Selenium in total parenteral nutrition

In clinical practice, selenium deficiency may arise under conditions of chronic malnutrition and especially after long-term total parenteral nutrition (TPN). In infants receiving long-term TPN, we observed plasma selenium levels as low as those previously reported in Chinese children with Keshan disease. Low plasma selenium levels were also usually associated with very low activities of glutathione peroxidase. Although clinical symptoms of selenium deficiency did not occur in our patients, several cases have been described in the literature, indicating the need for supplementation in TPN. In order to derive at the appropriate dosage, it is proposed to correlate it with the total protein supply. According to our present knowledge, .5–1.0 μg selenium/g of protein appears to be adequate to keep patients in Se balance. For Se repletion of body stores, this dosage has been increased up to 3 μg of Se/g of protein. Advantages and disadvantages of selenite and of selenomethionine as possible supplemental forms of Se for TPN solutions are discussed.     

Biogeochemical regioning problems and the biogeochemical selenium provinces in the former USSR

Current trends in biogeochemical research in the former USSR are exemplified for the trace element selenium (Se). Vast regions of the former USSR are low in Se, giving rise to selenium deficiency diseases in animals and to Kaschin-Beck disease in humans, whereas isolated high-Se regions are comparatively rare. The Se content of plants depends on geological soil-type and secondary processes such as weathering and leaching. In general, a direct correlation between the Se content of feedstock and of the blood in animals is observed, whereas corresponding data for humans remain to be accumulated.     

Selenium and thyroid function in infants, children and adolescents

Selenium is an integral component of the enzymes glutathione peroxidase (GPx) and iodothyronine deiodinases. Although selenium nutrition could conceivably affect thyroid function in infants, children and adolescents, available data suggest that the effect of selenium deficiency on thyroid function is relatively modest. In patients with isolated selenium deficiency (such as patients with phenylketonuria receiving a low-protein diet), peripheral thyroid hormone metabolism is impaired but there are no changes in thyrotropin (TSH) or clinical signs of hypothyroidism, suggesting that these patients are euthyroid. Selenium supplementation may be advisable to optimize tissue GPx activity and prevent potential oxidative stress damage. In areas where combined selenium and iodine deficiencies are present (such as endemic goiter areas in Central Africa), selenium deficiency may be responsible for the destruction of the thyroid gland in myxoedematous cretins but may also play a protective role by mitigating fetal hypothyroidism. In these areas, selenium supplementation should only be advocated at the same time or after iodine supplementation. In patients with absent or decreased production of thyroid hormones and who rely solely on deiodination of exogenous L-thyroxine for generation of the active triiodothyronine (such as patients with congenital hypothyroidism), selenium supplementation may optimize thyroid hormone feedback at the pituitary level and decrease stimulation of the residual thyroid tissue.     

Etiologic factors and pathologic alterations in selenium-vitamin E deficiency and excess in animals and humans

The etiology of selenium-vitamin E (Se-E) deficiency diseases may be complex. Many of the syndromes involve combined deficiency of selenium and vitamin E. Selenium moves into the animal and human food chain from soil and plants, which may contain inadequate amounts of the nutrient in many areas of the world. Vitamin E may be in low concentration in many animal feeds unless supplements are added. Some syndromes, such as steatitis in cats, result from an increased requirement of vitamin E in diets that contain large amounts of polyunsaturated fatty acids, and these diseases will only respond to vitamin E administration. Deficiency syndromes in animals owing to pure Se deficiency are infrequent and have been produced mainly by laboratory studies utilizing extreme deficiency conditions. Other factors that may affect the occurrence of these deficiency diseases are concurrent dietary deficiency of S-containing amino acids, bioavailability of different forms of dietary Se, intake of compounds that antagonize Se (e.g., silver salts), and exposure to various prooxidant substances (e.g., iron compounds, oxygen, ozone, and various drugs). A wide variety of pathologic alterations occur in animals and humans with Se-E deficiency. Myocardial lesions are seen most frequently in calves, lambs, pigs, turkey poults, and ducklings. In humans, Keshan disease, an endemic cardiomyopathy in China, is attributed to Se deficiency. Necrosis of skeletal muscle is the most frequent lesion observed in animal species. Necrosis of smooth muscle of the gizzard and intestine may be a prominent lesion in turkey poults, ducklings, and quail. Other Se-E deficiency lesions include hepatic necrosis, gastric ulceration, intestinal and uterine lipofuscinosis, pancreatic damage, steatitis, exudative diathesis, encephalomalacia, and testicular necrosis. Selenium toxicosis is well characterized in animals and humans by neurological, hoof, and hair alterations.     

