TWO CENTURIES AFTER DISCOVERY OF SELENIUM, STILL BETWEEN MEDICAL USE AND MISUSE IN CLINICAL PRACTICE

Abstract

Selenium (Se), atomic number 34, was discovered as a by-product of sulfuric acid in 1817 by the Swedish chemist and physician J.J. Berzelius. Its name is derived from the Greek: selene (Σελήνη), meaning Moon [1]. In Greek mythology, Selene is the goddess of the Moon. Namely when Se cools rapidly on being melted, it produces sheen similar to that of the Moon [2]. Appropriately, Se was detected in the Moon dust brought by the 1969 Apollo mission [3]. Although discovered before more than two centuries, Se and its role in health and disease remained underestimated and not fully elucidated. Endemic deficiency in large areas of central Asia clearly demonstrated its critical importance for human health and survival. There are two well-established entities of selenopenia: Kashin-Beck osteochondropathy and Keshan disease, severe cardiomyopathy characterized by fulminant heart failure [4, 5]. Concomitant with severe iodine deficiency, selenopenia leads to myxedematous endemic cretinism [6]. Se is present in food in organic form (selenocysteine and selenomethionine) and inorganic form (selenite or selenate). Recommended daily Se intake is 40-70 μg. Plasma Se levels should be kept between 60 and 120 μg/l [7]. It is an active component of selenoproteome, consisted of about 26 selenoproteins, mainly enzymes. The most important are glutathione peroxidases (GPxs; encoded by seven genes), iodothyronine deiodinases (DIs; encoded by three genes,) and three isoforms of thioredoxin reductases (TRx). GPxs protect cells from oxidative stress, the TRx system is involved in development and proliferation. Deiodinase system is essential for T4 to T3 conversion and preservation of iodine from uncontrollable wasting [2, 7]. Underactivity of selenoproteins (especially GPxs) caused by Se deficiency increases the risk for the impaired outcome of pregnancy, exaggerated inflammation, autoimmunity, infertility, cancer, and osteochondropathy [1, 2, 4, 8]. On the other hand, higher concentrations could potentiate the risk of hyperglycemia, insulin resistance, T2DM (Type 2 diabetes mellitus), glaucoma, cancer, hyperlipidemia, atherosclerosis, and increased cardiovascular mortality [2, 9]. Se antiviral effects are nowadays of special interest, as well as its immunomodulatory properties. Namely, Se’s ability to improve the activity of T cells and the cytotoxicity of natural killer cells could render it effective in viral diseases [2]. Se deficiency as an environmental factor increases T-cell activation and shifts Th1/Th2 ratio to a Th1-type response, increasing typical Th1 cytokines as IL-2, TNF-α, IFN-γ, thereby reducing CD25+T regulatory cells (TREG) [1, 2, 4, 9]. It is an immune response typical for autoimmune diseases. However, a recent meta-analysis did not present sufficient data on the clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis (CAT) even in adults, and the authors conclud-