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УДК : 615.31:546.23-022.513:616.1/.4
Каньовська Л.В., Ляхович О.Д.
Буковинський державний медичний унгверситет DOI: 10.24412/2520-6990-2023-12171-9-12 М1КРОЕЛЕМЕНТ СЕЛЕН ТА МОЖЛИВОСТ1 ЙОГО ЗАСТОСУВАННЯ ПРИ ПАТОЛОГП
ВНУТР1ШН1Х ОРГАН1В
Kaniovska L. V., Liakhovych O.D.
Bukovinian State Medical University
SELENIUM, A TRACE ELEMENT, AND POSSIBILITIES OF ITS APPLICATION IN PATHOLOGY
OF INTERNAL ORGANS
Анотацш.
В останнi роки в медицинi все бгльш уваги придшяють вивченню м1кроелементного статусу ор-гатзму людини i розробц методiв корекцП його порушень при р1зних захворюваннях. Селен - один is бiологiчно важливих мiкроелементiв, який бере участь у багатьох метаболiчних, бюф1зичних та енерге-тичних реакцiях организму, що забезпечують життездаттсть та функци клтин, тканин, оргатв та организму в цтому.
Abstract.
In recent years, in medicine, growing attention has been paid to studying the trace element status of the human body and developing methods for correcting its disorders in various diseases. Selenium is one of the biologically essential trace elements that participates in many metabolic, biophysical and energy reactions of the body, which ensure the viability and functions of cells, tissues, organs and the body as a whole.
Ключовi слова: селен, мтроелементи, iшемiчна хвороба серця, коронавiрус, печтка, гомеостаз.
Key words: selenium, trace elements, coronary heart disease, coronavirus, liver, homeostasis.
Main part. Mineral substances are part of all body cells and tissues, hormones and enzymes. They are necessary for the normal functioning of the cardiovascular, nervous, muscular and other systems, participate in the synthesis of essential compounds, metabolic processes, hematopoiesis, digestion, neutralization of metabolic products harmful to the body, in the construction of body tissues and contribute to the stability of the internal environment. It is recognized that metabolic processes at the cellular and subcellular levels are ensured by the functioning of about 2,000 enzymes, where each catalyzes a corresponding chemical reaction. In turn, the catalytic activity of enzymes is provided by coenzymes of non-protein origin - organic compounds or inorganic elements (metal ions, macro- and microelements)^].
Today, it is well known that violating the metabolic balance of several microelements can contribute to the development and prognosis of many various diseases of internal organs [19]. The role of many trace elements is studied. Among them, a prominent place belongs to selenium, a trace element with significant biological activity and a narrow safety profile, which is vital for human health. Selenium is probably one of the most mysterious and controversial trace elements. After all, for a long time, it was considered exclusively a "poisonous and useless scattered element", as it was described by the discoverer Jens Jacob Berzelius, an outstanding Swedish chemist. In collaboration with Johann Gottlieb Hahn, he was credited with discovering
the trace element in 1817 while studying a red-brown precipitate formed during the production of sulfuric acid from sulfur dioxide. Selenium was named after the goddess of the Moon (translated from Greek - Selene). The essential role of selenium in living organisms was discovered 140 years after its discovery [2].
The biological function of selenium is determined by its position in the periodic table and is closely related to the chemical properties of this element and its compounds [7]. Selenium performs its physiological functions mainly as a component of selenoproteins. Dietary sources of selenium absorption include inorganic forms such as selenate and selenite as well as organic forms such as selenocysteine (Sec) and selenomethionine (SeMet). Each of these forms can be metabolized to selenide, which is an intermediate product in the synthesis of selenocysteine [2].
Selenium is an essential trace element that plays an extremely important role in ensuring the physiological processes of the human body. One of the biologically important trace elements, it is involved in metabolic, biophysical and energy reactions of the body, which ensure the viability and functions of cells, tissues, organs and the body as a whole. It is necessary for the activation of one of the key enzymes of the antiox-idant system - glutathione peroxidase, which prevents the activation of cell membrane lipids peroxidation, the violation of the structural and functional integrity of cell membranes and the reduction of the resistance of cell structures to damaging effects, as well as for the
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synthesis of a number of functional proteins (selenoproteins), due to which realizes antioxidant, anti-inflammatory, antitumor and other properties. A wide range of these selenoproteins are associated with redox signaling, oxidative burst, calcium flux and subsequent effector functions of immune cells, which are grouped into families such as glutathione peroxidases (GPXs), iodothyronine deiodinases (DIOs) and thioredoxin reductases (TrxRs), methionine sulfoxide reductase B1 (MSRB1) and selenophosphate synthetase 2 [2, 11].