The Effect of Different Levels of Selenium in Mineral Mixtures and Salt Licks on Selenium Status in Sheep

This paper describes 3 experiments comparing the effect of 10, 25 and 40 mg Se/kg, as sodium selenite, in mineral mixtures and salt licks fed to sheep. The supplement was given during the indoor season from October to May to 7 different flocks, each consisting of 50 to 100 sheep, in areas with selenium deficiency problems. The average selenium level in the basic diets did not exceed 0.05 mg/kg. Selenium status was monitored in the blood of ewes and lambs, and in milk. Blood selenium in lambs correlated well with blood selenium in their dams (r = 0.85). Selenium levels in milk on day 1 (colostrum) correlated well with selenium levels in dams (r = 0.92) and in offspring (r = 0.87). Statistically significant differences were found between the different flocks. In areas with extreme selenium deficiency, 10 mg Se/kg in mineral mixtures and salt licks proved insufficient. A content of 25 mg Se/kg, providing a daily intake of about 0.4 mg selenium, resulted in selenium levels in ewes’ blood, ewes’ milk and in the offspring that should prevent selenium deficiency disease without causing any toxic effects.     

Selenium concentration and glutathione peroxidase activity in selenium and magnesium deficient rats

To clarify the effects of selenium (Se) and magnesium (Mg) deficiencies on Se and glutathione peroxidase (GSHPx) status, weanling male Wistar rats weighing 50–60 g were placed on four kinds of diets divided by two levels of Se (0.5 or 0.019 mg/kg) and Mg (500 or 50 mg/kg) for 8 wk. Magnesium deficiency had an influence on distribution of Se, which was increased in muscle and decreased in other tissues. The changes in GSHPx matched those in Se. The levels of Se and GSHPx in most tissues were lower in Se-Mg-deficient rats than in Se-deficient rats. Thus, selenium and Mg deficiencies would make oxidant lesion more serious than Se deficiency.     

微量元素硒在对抗COVID-19中的作用研究进展

自新型冠状病毒肺炎（corona virus disease 2019，COVID-19）疫情爆发以来，严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome-coronavirus 2， SARS-CoV-2）引起的各类临床表现和后续并发症受到了广泛关注。有研究发现，COVID-19死亡率具有地域差异性，中度或重度缺硒地区感染人群常常具有更高的死亡率，因此硒可能在对抗COVID-19中具有一定的作用。总结了硒缺乏COVID-19患者的临床表现、硒对抗COVID-19的临床效应、以及硒对抗COVID-19的作用机制等方面的研究进展。从目前的研究结果来看，硒在应对感染SARS-CoV-2以及避免过激免疫反应导致的细胞因子风暴过程中具有积极作用，但仍然缺乏临床试验研究证据。     

