The Effects of Selenium Nanoparticles (SeNPs) on Ruminant

This study examines the role of selenium and the effects of selenium nanoparticle-enriched food supplementation especially in ruminant animals. Selenium is an essential element that has multiple biological activities. Particularly it is important for many physiological processes, especially for the functions of reproductive and immune systems, metabolism of thyroid hormones, as well as antioxidant defense. Also, the presence of selenium nanoparticles in the diet provide a high content of selenium in milk and meat due to its high bioavailability and low toxicity, which is essential for humans.


INTRODUCTION
Selenium was discovered in 1817 by the Swedish chemist Jöns Jacob Berzelius. In the beginning, the scientific community thought that selenium was toxic, but in the 1950s it was found that is a biologically essential element lends much support to health maintenance and disease prevention of humans and other all living organisms that is a major structural component of some enzymes and hormones. Actually, its nutritional value depends mainly on the dose and type of selenium species present in the source, such as plant, soil, food, and food supplements. The common dietary supplements of selenium are inorganic selenium (selenate, selenite, selenide, elemental selenium), organic selenium (selenocystine, Semethylselenocysteine), and elemental selenium. A type of nanoparticle (SeNPs) has higher bioavailability [1-3], much lower toxicity [2], and a stronger absorption ability [4] than other general forms, and its applicability is dominated by several significant characteristics such as size, shape, atomic arrangement, structure, and surface charge. On the other hands, its biological properties and application depend on the ability to synthesize particles with different shape, monodispersity, chemical composition, and size.  and intoxication process [25]. The biomedical applications and food supplements of selenium nanoparticles have been increasing based on their properties of non-toxic, high positive effects for prevention and treatment. In this review, we aimed to integrate the functional properties of nano-size selenium and applications of its food supplement for ruminant animals.

THE EFFECT OF SELENIUM NANOPARTICLES ON RUMEN FERMENTATION AND DIGESTION
Rumen fermentation is a fundamental and special process of the ruminant metabolism and it determines the assimilation and intake of nutrients from ingested food. Some studies reported the effect of selenium nanoparticles on rumen microbial fermentation. Wenjuan Xun et al., reported that rumen fermentation and feed utilization improved by nano-size selenium supplementation in the basal diet. Selenium nanoparticles could also stimulate rumen microbial activity, digestive microorganisms, or enzyme activity [5]. These authors studied the effect of nano-size selenium and selenium yeast supplements on food digestibility, rumen fermentation, and found that urine purine derivatives in male sheep demonstrated a decrease in rumen pH, concentration of ammonia nitrogen, level of propionate, and acetate: propionate ratio. The results showed that ruminal fermentation and feed conversion efficiency improved in the nano-size selenium group, and total volatile fatty acid (VFAs) of rumen increased in the supplemented groups like nano-size selenium and yeast-selenium [26].
In another study, selenium supplement improved microbial activity, contributed to higher bioavailability, catalytic efficiency, and strong adsorbing ability. Selenium in ruminant diets is not solely for the animal per selenium but also for rumen bacteria capable of metabolizing part of it [27,28]. Most of the selenium in the rumen fluids of sheep under supplementation is insoluble, indicating the influence of the rumen environment on selenium bioavailability [27,29].
Also, ruminal microorganisms, such as Lactic acid bacteria, Bifidobacteria, and Protozoa (ciliates) alter the bioavailability of received selenium [7]. For example; the study of sheep experiment showed the opposite effect, with higher acetic and isovaleric acids [30] and the total concentration of VFAs, and increased protozoa population, with a greater proportion of Diplodinium [31]. Kheradmand et al. investigated the effect of nano-size selenium on the antifungal activity of probiotic bacteria. After exposure to nano-size selenium-enriched Lactobacillus Plantarum and Lactobacillus Johnsonii, a greater decline in the viability of Candida albicans than after its exposure to non-Se-enriched Lactic acid bacteria was observed. The antifungal activity of both bacterial strains increased through selenium [32].
Faixová Z. et al., reported that selenium affects the activities of Gamma-glutamyl transferase (GGT) and glutamine dehydrogenase (GDH) in the rumen fluid of the sheep. These enzymes were significantly higher after oral administration of selenized yeast, alkaline phosphatase, and aspartate aminotransferase than when sodium selenite (Na2SeO3) was used [33].
The absorption of selenium in the gastrointestinal tract is significantly different between ruminants and non-ruminants. This process is much lower in ruminants than in nonruminants. For example, orally administered selenium was only 34 percent in sheep compared with 85 percent in swine [34]. Low absorption of ruminants is believed to be the result of reduction of dietary selenium to insoluble forms, such as elemental selenium or Proceedings of the Mongolian Academy of Sciences PMAS selenides in the rumen environment [35]. The microbial digestion in the rumen and reticulum precedes digestion in the abomasum and small intestine [36].

