine-needle biopsy.     

The effect of barium selenate injection on selenium concentration and glutathione peroxidase activity in blood of pregnant ewes fed selenium-deficient diet

Selenium (Se) levels in whole blood and plasma, and glutathione peroxidase (GSH-Px) activities in red cells and plasma were measured in ewes fed an Se-deficient diet injected with barium selenate before breeding season. Highly significant increases in Se levels and GSH-Px activities (P<0.001) were observed throughout the gestation period and during lactation. In the control group, Se levels and GSH-Px activities decreased significantly (P<0.001), and were at critically low levels during lambing and lactation periods.     

Role of Glutathione-Dependent Peroxidase in Regulation of Lipoperoxide Utilization in Malignant Tumors

Glutathione content, the activity of glutathione-dependent enzymes (glutathione reductase, glutathione peroxidase, and glutathione S-transferase), and also SOD (superoxide dismutase) and catalase were studied in human malignant tumors (uterus, breast, and ovaries) and normal tissues. Glutathione level and the activity of glutathione-dependent enzymes were 2-3 times higher in the malignant tumors than in normal tissues. A negative correlation between the level of glutathione and glutathione-dependent enzymes (glutathione peroxidase and glutathione S-transferase) in tumors and the efficacy of postoperative chemotherapy may characterize the degree of tumor resistance to chemotherapy and therefore may have prognostic value. Low SOD and catalase activity and high activity of glutathione-dependent enzymes in tumors suggest that glutathione peroxidase and glutathione S-transferase play a major role in peroxide utilization in malignant tumors.     

Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto’s thyroiditis and hypothyroidism

The essential trace element selenium (Se) is required for thyroid hormone synthesis and metabolism. Selenoproteins contain selenocysteine and are responsible for biological functions of selenium. Glutathione peroxidase (GPx) is one of the major selenoproteins which protects the thyroid cells from oxidative damage. Selenoprotein P (SePP) is considered as the plasma selenium transporter to tissues. The aim of this study was to evaluate serum Se and SePP levels, and GPx activity in erythrocytes of children and adolescents with treated Hashimoto’s thyroiditis, hypothyroidism, and normal subjects.Blood samples were collected from 32 patients with Hashimoto’s thyroiditis, 20 with hypothyroidism, and 25 matched normal subjects. All the patients were under treatment with levothyroxine and at the time of analysis all of the thyroid function tests were normal. GPx enzyme activity was measured by spectrophotometry at 340 nm. Serum selenium levels were measured by high-resolution continuum source graphite furnace atomic absorption. SePP, TPOAb (anti-thyroid peroxidase antibody), and TgAb (anti-thyroglobulin antibody) were determined by ELISA kits. T₄, T₃, T₃ uptake and TSH were also measured.Neither GPx activity nor SePP levels were significantly different in patients with Hashimoto’s thyroiditis or hypothyroidism compared to normal subjects. Although GPx and SePP were both lower in patients with hypothyroidism compared to those with Hashimoto’s thyroiditis and normal subjects but the difference was not significant. Serum Se levels also did not differ significantly in patients and normal subjects. We did not find any correlation between GPx or SePP with TPOAb or TgAb but SePP was significantly correlated with Se.Results show that in patients with Hashimoto’s thyroiditis or hypothyroidism who have been under treatment with levothyroxine and have normal thyroid function tests, the GPx, SePP and Se levels are not significantly different.     

New experimental observation on the relationship of selenium and diabetes mellitus

Selenium shows insulin-mimic properties in vitro and in vivo. However, in this study, a high dose of 4 mg/kg/d selenite orally administered to the alloxan-induced diabetic Kun-Ming mice for 4 wk failed to reduce hyperglycemia. Se contents in plasma and tissues such as the liver, kidney, spleen, and brain were determined and the thiobarbituric acid-reactive substances (TBARS) levels were investigated. The results showed that alloxan-induced diabetes did not cause a significant decrease in Se levels in plasma and the above tissues compared to the normal control, but selenite treatment significantly increased Se levels in plasma, liver, and brain of the selenite-treated diabetic mice compared to the nontreated diabetic mice. In addition, selenite treatment for diabetic mice reduced the TBARS levels in red blood cells (RBCs) compared to the normal and improved the glutathione peroxidase (GSH-Px) levels in RBCs significantly compared to the diabetic control. In conclusion, this study demonstrated that although oral administration of a high dose of selenite had no hypoglycemic effect on diabetic mice in 4 wk, selenite treatment still maintained the antioxidant beneficial effect on the diabetic mice. This study shed more light on the relationship between Se and diabetes.     

The mRNA levels of thyrotropin receptor, thyroglobulin and thyroid peroxidase in neoplastic human thyroid tissues

Expression levels of thyrotropin receptor (TSH-R), thyroglobulin (Tg) and thyroid peroxidase (TPO) mRNA in normal and neoplastic human thyroid tissues (6 adenomas and 7 carcinomas) were investigated by Northern-blot and slot-blot analyses. We found that TSH-R mRNA levels were significantly lower in carcinoma tissues than in normal tissues. The levels of Tg mRNA were also significantly lowered in adenoma and carcinoma tissues as compared to normal tissues. In contrast, no significant difference was observed in the expression levels of TPO mRNA between these tissues. Furthermore, TSH-R mRNA levels were well-correlated with Tg mRNA levels in neoplastic tissues. These results suggest that mRNAs of TSH-R and Tg are expressed in relation to their degree of differentiation.     

Biochemical composition of benign thyroid cyst fluid

Although the availability of thyroid cyst fluid is easy by fineneedle aspiration, less is known about the biochemical composition of thyroid cyst fluid. The authors have, therefore, determined the biochemical composition of 18 benign thyroid cyst fluid specimens. They found that the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and the concentrations of total protein, total bilirubin, and uric acid were highly increased in thyroid cyst fluid specimens when compared with normal human serum specimens. The concentrations of glucose, cholesterol, and triglycerides in cyst fluid were within normal serum limits. Selenium (Se) concentrations in most cyst fluids were low. Moreover, there was no correlation between Se and other biochemical parameters. Protein electrophoresis of cyst fluid specimens yielded high concentrations of α₁ and especially α₂ globulin fractions indicating an inflammation. The concentrations or activities of biochemical analytes were not significantly different in pure and mixed cysts. Those parameters were also not significantly different between cyst fluids of different colors. The gross appearance of the fluid and the presence of certain biochemical analytes were consistent with a hemorrhagic origin of most of the cyst fluid specimens. However, some biochemical markers indicate that autolysis or necrosis of thyroid tissue may also contribute the composition of thyroid cyst fluid. The reason for lower Se concentration in the thyroid cyst fluid may be the lower Se concentration in the Turkish population. These results also suggest that the fluid color or nature of cyst, e.g., pure or mixed cyst, is not a main determinant of biochemical composition of benign thyroid cyst fluid.