The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma

Patients with systemic inflammatory response syndrome (SIRS) and sepsis exhibit decreased plasma selenium and glutathione peroxidase activity. This has been shown in several clinical studies. Moreover, the degree of selenium deficiency correlates with the severity of the disease and the incidence of mortality. Patients with SIRS and sepsis are exposed to severe oxidative stress. Selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and are involved in the regulation of inflammatory processes. Therefore, selenium substitution in those patients might be effective in the prevention of multiorgan failure. The results of randomised clinical trials investigating selenium substitution in critical ill patients with inflammation are reviewed. In two independently performed randomised, prospective clinical trials, including patients with systemic inflammatory response syndrome or sepsis, the supplementation of selenium revealed a significant reduction in multiorgan failure and, especially, a lower incidence of acute renal failure and respiratory distress syndrome. One of those trials also could demonstrate a significant reduction of mortality in the most severely ill patients. Two other studies, where selenium together with other trace elements or a mixture of antioxidants were used in the treatment of patients with severe burn injuries or trauma showed a significant reduction in the secondary infection rate, including sepsis. Thus, selenium supplementation seems to improve the outcome of patients with SIRS, sepsis and severe injury, however, pivotal prospective clinical trials with sufficient statistical power are now necessary to finally prove the efficacy of a selenium supplementation in these diseases.     

Differential effects of dietary selenium (Se) and folate on methyl metabolism in liver and colon of rats

A previous study compared the effects of folate on methyl metabolism in colon and liver of rats fed a selenium-deficient die (<3 μg Se/kg) to those of rats fed a diet containing supranutritional Se (2 mg selenite/kg). The purpose of this study was to investigate the effects of folate and adequate Se (0.2 mg/kg) on methyl metabolism in colon and liver. Weanling, Fischer-344 rats (n=8/diet) were fed diets containing 0 or 0.2 mg selenium (as selenite)/kg and 0 or 2 mg folic acid/kg in a 2×2 design. After 70 d, plasma homocysteine was increased (p<0.0001) by folate deficiency; this increase was markedly, attenuated (p<0.0001) in rats fed the selenium-deficient diet compared to those fed 0.2 mg Se/kg. The activity of hepatic glycine N-methyltransferase (GNMT), an enzyme involved in the regulation of tissue S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), was increased by folate deficiency (p<0.006) and decreased by selenium deprivation, (p<0.0003). Colon and liver SAH were highest (p<0.006) in rats fed deficient folate and adequate selenium. Although folate deficiency decreased liver SAM (p<0.001), it had no effect on colon SAM. Global DNA methylation was decreased (p<0.04) by selenium deficiency in colon but not liver; folate had no effect. Selenium, deficiency did not affect DNA methyltransferase (Dnmt) activity in liver but tended to decrease (p<0.06) the activity of the enzyme in the colon. Dietary folate did not affect liver or colon Dnmt. These results in rats fed adequate selenium are similar to previous results found in rats fed supranutritional selenium. This suggests that selenium deficiency appears to be a more important modifier of methyl metabolism than either adequate or supplemental selenium. The U.S. Department of Agriculture, Agriculture Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination.     

Selenium deficiency in the Federal Republic of Germany

A mean selenium of 123 mg/kg dry wt was observed in 195 samples of agricultural soils, and a mean of .158mg Se/kg dry wt in 304 samples of grassland soils collected at 354 sites in various regions of the Federal Republic of Germany. For grassland soil, a north/south gradient of Se concentrations was observed. In the industrialized regions of the North, higher Se levels were generally observed, the highest value of .652 mg Se/kg dry wt at a site in Northrhine-Westphalia. The mean selenium content of grass from the respective collection sites was .045 mg/kg dry wt in all regions of the FRG, a level insufficient for the maintenance of health of farm animals. The absence of a correlation between the soil-and grass-Se contents indicates that Se uptake by plants is not solely dependent on the presence of Se. Grass may be deficient in Se even if grown on Se-rich soils. Fixation of Se by acidic soils appears to be a major factor; the high Se levels in the soils of industrialized areas is not bioavailable. Based on these findings, it is concluded that locally produced feedstock must be supplemented with Se to prevent the outbreak of deficiency diseases in farm animals.     

Selenium alters the lipid content and protein profile of rat heart: an FTIR microspectroscopic study

Cardiovascular disease is one of the most important causes of morbidity and mortality in Western countries. In addition, it is well documented that selenium (Se) deficiency has been linked to cardiovascular diseases. This study was undertaken to present the effect of sodium selenite on left and right myocardia, and small veins of normal control rat heart at molecular level by using Fourier transform infrared (FTIR) microspectroscopy. The results mainly reveal that, Se treatment causes an increase in lipid content both in the saturated and unsaturated lipids, and an alteration in protein profile with a decrease in alpha-helix and an increase in beta-sheet structure of the rat heart which might be reflecting a slight subtoxic effect of selenium supplementation on normal rat heart at the dose used in this study.     