THE EFFECT OF NANO-SIZED ELEMENTAL SELENIUM ON REPRODUCTION AND REPRODUCTIVITY
Selenium plays an important role in the synthesis of testosterone and sperm, and sperm motility and its deficiency affects reproductive parameters, such as abnormal mitochondria in spermatozoa and growth performance in male animals. Further oxidative stress affects the fertility potential of spermatozoa by lipid peroxidation, which can lead to sperm dysfunction [11]. Selenium nanoparticle supplementation increases selenium concentration in testes, and testicular and glutathione peroxidase (GPx) activity, which has a protective effect on membrane integrity of the mitochondria. Shi L. et al. reported the effects of nano-size selenium in the diet (0.3 mg/kg body weight for 12 weeks) on the testes ultrastructure, ejaculate quality, and glutathione peroxidase activity in goat. The results of this study showed that the level of selenium in testes and the activity of GPx and ATPase in the ejaculate significantly increased in the nanosize selenium supplemented compared to the unsupplemented group. And the quality of ejaculates, such as volume, density, motility, and pH was not affected, but the percentage of abnormal spermatozoa and damage of spermatozoon membrane was significantly higher in the control group [10].
For female animals, selenium affects pregnancy rates, fertility, embryonic implantation, placenta retention, ovarian cysts, the incidence of metritis, and abortions and stillborn.
The increase of selenium concentration prepartum in blood correlates with anoestrus/silent oestrus decreasing postpartum [12].
The selenium deficiency in grazing beef cattle was the sole cause of abortion in cows [37]. Selenium and vitamin E administration reduces the incidence of retained placenta [9] and it can decrease incidence of metritis and ovarian cysts [10].
In addition, selenium nanoparticle contributes to increasing hair follicle development (wool production) and fetal growth. Generally, selenium intake stimulates the proliferation, migration, and morphogenesis of hair follicle cells through insulin-like growth factor receptor (IGF-1R) during ontogenetic development [38]. Insulin-like growth factor (IGF-1) represents peptide hormone produced in the liver, which is formed as a consequence of growth hormone (GH) released from the pituitary gland, which subsequently stimulates IGF-1 production in liver. IGF-1 is, therefore, a mediator for some of the GH functions, and is thus involved in growth and anabolism. IGF-1 mediates its effects by binding at the specific receptor [39]. The study of Xiaoying Wu et al. found that nano-size selenium supplemented cashmere goats (basal diet with 0.5mg/kg) improved the development of secondary follicles and promoted the growth of the fetus. In the nano-size selenium supplemented group, GSH-Px, IGF-1, and IGF-1R, as well as the activities of GSH-Px and SOD, were significantly higher, but the MDA level was significantly lower. This was attributed to the influencing antioxidant status (T-AOC) in the fetal skin. The weights of fetal liver, kidney tissues, fetus, and placenta were thus significantly higher in nano-size selenium supplemented groups than in the control group [40].

