**1. Introduction**

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The element selenium was first described by the Swedish chemist Jöns Jacob Berzelius in 1818, who found this element in the mud at the bottom of a sulfuric acid preparation. At that time, it was believed that selenium was toxic [1]. Early research on this element was focused mainly on its toxicity as in the 1930s, it was found that selenium caused the poisoning of livestock (the so-called "alkali disease"), especially in areas with a high amount of selenium in the soil [2]. In agricultural soils, Se exists in two bioavailable inorganic forms as selenate or selenite; plants are able to uptake selenium in these two forms and convert them to organoselenium compounds such as selenocysteine (SeCys) and selenomethionine (SeMet) [3]. Plants are the main source of Se for grazing and forageeating animals such as cattle, horses, sheep, goats, and swine. Forages in which Se levels exceed 5 mg/kg should be considered hazardous for the health of livestock [4]. Some plant species are considered selenium hyperaccumulators (e.g., *Astragalus* spp. and *Senecio* spp.); they tend to easily take up selenium from the soil and accumulate it in high concentrations (1000–15,000 mg Se/kg dry matter) into their tissues [3]. Long-term ingestion of plants or fodder with contents of Se above 1 mg/kg in dry matter (DM) can cause chronic Se toxicity (i.e., selenosis) in livestock [3,5–7]. Young animals tend to be more susceptible to selenium poisoning.

Until the 1950s, selenium was considered to be toxic to humans and animals. However, perceptions of selenium significantly changed in 1957 when Schwarz and Foltz stated that the addition of Se prevented liver necrosis in rats [7]. A few years later, it was found that selenium is incorporated into leucocytes in dogs; this finding indicated the role of

**Citation:** Malyugina, S.; Skalickova, S.; Skladanka, J.; Slama, P.; Horky, P. Biogenic Selenium Nanoparticles in Animal Nutrition: A Review. *Agriculture* **2021**, *11*, 1244. https://doi.org/10.3390/ agriculture11121244

Academic Editors: Lubomira Gresakova and Emilio Sabia

Received: 21 October 2021 Accepted: 5 December 2021 Published: 9 December 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Se in immune function [8]. In 1973, scientists discovered that Se is a component of the enzyme glutathione peroxidase (GPx), which is a selenoprotein that detoxifies harmful organic hydrogen peroxides [9]. In Eukaryotes, over 26 distinct selenoproteins have been identified. However, their functions are not completely understood. All selenoproteins that are known to play a role in oxidoreductase intervening enzymes are implicated in multiple metabolic pathways, e.g., the maintenance of intracellular redox status, free radical scavenging, and repair of oxidized lipids [10]. These discoveries were the beginning of more extensive studies on the role and importance of this element for human and animal health and nutrition. Studies are still ongoing, although selenium is currently recognized as an essential micronutrient that performs multiple functions (e.g., anticancer, joint health, immune resistance, and antioxidant properties) in the growth and functioning of living animal cells and human bodies. As an element of GPx and thioredoxin reductase enzymes, selenium protects the biomolecules against reactive oxygen species (ROS) and free radical damage. Antioxidants can reduce the harmful effects of ROS on animal organisms [11]. The biological activity of Se depends on its chemical form. Selenium compounds commonly exist in four oxidation states in nature: selenate (Se+6), selenite (Se+4), elemental selenium (Se0), and selenide (Se−2). The inorganic forms of Se (i.e., selenates and selenites) are soluble in water and, usually, they present in this form in water, or they can be found in different minerals [12]. They are known to be toxic to biological systems even in low concentrations [13]. In contrast, Se<sup>0</sup> is essentially nontoxic and highly insoluble in water; it rarely occurs in its elemental state. In the form of organic bindings, Se occurs as selenides [12], and these compounds are considered to be the most stable [14].