Selenium status is decreased in patients with intrinsic asthma

Lowered selenium (Se) status has been observed in asthma patients. An increased production of reactive oxygen species (ROS) owing to inflammatory condition has also been found in these patients and thus antioxidant properties of Se via glutathione peroxidase (GPx) activity are of great importance. Concentrations of Se in plasma and erythrocytes as well as eryth-rocyte GPx activity in 22 intrinsic asthma patients (five patients; all women were aspirin-sensitive) were compared with those of 33 control subjects. Se concentrations in both plasma and erythrocytes and GPx activity were decreased in intrinsic asthma patients. There were no significant differences in investigated parameters of Se status between aspirin-tolerant and aspirin-intolerant patients within intrinsic asthma group. Significantly high positive correlation between plasma and erythrocyte Se concentrations was found when regarding all subjects as a whole. Se supplementation might be beneficial to patients with intrinsic asthma, which may be at risk of Se deficiency.     

Relationship between serum Se concentration in dogs and incidence of some disease conditions

The aim of the study was to determine if there is a relationship between serum selenium concentration in dogs and their health, and to assess the relationship between selenium concentration and morphological parameters of blood. Mean serum selenium concentration in dogs ranged from 0.169 to 0.273 mg/ml. Dogs diagnosed with malignant neoplasm had a significantly lower mean concentration of serum selenium compared to healthy dogs and those from the groups studied. The present study showed no statistically significant differences in Se serum content according to sex, age, and food type. Dogs diagnosed with malignant neoplasm had a significantly lower mean serum selenium concentration compared to healthy dogs and those from the other groups analysed, namely with hip dysplasia, allergy and fractures and with non-malignant tumour. Healthy dogs were characterized by the highest mean serum selenium concentration, significantly higher compared to dogs with non-malignant tumour, malignant neoplasm, allergy and fractures. Low levels of selenium contribute to the incidence of neoplasms and allergies and increase the risk of bone fractures in dogs. Additional laboratory tests should be conducted when certain diseases are diagnosed to determine Se concentration in dogs, thus making it possible to take preventive measures or therapeutic action.     

Relationship between selenium status,selenoproteins and COVID-19 and other inflammatory diseases: A critical review

The antioxidant effects of selenium as a component of selenoproteins has been thought to modulate host immunity and viral pathogenesis. Accordingly, the association of low dietary selenium status with inflammatory and immunodeficiency has been reported in the literature; however, the causal role of selenium deficiency in chronic inflammatory diseases and viral infection is still undefined. The COVID-19, characterized by acute respiratory syndrome and caused by the novel coronavirus 2, SARS-CoV-2, has infected millions of individuals worldwide since late 2019. The severity and mortality from COVID-19 have been associated with several factor, including age, sex and selenium deficiency. However, available data on selenium status and COVID-19 are limited, and a possible causative role for selenium deficiency in COVID-19 severity has yet to be fully addressed. In this context, we review the relationship between selenium, selenoproteins, COVID-19, immune and inflammatory responses, viral infection, and aging. Regardless of the role of selenium in immune and inflammatory responses, we emphasize that selenium supplementation should be indicated after a selenium deficiency be detected, particularly, in view of the critical role played by selenoproteins in human health. In addition, the levels of selenium should be monitored after the start of supplementation and discontinued as soon as normal levels are reached. Periodic assessment of selenium levels after supplementation is a critical issue to avoid over production of toxic metabolites of selenide because under normal conditions, selenoproteins attain saturated expression levels that limits their potential deleterious metabolic effects.     