THE EFFECT OF NANO-SIZED ELEMENTAL SELENIUM ON RUMINANT HEALTH
Selenium plays in many physiological functions, which include its ability to protect against certain heart diseases, muscle functioning and development, boost the strength of the immune system (GPx1, TR1), antioxidant activity (GPx), antimicrobial activity, anti-carcinogenic effect, maximize thyroid function (DIO1, DIO2, and DIO3), and Proceedings of the Mongolian Academy of Sciences PMAS intoxication process. Selenium is generally accumulated in immune response organs, such as the spleen, liver, and lymph nodes, which has shown to stimulate the formation of antibodies and the activity of the T helper cells along with cytotoxic T and Natural Killer cells [41]. Selenium supplementation in diet can improve the expression of various humoral and cellular immune responses [42]. The colostrum plays a fundamental role in the passive transfer of immunity from the colostrum to the newborns.
Rasool Kachuee et al. published findings of the effect of organic, inorganic, and nanosize selenium supplements at the final stage of pregnancy on selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) concentrations of Khalkhali goats and placental, colostrum, and milk transfer of these trace minerals from goats to their kids. They used forty pregnant goats, which weree divided into an unsupplemented group, selenomethionine, nano-size selenium, and sodium selenite supplemented groups. The results showed that the whole blood and serum total selenium concentration was higher in the nano-size selenium supplemented group than other groups, which but decreased in their kids. Also copper concentration was greater, zink concentration was totally vice versa in the whole blood, serum, and colostrum, and iron concentration increased at birth and the first week of kids of selenium supplemented goats [43].
Also, Gholam Ali Kojouri et al. studied the effect of some selenium types, such as sodium selenite and nano-size selenium on iron (Fe) homeostasis and the expression of transferrin and its receptor-binding protein genes on sheep for 20 days. The results of this study showed that serum iron concentration decreased in the beginning to the middle stages of the experiment, TIBC level increased and the expression of transferrin and its receptor genes significantly increased during the experimental period in both groups [44]. In addition, the authors reported selenium nanoparticles as having a stronger stimulatory effect on intracellular activities in another article. Particularly, they have compared the effect of nano-size selenium and sodium selenite on characteristics of neutrophils in sheep for 30 days.
However, nano-size selenium supplemented sheep dramatically increased the chemotactic and respiratory burst activities than the sodium selenite supplemented group [13]. The antioxidant properties of selenium related to its several genes, which include SEPP1, SEP15, SELENBP1, CAT, TRXNRD1-2, PRDX1-6, GPx, and SOD [45]. The glutathione peroxidase neutralizes hydrogen peroxide and organic hydroperoxides in the intracellular and extracellular compartments. Especially, the main activity of 1, 2, and 3 types is to protect against oxidative damages, antioxidants in plasma, and to reduce lipid hydro peroxidase. Shi et al. studied the antioxidant effect of inorganic, organic, and elemental nano-size selenium in growing weaned TAIHANG strain black male goats for 90 days. They determined the body weight (BW), average daily gain (ADG), serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) activity, and selenium concentration. The final BW increased (P<0.05), and selenium concentration of whole blood, serum and tissue, and serum antioxidant activity were affected in all selenium supplemented group as compared to the unsupplemented group. Also ADG was greater (P<0.05) in nano-size selenium and Seyeast supplemented groups. In addition, serum GSH-Px, SOD, and CAT were higher (P < 0.05) in nano-size selenium supplemented group than in the supplemented groups with sodium selenite and Se-yeast. Se level of whole blood, serum, and some organs were higher in only nano-size selenium supplemented group [3].
Another study by Sirous Sadeghian et al. reported the effects of nano-size selenium (orally 1 mg kg -1 body weight) and sodium selenite (orally 1 mg kg -1 -Se body weight) on the activity of neutrophils and hematological parameters in sheep for 30 days. The level of thiobarbituric acid reactive substances (TBARS) in plasma was significantly higher (P<0.05) in both selenium added groups than the control group. While white blood cell (WBC) count significantly increased in the nano-size selenium supplemented group, but the packed cell volume (PCV) and red blood cell (RBC) count were not significantly different in all groups. But in the nano-size Proceedings of the Mongolian Academy of Sciences PMAS selenium supplemented group, WBC was significantly higher on days 20 and 30, and for sodium selenite supplemented group WBC increased significantly just in 20 days. The neutrophil counts had significantly increased and the lymphocyte counts significantly decreased on 10 days in only nano-size selenium supplemented groups, and on days 20 and 30 in both selenium supplemented groups compared to the control group [46]. Selenium poisoning occurs if the selenium level is very high in the feed, soil, pasture, and water, and if the selenium level is very low is in them, selenium deficiency occurs in both humans and animals. It mostly occurs in ruminants especially kids, lambs, and calves, which is called white muscle disease (WMD) or nutritional myopathy in Veterinary Science. Many scientists have reported about it, namely, Muller et al. recorded that a low and deficient dietary selenium concentration are prone to many problems, including white muscle disease in lambs and calves, calf pneumonia, infertility, and exudative diathesis in chickens and other animals [47].
Actually, selenium bioavailability varies depending on several factors such as chemical forms, solubility, other dietary components, physiological status of the body [48]. Therefore, selenium concentration in whole blood, daily uptake (dosage), and chemical type are very important. Food supplement containing a suitable dose and the suitable type of selenium, especially elemental type, affects many of the above physiological functions and prevents many risks. Some studies have indicated to the blood selenium amount and daily intake value. For example; The Diagnostic Center for Population and Animal Health of Michigan State University determined the whole blood selenium concentration of ruminants, including sheep (lambs-adults) 120-350 ng/ml, goats (kidsadults) 170-300 ng/ml, and cattle (calves till 30 days-adults) 100-300 ng/ml. And for daily intake of selenium, National Research Council recommended 100 μg•kg −1 dry matter for beef cattle and calves, 300 μg•kg −1 dry matter [49] for dairy cattle, and 0.1-0.2 mg•kg −1 dry matter [50] for sheep. For goats, the recommended daily intake is 0.1 mg•kg −1 dry matter of feed [51].

CONCLUSIONS
Selenium nanoparticles are a good additive material for the functionalization of feed supplements. The systematic consumption of selenium nanoparticles and enriched feed supplements can increase the productivity of ruminants, also they can protect them from some disorders. It is reported that selenium absorption is much lower in ruminants than in monogastric animals. However, the study of nano-sized selenium absorption has not been completed. Therefore, the studies of feed supplement with selenium nanoparticles and their application, bioavailability, absorption, and accumulation for ruminants are needed to be continued in the future.