#### **2. The Importance of Selenium in Animal Nutrition**

Trace elements play an essential role in animal diet. Selenium is one of the critical nutritional factors necessary for the normal functioning of the immune system [15] and maintenance of health, growth, and various biochemical–physiological functions [16]. Numerous scientific investigations have demonstrated that a deficiency in Se could lead to serious disruptions in an animal organism such as liver necrosis, muscular dystrophy, pancreatic fibrosis, mastitis, cystic ovaries, and dysfunction of the thyroid metabolism [17–19]. The symptoms of selenium deficiency have been reported in monogastric animals and ruminants. In young ruminants, such as calves and lambs, Se (and also vitamin E) deficiency often leads to the commonly named "white muscle disease" (WMD) or nutritional muscular dystrophy [20–22]; in older ruminants, a low selenium state is associated with poor reproductive performance, unthriftiness, placental retention, and impaired immunity [18]. In monogastric animals (swine, poultry, and horses), Se deficiency leads to the damage of vital organs, such as the liver, kidney, and pancreas, and to WMD, "Mulberry heart disease" (MHD), lower immune responses, and increased susceptibility to viral infections [18,23]. Selenium deficiency can cause a variety of reproductive disorders in animals (e.g., damage of embryonic development, infertility, retained placenta in dairy cattle, abortions, and a decrease in egg production in laying hens) [24,25]. Selenium deficiency is related to oxidative stress, which refers to the production of a large amount of ROS in the body. ROS can damage cells and tissues and adversely affect organs and their functions. According to the results presented in publications in the field of human medicine, the Czech Republic was ranked among the countries with a low selenium intake, those which had populations that were found to have selenium concentrations below the European average. Thus, sufficient Se supplementation in animals tends to be important not only to maintain the good health and performance of animals themselves but also to increase its supply to the human population through higher selenium content in milk and meat. Selenium plays an important role in maintaining the good health of the mammary gland and, thus, has an impact on milk quality. Selenium deficiency is associated with increased intramammary infections in dairy cattle. When evaluating the occurrence of Se deficiency in cattle by examining the blood of 879 cows in 34 regions in the Czech Republic, selenium deficiency was found on 50% of tested animals and 54% of the farms. Studies from Slovenia and

Ireland have reported similar findings [26,27]. Selenium deficiency is related to various Se concentrations in soils in different regions. Extensive monitoring of Se concentration in soil, plants, animal feed, and blood in 30 farms in different regions in Kosovo showed a low concentration of Se in soil (under 500 μg/kg) and plants (under 50 μg/kg); among all minerals measured in animals blood, the larger deficiency was found for Se [28]. Selenium deficiency in livestock is often related to low Se content in forage and pasture. Compared to the control group, calves supplemented with selenium-fortified hay had higher Se blood concentration and improved body weight and immune response upon vaccination [29]. Nordic countries (e.g., Sweden and Finland) are generally considered to be selenium-poor areas (<0.125 mg/kg) [30–32]. Currently, almost all crop fertilizers in Finland contain Se in the chemical form of sodium selenate (15 mg Se/kg). In areas such as China and North America, where irrigated soils contained excessive Se concentrations (>1 mg/kg), it led to high Se concentrations in surface waters, causing the phenomena of Se pollution, ecological damage, and human diseases [33]. Possible toxic effects for humans and animals as a result of the excessive Se contention in water may be a future challenge. Currently, there is no regulation concerning Se supplementation in animals; however, the National Research Council (NRC) provides guidance. The daily dietary requirements of Se in cattle recommended by NRC are 100 μg/kg of DM for beef cattle and calves, and 300 μg/kg DM per day for dairy cows [34]. Poultry Se requirements range between 150 and 200 μg/kg DM; some diets also include 300 μg/kg DM [35] (Table 1). Current regulations in the US allow up to 300 μg/kg DM of dietary addition of Se in poultry diet, and for the European Union, the total maximal level of dietary Se inclusion is up to 500 μg/kg DM [36]. The dietary Se requirements for swine ranges from 150 μg/kg DM for finishing pigs and sows to 300 μg/kg DM for weaning pigs [37]. Even though selenium is important for many physiological functions in the body, a high dietary level of Se can cause toxicity. Doses of Se which cause acute toxicity in different animal species are represented in Table 2. Signs of acute Se toxicity may vary with the concrete amount of Se consumption or administration, the chemical form of Se, animal age, and species [38], but they usually follow death within 2–5 h after acutely toxic Se consumption or injection of Se [39]. Selenium can be found in all agroecosystems, such as soils, rocks, and water. Acute oral selenium poisoning usually occurs with exposure ranging from 1 to 10 mg/kg bw depending on the species (Table 1), age, and Se chemical form. Young animals are more susceptible to acute Se toxicosis with dosages of 0.2–0.5 mg/kg bw. Parenteral Se products can cause acute toxicity and death at dosages of 1 mg/kg bw [39].

**Table 1.** Selenium daily nutritional requirement (supranutritional) and acute toxic levels in various animal species.





**Table 2.** *Cont.*