Selenium Attenuates Adriamycin-Induced Cardiac Dysfunction via Restoring Expression of ATP-Sensitive Potassium Channels in Rats

The possible mechanism of adriamycin (ADR) and/or selenium (Se) deficiency-induced cardiac dysfunction, and cardioprotective effects of Se against ADR-induced cardiac toxicity were investigated in this study. Cardiac function was evaluated by plasma brain natriuretic peptide level and echocardiographic and hemodynamic parameters. Cardiac glutathione peroxidase (GPx) activity was assessed spectrophotometrically. Expression of ATP-sensitive potassium channels (K_ATP) subunits—SUR2A and Kir6.2—were examined by real-time PCR and Western blotting. The results showed that cardiac function and cardiac GPx activity decreased remarkably after administration of ADR or Se deficiency; more dramatic impairment of cardiac function and cardiac GPx activity were observed after co-administration of ADR and Se deficiency. Mechanically, it is novel for us to find down-regulation of K_ATP subunits gene expression in cardiac tissue after administration of ADR or Se deficiency, and more significant inhibition of cardiac K_ATP gene expression was identified after co-administration of ADR and Se deficiency. Furthermore, cardiac toxicity of ADR was found alleviated by Se supplementation, accompanied by restoring of cardiac GPx activity and cardiac K_ATP gene expression. These results indicate that decreased expression of cardiac K_ATP is involved in adriamycin and/or Se deficiency-induced cardiac dysfunction; Se deficiency exacerbates adriamycin-induced cardiac dysfunction by future inhibition of K_ATP expression; Se supplementation seems to protect against adriamycin-induced cardiac dysfunction via restoring K_ATP expression, showing potential clinical application in cancer chemotherapy.     

Food system-based approaches to improving micronutrient nutrition: the case for selenium

Micronutrient deficiencies affect nearly half the world's population, impairing child development, reducing work productivity, and increasing mortality and morbidity rates by affecting both infectious and chronic diseases. To feed a growing world, it will be necessary to consider agriculture in the broad context of a food system as an instrument of public health and, thus, to address nutrient balance while also seeking sustainability. Such efforts would include increasing cropping system diversity, enhancing micronutrient outputs and promoting environmental sustainability. Example of this approach are presented for the essential trace element selenium (Se), which at high intakes can reduce cancer risks but is deficient in many parts of the world. Food systems-based approaches are discussed for preventing Se deficiency by enhancing intakes of any of several biologically available forms of Se, and for reducing cancer risk by enhancing intakes of forms of the element that support anti-tumorigenic Se-metabolites.     

Selenium supplementation of symptomatic human immunodeficiency virus infected patients

The mean whole blood selenium levels in male San Diego, CA patients with acquired immune deficiency syndrome (AiDS) are 0.123 +/- 0.030 micrograms/mL (n = 24), and 0.126 +/- 0.038 micrograms/mL (n = 26) in patients with AIDS-related complex (ARC), compared to 0.195 +/- 0.020 micrograms/mL (n = 28) in San Diego healthy controls (males). To establish whether intestinal absorption of dietary selenium is impaired in AIDS or ARC, a supplementation trial was conducted in which 19 symptomatic HIV-antibody positive male patients with AIDS or ARC were taking 400 micrograms of selenium/d in form of selenium yeast for up to 70 d. The mean whole blood Se levels increased to 0.28 +/- 0.08 micrograms/mL after 70 d of supplementation, the selenium supplements were well tolerated. A rationale for adjuvant selenium supplementation of symptomatic and asymptomatic HIV carriers is proposed.     