Selenium is a trace element that is rarely found in elemental form in nature; instead, organic and inorganic mineral forms of selenium, such as selenide, sel-enate, and selenite, have been found in soil [21]. Previous studies have shown that humans can absorb organic compounds better than inorganic compounds. Selenate is the most abundant inorganic form of selenium in soil; it dissolves in water and reaches rivers and oceans. Organic forms of selenium are found mainly in plant and animal foods, such as selenomethionine and selenocys-teine. Many whole grains, dairy products, meats, and seafood are good sources of selenium, although geographic variations in soil selenium can determine dietary selenium levels. According to the study by Waege-neers et al. (2013), in the diet, the main sources of selenium are meat products and fish.
According to the World Health Organization (WHO) standards, the recommended daily intake of selenium for adults is 55 ^g/day. It is believed that the optimal concentration of selenium in plasma is 90-120 g/l, which is enough to saturate the blood with selenoproteins. People living in regions with low levels of selenium and those with impaired intestinal absorption and chronic hemodialysis are at high risk of developing selenium deficiency [10].
About 15% of the world's population is believed to suffer from selenium deficiency, while its consumption in different countries varies quite a lot. Experimental studies and clinical observations have shown that selenium compounds, in particular, in the form of selenites, have a beneficial effect on the antioxidant status of the body, have cardioprotective, hepatoprotec-tive, radioprotective activity, prevent or inhibit the development of tumor processes, as well as a number of diseases associated with this deficiency trace element. It has been established that sodium selenite, mainly its combination with tocopherol acetate, has a pronounced neuroprotective effect in conditions of total brain ischemia, increasing motor and orientation-research activity [7, 8].
The coronavirus pandemic (COVID-19) has forced scientists to investigate a variety of drugs, including micronutrients, whose administration could contribute to a milder course of the disease. In this context, trace elements such as vitamin C, D, zinc and selenium were studied, which play a role in the body's an-tioxidant, anti-inflammatory, antithrombotic, antiviral and immunomodulating functions [1, 13].
These data suggest that the optimal status of essential nutrients is critical to support both the early vi-remic and later hyperinflammatory phases of COVID-19. Studies have already found a link between selenium deficiency and increased morbidity and mortality from
viral infections, cardiovascular and thyroid diseases, as well as prostate, gastrointestinal and breast cancer. The mechanism of action of selenium as an antiviral agent is that it inhibits the protein disulfide isomerase enzyme, which is responsible for the attachment of viral glycoprotein, and this prevents the virus from entering the host cell. Selenium also reduces the level of IL ip and IL 6, which are pro-inflammatory cytokines. Also it reduces the formation of platelets and the potential formation of blood clots by reducing the level of thromboxane A2 and inhibiting vasoconstriction [3, 17].
In connection with the specifics of the mechanism of action of selenium, some authors have come to a conclusion about its potential benefit in patients with COVID-19, who have an increased risk of developing venous thromboembolism. Summarizing the impact of selenium on COVID-19, Zhang et al. (2020), in an extensive review article, highlighted that selenium involvement through selenoprotein functions and selenium species can counteract SARS-CoV-2 infection. A. Moghaddam et al. (2020) established the need to consider selenium levels in patients with COVID-19. The results of the study confirm the notion of the important role of selenium in the convalescence period of such patients and the feasibility of additional selenium intake [4, 13].
In the human body, as well as in experiments on animals, a spontaneous or experimental decrease in the intake of selenium can lead to an increased risk of developing various pathologies, including cardiovascular diseases (CVD). Selenium deficiency, which is usually the result of nutritional deficiency, has a particularly negative impact in geochemical areas with low selenium content in soil and rocks [14].
Selenium is an essential mineral with antioxidant and immune properties, and selenium deficiency may increase the risk of ischemic heart disease (IHD). However, the effect of selenium supplementation on IHD remains controversial. A meta-analytic study including 16 relevant randomized controlled trials with 43,998 participants showed that selenium supplementation reduced serum C-reactive protein and increased glutathi-one peroxidase, which positively reduced oxidative stress and inflammation in IHD [15].
