Effect of Organic Selenium Supplementation on the Antioxidant Status, Immune Response, and the Relative Expression of IL-2 and IFN-γ Genes in Ewes During the Hot Season.

This study was conducted to evaluate the effects of different doses of selenium (Se) from Sel-Plex© (selenium-enriched Saccharomyces cerevisiae yeast) supplement on the antioxidant status, the antibody titers against the foot-and-mouth disease virus, and the expression of interleukin-2 (IL-2) and interferon-γ (IFN-γ) genes in ewes during the hot season. Six ewes were kept at 25 °C and received basal diet (the negative control group), and 24 ewes were kept at 38 °C for 5 h per day and received no supplement (the positive control), 0.15, 0.30, and 0.45 mg Se/kg. Ewes in the positive control had higher (P<0.001) liver enzyme activity, malondialdehyde (MDA), and cortisol levels, and lower antibody titer than the negative control. The liver enzymes' lowest (P<0.001) activities were observed in ewes receiving 0.30 and 0.45 mg Se/kg. Ewes receiving 0.30 and 0.45 mg Se/kg had lower MDA levels than other treatments. Ewes receiving 0.30 and 0.45 mg Se/kg had higher (P<0.001) total antioxidant capacity levels than those receiving 0.15 mg Se/kg and the positive control. Se-supplemented groups had lower (P<0.001) relative expression of IL-2 and higher (P<0.04) expression of IFN-γ than the positive control. The antibody titer was the same in the positive control and the group receiving 0.15 mg Se/kg. Ewes fed a diet with 0.30 and 0.45 mg Se/kg had higher (P<0.011) antibody titer than the positive control. The Se supplementation can reverse the decrease of antioxidant capacity and immune function caused by heat stress, and 0.3 mg Se/kg from Sel-Plex©is the best dose.

New insights on selenoproteins and neuronal function.

Fifty years have passed since the discovery of the first selenoprotein by Rotruck and colleagues. In that time, the essential nature of selenium has come to light including the dependence of the brain on selenium to function properly. Animal models have shown that a lack of certain selenoproteins in the brain is detrimental for neuronal health, sometimes leading to neurodegeneration. There is also potential for selenoprotein-mediated redox balance to impact neuronal activity, including neurotransmission. Important insights on these topics have been gained over the past several years. This review briefly summarizes the known roles of specific selenoproteins in the brain while highlighting recent advancements regarding selenoproteins in neuronal function. Hypothetical models of selenoprotein function and emerging topics in the field are also provided.

Advances in the Study of the Mechanism by Which Selenium and Selenoproteins Boost Immunity to Prevent Food Allergies.

Selenium (Se) is an essential micronutrient that functions in the body mainly in the form of selenoproteins. The selenoprotein contains 25 members in humans that exhibit a number of functions. Selenoproteins have immunomodulatory functions and can enhance the ability of immune system to regulate in a variety of ways, which can have a preventive effect on immune-related diseases. Food allergy is a specific immune response that has been increasing in number in recent years, significantly reducing the quality of life and posing a major threat to human health. In this review, we summarize the current understanding of the role of Se and selenoproteins in regulating the immune system and how dysregulation of these processes may lead to food allergies. Thus, we can explain the mechanism by which Se and selenoproteins boost immunity to prevent food allergies.

Role for Selenium in Metabolic Homeostasis and Human Reproduction.

Selenium (Se) is a micronutrient essential for life. Dietary intake of Se within the physiological range is critical for human health and reproductive functions. Selenium levels outside the recommended range have been implicated in infertility and variety of other human diseases. However, presently it is not clear how different dietary Se sources are processed in our bodies, and in which form or how much dietary Se is optimum to maintain metabolic homeostasis and boost reproductive health. This uncertainty leads to imprecision in published dietary guidelines and advice for human daily intake of Se and in some cases generating controversies and even adverse outcomes including mortality. The chief aim for this review is to describe the sources of organic and inorganic Se, the metabolic pathways of selenoproteins synthesis, and the critical role of selenprotenis in the thyroid gland homeostasis and reproductive/fertility functions. Controversies on the use of Se in clinical practice and future directions to address these challenges are also described and discussed herein.

