Selenium: An Element of Life Essential for Thyroid Function

Selenium (Se), a microelement essential for life, is critical for homeostasis of several critical functions, such as those related to immune–endocrine function and signaling transduction pathways. In particular, Se is critical for the function of the thyroid, and it is particularly abundant in this gland. Unfortunately, Se deficiency is a very common condition worldwide. Supplementation is possible, but as Se has a narrow safety level, toxic levels are close to those normally required for a correct need. Thus, whether the obtaining of optimal selenium concentration is desirable, the risk of dangerous concentrations must be equally excluded. This review addressed the contribution by environment and food intake on Se circulating levels (e.g., geographical factors, such as soil concentration and climate, and different quantities in food, such as nuts, cereals, eggs, meat and fish) and effects related to its deficiency or excess, together with the role of selenium and selenoproteins in the thyroid pathophysiology (e.g., Hashimoto’s thyroiditis and Graves’ disease).

The Impact of Selenium Deficiency on Cardiovascular Function

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan’s Disease, an endemic disease characterized by cardiomyopathy and heart failure. Since then, Se deficiency has been associated with multiple cardiovascular diseases, including myocardial infarction, heart failure, coronary heart disease, and atherosclerosis. Se, through its incorporation into selenoproteins, is vital to maintain optimal cardiovascular health, as selenoproteins are involved in numerous crucial processes, including oxidative stress, redox regulation, thyroid hormone metabolism, and calcium flux, and inadequate Se may disrupt these processes. The present review aims to highlight the importance of Se in cardiovascular health, provide updated information on specific selenoproteins that are prominent for proper cardiovascular function, including how these proteins interact with microRNAs, and discuss the possibility of Se as a potential complemental therapy for prevention or treatment of cardiovascular disease.

Selenoproteins Protect Against Avian Liver Necrosis by Metabolizing Peroxides and Regulating Receptor Interacting Serine Threonine Kinase 1/Receptor Interacting Serine Threonine Kinase 3/Mixed Lineage Kinase Domain-Like and Mitogen-Activated Protein Kinase Signaling

Liver necroptosis of chicks is induced by selenium (Se)/vitamin E (VE) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms of liver necrosis, a pool of the corn–soy basal diet (10 μg Se/kg; no VE added), a basal diet plus all-rac-α-tocopheryl acetate (50 mg/kg), Se (sodium selenite at 0.3 mg/kg), or both of these nutrients were provided to day-old broiler chicks (n = 40/group) for 6 weeks. High incidences of liver necrosis (30%) of chicks were induced by –SE–VE, starting at day 16. The Se concentration in liver and glutathione peroxidase (GPX) activity were decreased (P < 0.05) by dietary Se deficiency. Meanwhile, Se deficiency elevated malondialdehyde content and decreased superoxide dismutase (SOD) activity in the liver at weeks 2 and 4. Chicks fed with the two Se-deficient diets showed lower (P < 0.05) hepatic mRNA expression of Gpx1, Gpx3, Gpx4, Selenof, Selenoh, Selenok, Selenom, Selenon, Selenoo, Selenop, Selenot, Selenou, Selenow, and Dio1 than those fed with the two Se-supplemented diets. Dietary Se deficiency had elevated (P < 0.05) the expression of SELENOP, but decreased the downregulation (P < 0.05) of GPX1, GPX4, SELENON, and SELENOW in the liver of chicks at two time points. Meanwhile, dietary Se deficiency upregulated (P < 0.05) the abundance of hepatic proteins of p38 mitogen-activated protein kinase, phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, phospho-c-Jun N-terminal kinase, extracellular signal-regulated kinase, phospho-mitogen-activated protein kinase, receptor-interacting serine-threonine kinase 1 (RIPK1), receptor-interacting serine-threonine kinase 3 (RIPK3), and mixed lineage kinase domain-like (MLKL) at two time points. In conclusion, our data confirmed the differential regulation of dietary Se deficiency on several key selenoproteins, the RIPK1/RIPK3/MLKL, and mitogen-activated protein kinase signaling pathway in chicks and identified new molecular clues for understanding the etiology of nutritional liver necrosis.

Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease

The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years—a wise and commendable decision, according to today’s knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.