Selenium, oxidative stress, and health aspects

Metabolic processes which generate oxidants and antioxidants are governed by genetic disposition as well as environmental factors. Changes in lifestyle, including increased environmental pollution, sun exposure, and dietary habits modify the challenge of the organism by reactive oxygen species. Defense mechanisms are reinforced by increasing dietary intake of antioxidants and micronutrients such as vitamins and selenium (Se). Se deficiency has been recognized to promote some disease states. Epidemiological findings link a lowered Se status to neurodegenerative and cardiovascular diseases as well as to increased cancer risk. While evidence exists to suggest that additional selenocompounds would be beneficial in some health conditions, results from future intervention trials are needed to substantiate the argument for increasing Se intake. Several pieces of the puzzle concerning the molecular mechanisms underlying the reactive oxygen species-triggered disease state and intervention by enzymatic antioxidants have been elucidated. A novel concept of protection of stromal cells against the dominating influence of tumor cells in tumor-stroma interaction by selenocompounds and other antioxidants is presented herein, which may translate into therapeutic strategies in chemoprevention of tumor invasion.     

The chemical form of selenium affects insulinomimetic properties of the trace element: investigations in type II diabetic dbdb mice

The objective of the present study was to investigate the effects of oral selenate application in comparison to selenium deficiency and selenite treatment on the development of the diabetic status (glucose tolerance, insulin resistance and activities of glycolytic and gluconeogenic marker enzymes) in dbdb mice, representing a type II diabetic animal model. Therefore 21 adult male dbdb mice were assigned to 3 experimental groups of 7 animals each and put on a selenium deficient diet (< 0.03 mg/kg diet) based on torula yeast. Group 0Se was kept on selenium deficiency for 10 weeks while the mice of the groups SeIV and SeVI were supplemented daily with 15% of their individual LD(50) of sodium selenite or sodium selenate in addition to the diet. After 10 weeks a distinct melioration of the diabetic status indicated by a corrected glucose tolerance and a lowered insulin resistance was measured in selenate treated mice (group SeVI) in comparison to their selenium deficient and selenite treated companions and to their initial status. Activities of the glycolytic marker enzymes hexokinase, phosphofructokinase and pyruvate kinase were increased 1.7 to 3-fold in liver and/or adipose tissue by selenate treatment as compared to mice on selenium deficiency and mice with selenite administration. In contrast selenate treatment (SeVI) repressed the activity of liver pyruvate carboxylase the first enzyme in gluconeogenesis by about 33% in comparison to the selenium deficient (0Se) and selenite treated mice (SeIV). However the current study revealed an insulinomimetic role for selenate (selenium VI) also in type II diabetic animals due to a melioration of insulin resistance. In contrast selenium deficiency and especially selenite (selenium IV) impaired the diabetic status of dbdb mice, demonstrating the need for investigations on the insulinomimetic action of selenium due to the metabolism of different selenium compounds.     

MiR‐128‐1‐5p regulates tight junction induced by selenium deficiency via targeting cell adhesion molecule 1 in broilers vein endothelial cells

Vein endothelial cells (VECs) constitute an important barrier for macromolecules and circulating cells from the blood to the tissues, stabilizing the colloid osmotic pressure of the blood, regulating the vascular tone, and rapidly changing the intercellular connection, and maintaining normal physiological function. Tight junction has been discovered as an important structural basis of intercellular connection and may play a key role in intercellular connection injuries or vascular diseases and selenium (Se) deficiency symptoms. Hence, we replicated the Se‐deficient broilers model and detected the specific microRNA in response to Se‐deficient vein by using quantitative real time‐PCR (qRT‐PCR) analysis. Also, we selected miR‐128‐1‐5p based on differential expression in vein tissue and confirmed its target gene cell adhesion molecule 1 (CADM1) by the dual luciferase reporter assay and qRT‐PCR in VECs. We made the ectopic miR‐128‐1‐5p expression for the purpose of validating its function on tight junction. The result showed that miR‐128‐1‐5p and CADM1 were involved in the ZO‐1‐mediated tight junction, increased paracellular permeability, and arrested cell cycle. We presumed that miR‐128‐1‐5p and Se deficiency might trigger tight junction. Interestingly, miR‐128‐1‐5p inhibitor and fasudil in part hinder the destruction of the intercellular structure caused by Se deficiency. The miR‐128‐1‐5p/CADM1/tight junction axis provides a new avenue toward understanding the mechanism of Se deficiency, revealing a novel regulation model of tight junction injury in vascular diseases.