The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Toxicology and pharmacology of synthetic organoselenium compounds: an update.

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.

Chitosan-stabilized selenium nanoparticles alleviate cardio-hepatic damage in type 2 diabetes mellitus model via regulation of caspase, Bax/Bcl-2, and Fas/FasL-pathway.

The present study was carried out to explore a novel strategy with the hypothesis that the combined treatment with standard antidiabetic drug metformin (MET) and chitosan stabilized nanoparticles (CTS-Se-NPs) may have a potential role on insulin level, hepatic damage and apoptosis, and cardiac injury markers of type 2 diabetes mellitus (T2DM) in rat model. T2DM was induced by a high fat diet (HFD) for 8 weeks and a single injection of a low dose streptozotocin (STZ) (35 mg/kg) in Sprague Dawley rats. A total number of one hundred rats were divided into five groups; the first served as a control (non-diabetic) group and the other four groups served as diabetic rats. The treatments were even mono or combined therapy by CTS-Se-NPs and/or MET for 8 weeks. A group was given only MET (500 mg/kg bw/day), another was administered only CTS-Se-NPs at a dose of 2 mg se/kg/day, while the last group was given both of them (co-treated group). Biochemical, molecular and histopathological analyses were conducted to figure out the efficiency of the treatment by the monotherapeutic mode or combination therapy on the insulin level, oxidants/antioxidants status, inflammatory mediators, hepatic and cardiac injury biomarkers and apoptotic/anti-apoptotic gene expressions. Our results indicated that HFD/STZ-induced toxic effects on the serum, hepatic and cardiac tissues including a remarkable elevation of the oxidative and inflammatory mediators, and up-regulation of the apoptotic genes (Bax, Caspase-3, Fas, Fas-L) expression. Histologically, the heart tissue revealed various degenerative, vascular and inflammatory alterations characteristic to murine cardiomyopathy. Besides, livers from HFD-STZ-treated rats showed numerous cytotoxic, circulatory and inflammatory alterations. Combined therapy with MET and CTS-Se-NPs resulted in a better remarkable anti-diabetic effect demonstrated by substantial decreases in fasting blood glucose and insulin levels, and elevated with up-regulation of anti-apoptotic gene (BCL-2) and down-regulation of apoptotic genes after 8 weeks of treatment than that revealed in the monotherapeutic strategy. In addition, it ameliorated the damage of cardiac and hepatic tissues and reduced lipid accumulation, and pro-inflammatory cytokines levels and restored the antioxidant capacity. It could be concluded that, the combined strategy applied in the current study have a potential role to limit the diabetic complications and restore insulin resistance to a higher extent than monotherapeutic strategy and could be considered a promising therapeutic alternative in T2DM rat model.

The importance of selenium and zinc deficiency in cardiovascular disorders.

Cardiovascular diseases often linked with lifestyle are among the main causes of death, especially in the elderly population. The role of trace elements in health and disease has been emphasized in multiple scientific research. Moreover, supplementation of trace elements to improve health is becoming increasingly popular. The following paper presents current views on the relationship between the concentration of trace elements such as selenium and zinc in the body, as well as morphology and function of the cardiovascular system. Research discussing the effect of selenium and zinc supplementation on the function of the heart and blood vessels was also reviewed. The relationship between selenium and zinc concentration and morphology and function of the cardiovascular system is equally unclear, and therefore there is currently no scientific evidence for its supplementation for preventing cardiovascular diseases. It seems justified to continue scientific research on this subject due to the small number of experimental studies available on the topic of selenium and zinc deficiency and their impact on the cardiovascular system.

The Role of Selenium Mineral Trace Element in Exercise: Antioxidant Defense System, Muscle Performance, Hormone Response, and Athletic Performance. A Systematic Review.