A Case of Concurrent Molybdenosis, Secondary Copper, Cobalt and Selenium Deficiency in a Small Sheep Herd in Northern Germany

To the author’s knowledge this paper describes the first proven report of a combined primary molybdenosis, secondary copper (Cu) deficiency, Ovine White Liver Disease—Cobalt (Co) deficiency, and selenium (Se) deficiency in a small pedigree herd of White Horned Heath sheep in Germany (8 ewes, 2 rams, 3 yearling ewes, 17 lambs) for decades. Clinical signs associated with these mineral deficiencies in a group of pastured ram lambs included emaciation, conjunctivitis, anaemia, growth retardation, discolouration of the wool and photodermatitis. Morbidities and mortalities arose in 4–6-month-old lambs despite intensive veterinary treatment in the summer of 2014 and 2015 (n = 13, 23% died). Se (3/5), Cu (4/7), and Co (3/3) deficiencies in combination with elevated values for Molybdenum (Mo, 2/2) were found. Hamburg is a large industrial city and an input of heavy metals from surrounding industries and coal-fired power stations in combination with a sandy, non-fertilised soil and monoculture grass species might offer a potential explanation for the severity of mineral deficiencies observed in this herd.

Antenatal Selenium Deficiency Decreases Neonatal Pulmonary Selenium-Containing Antioxidant Enzymes

Objectives Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity. Selenium (Se) deficiency increases the risk for oxygen requirement at 28 days and BPD and thus may be a modifiable nutritional intervention. Se is an essential trace mineral that is incorporated into Se-containing antioxidant enzymes (AOE). An infant's Se status at birth is regulated by the mother's Se supply during pregnancy, however, it is unknown if any neonatal Se-containing AOE in the lung are decreased by antenatal Se deficiency. We hypothesize that antenatal Se deficiency will decrease neonatal pulmonary expression of Se-containing AOE. Methods C57Bl/6 mice were allocated to sufficient (SeS, 0.4 ppm Se) or deficient (SeD, < 0.01 ppm Se) diets before breeding. Breeding pairs were allowed to serially breed, and pups from the 1st-4th pregnancies were evaluated. Pups were sacrificed at PN0. Glutathione peroxidase (GPx) activity was measured in the lung by enzyme activity assay. Pulmonary GPx1, GPx3, thioredoxin reductase 1 (Trxrd1) and selenoprotein N (SelenoN) protein content were measured by Western blot. F and M pups were analyzed as separate groups. Results Weights were similar at postnatal day 0 (PN0) and PN4 for SeS and SeD pups, but by PN7 through adulthood, both male and female SeD mice weighed less then SeS mice. At PN0, pulmonary GPx activity was decreased in all SeD pups, with similar decreases in the protein content of both GPx1 and GPx3 (n = 6–10). We observed a progressive impact of SeD on the pups based on the dam's pregnancy. GPx activity and protein contents were more significantly decreased in pups born after a dam's 3rd or 4th pregnancy than the 1st or 2nd (n = 4–6). Trxrd1 and SelenoN protein content were not decreased in pups born after a dam's 1st or 2nd pregnancy (n = 4–6). However, both were decreased in the lungs of pups born to a dam's 3rd or 4th gestation (n = 6). Conclusions Neonatal pups exposed to antenatal SeD demonstrate decreased pulmonary GPx protein content and activity level without sex differences. Pups born to a SeD dam's third or fourth gestation exhibited a further decline in pulmonary Trxrd1 and SelenoN content. We speculate that SeD neonates may be vulnerable to pulmonary oxidative stresses secondary to low antioxidant enzymatic defense. Impaired ability to respond to oxidative challenge in the lung may predispose SeD infants to BPD. Funding Sources NIH/NHLBI.

Selenium Transport Mechanism via Selenoprotein P—Its Physiological Role and Related Diseases

Selenoprotein P (SELENOP) is selenium (Se)-containing protein in plasma, which is primarily produced in the liver. The “P” in SELENOP originated from the presence in plasma. SELENOP contains selenocysteine, a cysteine analog containing Se instead of sulfur. SELENOP is a multi-functional protein to reduce phospholipid hydroperoxides and to deliver Se from the liver to other tissues, such as those of the brain and testis, playing a pivotal role in Se metabolism and antioxidative defense. Decrease in SELENOP causes various dysfunctions related to Se deficiency and oxidative stress, while excessive SELENOP causes insulin resistance. This review focuses on the Se transport system of SELENOP, particularly its molecular mechanism and physiological role in Se metabolism. Furthermore, the chemical form of Se and its biological meaning is discussed.