Selenium-associated cardiomyopathy is a rare but potentially fatal disease. With timely diagnosis, treatment with selenium preparations is effective. Se is an important factor in the biological protection of vascular endothelium, DNA, and chromosomes, an extremely important nutritional agent for preventing ischemic heart disease and inhibiting the development of atherosclerosis (AS), the formation of malignant tumors. The antioxidant activity of Se is the basis of its hepato- and cardioprotective action, which is also carried out with the participation of glutathione. It should be especially noted that Se, like zinc and unlike other metals with variable valence, behaves only as an antioxidant and rarely as a pro-oxidant. Selenium deficiency activates free radicals and develops dystrophic processes, which leads to the development of myocardial dystrophy, atherosclerosis, ischemic heart disease, myocardial infarction, etc. Selenium is an antioxidant that works together with vitamin E [16].
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Selenoprotein P performs the function of selenium transport in various tissues, mainly the brain. It was shown that introducing sodium selenite significantly increases the content of selenoproteins P in the brain compared to other tissues. In contrast, in conditions of selenium deficiency, the capture of selenoproteins P by the brain increases 5 times, while the brain does not utilize low molecular weight selenium compounds. A decrease in the activity of Se-BP1 (selenium-binding protein 1) is pathognomonic for schizophrenia; during its exacerbation, the activity significantly decreases to a critical level, and when it normalizes, there is a significant improvement in the condition of patients. Seleno-protein P also performs antioxidant functions [18].
The use of selenium in patients with cerebrovascular pathology is reasonable and safe. The most effective in terms of preventing arterial hypertension and stroke development is the use of selenium to maintain its concentration in the blood serum in the range from 110 to 115 ^g/l, while it is very important to maintain the level of selenoproteins P in the blood serum of about 63.0 ^g/ l [6, 23].
The data of numerous studies in biochemistry, molecular pharmacology and clinical medicine have confirmed that in the prevention and therapy of iodine deficiency states, the inextricable connection between the metabolism of iodine and the metabolism of other trace elements should be taken into account, primarily selenium as the main molecular synergist [22].
It has been established that selenium deficiency is one of the factors in the development of thyropathies. A decrease in the level of selenium in the blood serum is associated with such pathological changes in the thyroid gland as an increase in volume, a change in echogenicity, the presence of nodular or colloid formations, and lymphoid infiltration. In addition, selenium participates in the antioxidant protection of thyrocytes and activation of thyroid hormones and regulates apoptosis processes. Experimental studies have proven that even under conditions of sufficient iodine intake, a long-term selenium deficiency leads to necrosis and fibrosis of the thyroid gland [3].
Most experts consider selenium to be an insufficient element for the successful treatment and prevention of thyroid diseases associated with iodine deficiency. Additional selenium intake in physiological doses up to 75 ^g/day for 6-12 months is associated with a significant decrease in the titer of antithyroid antibodies, which helps suppress the autoimmune process and improve the echogenic structure according to ultrasound. The combined intake of iodine and selenium allows us to protect the patient from the risk of developing autoimmune thyroiditis. The European Thyroid Association recommends it for iodine prophylaxis in conditions of natural iodine deficiency. As one of the most critical factors in developing and progressing thyroid diseases, Selenium deficiency necessitates introducing effective selenium prevention measures in regions with insufficient consumption of this trace element [3, 7].
Diseases of the gastrointestinal tract are considered polyetiological. Despite the established importance of infectious (bacterial, viral), autoimmune,
alimentary, and other physical, chemical, and biological agents, more and more attention has recently been paid to the role of other components of the relationship between macroorganism and the external environment [9, 22].
Analysis of selenium status and the influence of selenium status during chronic hepatitis, including viral hepatitis, shows a decrease in the content of selenium in the blood serum of patients. A group of scientists studied the relationship between the range of selenium in the blood serum of patients with the persistence of the hepatitis C virus and the level of insulin resistance in these patients. Patients with viral hepatitis C and liver cirrhosis were included in the study. Serum selenium was significantly reduced in proportion to the degree of liver fibrosis. Selenium content was also correlated with serum albumin, zinc, and glutathione perox-idase levels. At the same time, the serum content of selenium was inversely correlated with the level of insulin resistance. Serum selenium levels were independent of the C virus genotype. It was concluded that selenium deficiency is one of the factors contributing to insulin resistance in patients with hepatitis C [12, 20].
Thus, research results indicate that the trace element selenium is one of the basic trace elements, which has anti-inflammatory, antiviral, antioxidant and im-munomodulatory properties.
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