Exercise overproduces oxygen reactive species (ROS) and eventually exceeds the body's antioxidant capacity to neutralize them. The ROS produce damaging effects on the cell membrane and contribute to skeletal muscle damage. Selenium (Se), a natural mineral trace element, is an essential component of selenoproteins that plays an important role in antioxidant defense. The activity of the enzyme glutathione peroxidase (GPx), a highly-efficient antioxidant enzyme, is closely dependent on the presence of Se. These properties of Se may be potentially applicable to improve athletic performance and training recovery. We systematically searched for published studies to evaluate the effectiveness of Se supplementation on antioxidant defense system, muscle performance, hormone response, and athletic performance among physically active individuals. We used the Preferred Reporting Elements for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and searched in SCOPUS, Web of Science (WOS), and PubMed databases to identify published studies until March 2020. The systematic review incorporated original studies with randomized controlled crossover or parallel design in which intake of Se administered once a day was compared with the same placebo conditions. No exclusions were applied for the type of physical exercise performed, the sex, nor the age of the participants. Among 150 articles identified in the search, 6 met the criteria and were included in the systematic review. The methodological quality of the studies was evaluated using the McMaster Critical Review Form. Oral Se supplementation with 180 µg/day or 240 µg/day (selenomethionine) and 200 µg/day (Sodium Selenite), significantly decreased lipid hydroperoxide levels and increased GPx in plasma, erythrocyte, and muscle. No significant effects were observed on athletic performance, testosterone hormone levels, creatine kinase activity, and exercise training-induced adaptations on oxidative enzyme activities or on muscle fiber type myosin heavy chain expression. In addition, Se supplementation showed to have a dampening effect on the mitochondria changes in chronic and acute exercise. In summary, the use of Se supplementation has no benefits on aerobic or anaerobic athletic performance but it may prevent Se deficiencies among athletes with high-intensity and high-volume training. Optimal Se plasma levels may be important to minimize chronic exercise-induced oxidative effects and modulate the exercise effect on mitochondrial changes.

The Role of Selenium in Health and Disease: Emerging and Recurring Trends.

In this Special Issue of Nutrients, "The Role of Selenium in Health and Disease" covers diverse diseases in the 8 original research articles and 2 reviews, such as cardiovascular disorders (CVD), metabolic syndrome, obesity, cancer, and viral infection, and highlights novel potential biomarkers of disease risk and prognosis [...].

Oxidative Stress in Autism Spectrum Disorder.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

Selenium and Neurological Diseases: Focus on Peripheral Pain and TRP Channels.

Pain is a complex physiological process that includes many components. Growing evidence supports the idea that oxidative stress and Ca2+ signaling pathways participate in pain detection by neurons. The main source of endogenous reactive oxygen species (ROS) is mitochondrial dysfunction induced by membrane depolarization, which is in turn caused by Ca2+ influx into the cytosol of neurons. ROS are controlled by antioxidants, including selenium. Selenium plays an important role in the nervous system, including the brain, where it acts as a cofactor for glutathione peroxidase and is incorporated into selenoproteins involved in antioxidant defenses. It has neuroprotective effects through modulation of excessive ROS production, inflammation, and Ca2+ overload in several diseases, including inflammatory pain, hypersensitivity, allodynia, diabetic neuropathic pain, and nociceptive pain. Ca2+ entry across membranes is mediated by different channels, including transient receptor potential (TRP) channels, some of which (e.g., TRPA1, TRPM2, TRPV1, and TRPV4) can be activated by oxidative stress and have a role in the induction of peripheral pain. The results of recent studies indicate the modulator roles of selenium in peripheral pain through inhibition of TRP channels in the dorsal root ganglia of experimental animals. This review summarizes the protective role of selenium in TRP channel regulation, Ca2+ signaling, apoptosis, and mitochondrial oxidative stress in peripheral pain induction.

Selenium Mitigates Cadmium-Induced Adverse Effects on Trace Elements and Amino Acids Profiles in Chicken Pectoral Muscles.

Cadmium (Cd), as one of the most toxic heavy metals, has become a widespread environmental contaminant and threats the food quality and safety. The protective effect of selenium (Se) on Cd-induced tissue lesion and cytotoxicity in chicken has been extensively reported. The objective of this study was to investigate the antagonistic effect of Se on Cd-induced damage of chicken pectoral muscles via analyzing the trace elements and amino acids profiles. Firstly, 19 trace elements contents were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that under Cd exposure, the contents of Cd, lead (Pb), mercury (Hg), aluminum (Al), and lithium (Li) were significantly elevated, and the contents of Se, iron (Fe), and chromium (Cr) were significantly reduced. However, supplementing Se significantly reversed the effects induced by Cd. Secondly, the amino acids contents were detected by L-8900 automatic amino acid analyzer. The results showed that supplementing Se increased significantly Cd-induced decrease of valine (Val), leucine (Leu), arginine (Arg), and proline (Pro). Thirdly, the results of principal component analysis (PCA) showed that cobalt (Co), manganese (Mn), silicium (Si), and Pro may play special roles in response to the process of Se antagonizes Cd-induced damage of pectoral muscles in chickens. In summary, these results indicated that different trace elements and amino acids possessed and exhibited distinct responses to suffer from Se and/or Cd in chicken pectoral muscles. Notably, Se alleviated Cd-induced adverse effects by regulating trace elements and amino acids profiles in chicken pectoral muscles.

Selenium and selenoproteins: from endothelial cytoprotection to clinical outcomes.

The role of the vascular endothelium in inflammation was demonstrated experimentally through biomarkers of endothelial dysfunction and cytoprotection. Selenium is a trace element essential for cell protection against oxidative lesions triggered by reactive oxygen species or inflammatory responses. Preclinical studies have demonstrated a relationship between adhesion molecules as biomarkers of endothelial dysfunction and selenoproteins as biomarkers of selenium status under conditions that mimic different diseases. Most studies in humans indicate an association between selenium deficiency and increased risk of morbidity and mortality, yet the pathophysiology of selenium in endothelial activation remains unknown. Here, we summarize selenium-dependent endothelial function evaluation techniques and focus on the role of selenium in endothelial cytoprotection according to current scientific knowledge. Most studies on the role of selenium in endothelial processes show selenium-dependent endothelial functions and explain how cells and tissues adapt to inflammatory insults. Taken together, these studies show an increase in adhesion molecules and a decrease in the expression of selenoproteins following a decreased exposure to selenium. Few clinical trials have enough methodological quality to be included in meta-analysis on the benefits of selenium supplementation. Furthermore, the methodology adopted in many studies does not consider the relevant findings on the pathophysiology of endothelial dysfunction. Preclinical studies should be more frequently integrated into clinical studies to provide clearer views on the role of selenium status in endothelial cytoprotection.

Disruption of selenium transport and function is a major contributor to mercury toxicity in zebrafish larvae.

Mercury is one of the most toxic elements threatening the biosphere, with levels steadily rising due to both natural and human activities. Selenium is an essential micronutrient, required for normal development and functioning of many organisms. While selenium is known to counteract mercury's toxicity under some conditions, to date information about the mercury-selenium relationship is fragmented and often controversial. As part of a systematic study of mercury and selenium interactions, zebrafish (Danio rerio) larvae (a model verterbrate) were exposed to methylmercury chloride or mercuric chloride. The influence of pre- and post-treatment of selenomethionine on the level and distribution of mercury and selenium in the brain and eye sections, as well as on toxicity, were examined. Selenomethionine treatment decreased the amount of maternally transfered mercury in the larval brain. Selenomethionine treatment prior to exposure to mercuric chloride increased both mercury and selenium levels in the brain but decreased their toxic effects. Conversely, methylmercury levels were not changed as a result of selenium pre-treatment, while toxicity was increased. Strikingly, both forms of mercury severely disrupted selenium metabolism, not only by depleting selenium levels due to formation of Hg-Se complexes, but also by blocking selenium transport into and out of tissues, suggesting that restoring normal selenium levels by treating the organism with selenium after mercury exposure may not be possible. Disruption of selenium metabolism by mercury may lead to disruption in function of selenoproteins. Indeed, the production of thyroid hormones by selenoprotein deiodinases was found to be severely impaired as a result of mercury exposure, with selenomethionine not always being a suitable source of selenium to restore thyroid hormone levels.

Effect of a single-dose parenteral selenium supplement administered to pregnant dairy cows on selenium and iron concentrations and immune status of calves.

The study was performed on 21 H-F calves divided into 3 groups of 7 animals each. The first group was composed of calves whose mothers did not receive an injection of Se preparation. The second and third groups consisted of calves whose mothers were administered injections of Se and vitamin E in a single dose of 10 ml and 30 ml, 10 days before the expected parturition date. 24 hours after birth, blood samples were collected from all calves to determine Se, Fe and IgG concentrations and the activity of GSH-Px and GGT. The results of the study indicate that the administration of a single-dose Se supplement to cows in late pregnancy increases Se concentration in calves and promotes passive transfer of immunity from the mother to offspring.

Selenium at the redox interface of the genome, metabolome and exposome.

Selenium (Se) is a redox-active environmental mineral that is converted to only a small number of metabolites and required for a relatively small number of mammalian enzymes. Despite this, dietary and environmental Se has extensive impact on every layer of omics space. This highlights a need for global network response structures to provide reference for targeted, hypothesis-driven Se research. In this review, we survey the Se research literature from the perspective of the responsive physical and chemical barrier between an organism (functional genome) and its environment (exposome), which we have previously termed the redox interface. Recent advances in metabolomics allow molecular phenotyping of the integrated genome-metabolome-exposome structure. Use of metabolomics with transcriptomics to map functional network responses to supplemental Se in mice revealed complex network responses linked to dyslipidemia and weight gain. Central metabolic hubs in the network structure in liver were not directly linked to transcripts for selenoproteins but were, instead, linked to transcripts for glucose transport and fatty acid ß-oxidation. The experimental results confirm the survey of research literature in showing that Se interacts with the functional genome through a complex network response structure. The results imply that systematic application of data-driven integrated omics methods to models with controlled Se exposure could disentangle health benefits and risks from Se exposures and also serve more broadly as an experimental paradigm for exposome research.

Effects of ultrasound and selenium on human neurons in vitro.

As the effects of ultrasound on human brain functions might bear therapeutic potential, in this study, we examined the effects of diagnostic, i.e. non-thermal, ultrasound, on morphology, networking, and metabolic activity of SH- SY5Y human neurons in culture, as well as on the expression of GAP-43, Hsp90 and VEGF proteins, with and without selenium in the culture medium. The rationale for studying selenium lays in the observation that selenium improves functional neurologic outcome in traumatic brain injury and, therefore, analysis of the interactions between ultrasound and selenium may be of clinical interest. In the presence of selenium, ultrasound increased the overall number and length of elongations arising from the neuron bodies, thus reflecting an increase in the complexity of neuronal networks and circuits. The expression of GAP-43, Hsp90 and VEGF and metabolic activity of SH-SY5Y neurons, studied as markers of cell damage, were not affected by ultrasound or selenium. This study suggests that ultrasound may modulate neuronal networking in vitro without inducing cellular or molecular damage and highlights the potential role of selenium in the ultrasound-elicited cellular responses.

A Summary of New Findings on the Biological Effects of Selenium in Selected Animal Species-A Critical Review.

Selenium is an essential trace element important for many physiological processes, especially for the functions of immune and reproductive systems, metabolism of thyroid hormones, as well as antioxidant defense. Selenium deficiency is usually manifested by an increased incidence of retention of placenta, metritis, mastitis, aborts, lowering fertility and increased susceptibility to infections. In calves, lambs and kids, the selenium deficiency demonstrates by WMD (white muscle disease), in foals and donkey foals, it is associated with incidence of WMD and yellow fat disease, and in pigs it causes VESD (vitamin E/selenium deficiency) syndrome. The prevention of these health disorders can be achieved by an adequate selenium supplementation to the diet. The review summarizes the survey of knowledge on selenium, its biological significance in the organism, the impact of its deficiency in mammalian livestock (comparison of ruminants vs. non-ruminants, herbivore vs. omnivore) and possibilities of its peroral administration. The databases employed were as follows: Web of Science, PubMed, MEDLINE and Google Scholar.