Skip to main content

Toxicological effects of nanoselenium in animals


The productivity and sustainability of livestock production systems are heavily influenced by animal nutrition. To maintain homeostatic balance in the body of the animal at different phases of life, the percentage of organically active minerals in livestock feed must be optimized. Selenium (Se) is a crucial trace mineral that is required for the maintenance of many functions of the body. Se nanoparticles (SeNPs) attracted considerable interest from researchers for a variety of applications a decade ago, owing to their extraordinary properties. SeNPs offer significant advantages over larger-sized materials, by having a comparatively wider surface area, increased surface energy, and high volume. Despite its benefits, SeNP also has toxic effects, therefore safety concerns must be taken for a successful application. The toxicological effects of SeNPs in animals are characterized by weight loss, and increased mortality rate. A safe-by-strategy to certify animal, human and environmental safety will contribute to an early diagnosis of all risks associated with SeNPs. This review is aimed at describing the beneficial uses and potential toxicity of SeNPs in various animals. It will also serve as a summary of different levels of SeNPs which should be added in the feed of animals for better performance.


Recent years have witnessed a growing academic interest in nanotechnology development agriculture [1]. Inorganic nanoparticles (NPs) are fast becoming a prospective instrument in animal feed. They promise an improvement of properties of traditional mineral elements, through their biologic efficiency [2], bioavailability, or antimicrobial effects [3]. NPs are recognized as particles less than 100 nm in diameter, prepared by synthetic or biological ways. Previous studies have observed that NPs can maintain excellent bioavailability and decreased toxicity compared to inorganic and organic formulae of trace minerals [4]. The most frequently discussed mineral compound is selenium (Se) due to its narrow relationship between toxicity and necessity for organisms [5]. The biological efficacy of Se is based on its integration into the active center of 25 selenoproteins (SeLPs) [6] . Organic forms of Se and specific salts have been studied for many years [7], but elemental Se nanoparticles (SeNPs) have recently received a great deal of attention as a potential source of this vital component [8]. Figure 1 below illustrates the biological proceptivity and effects of SeNPs which have been experimentally observed.

Fig. 1
figure 1

The representation of some important biological prospects and effects of SeNPs

A few studies have shown that SeNPs have a lower toxic potency than dissolved ionic Se species, which is a promising finding [9]. The evidence suggests that Se from NPs becomes less bioavailable to some extent [10]. Furthermore, the toxicity of SeNPs could be reduced through green synthesis or modification. Numerous experiments of SeNPs toxicity have been conducted in animals, but proper knowledge about the toxicological effects of SeNPs is insufficient. This review is aimed to evaluate the updated information regarding the toxicological effects of SeNPs in animals.

Toxicity by selenium intake

Se poisoning is a threat in geographical areas with a high abundance of Se in the environment. Continuous intake of water or feed rich in Se can lead to its accumulation and selenosis in the body [11]. Acute Se poisoning of grazing animals occurs as a result of the consumption of a large number of accumulator plants with a high concentration of in a short period of time. For example, seleniferous plants include prince’s plume, astragalus and woody asters [12]. According to scientific evidence, all species of animals are vulnerable to Se toxicosis. Symptoms of Se poisoning in mammals vary widely and include nail abnormalities and loss of hair and wool [13], weakness, vomiting, diarrhea, tiredness, reduced cognitive function, lethargy, immobility, fatigue, weight loss, itchy skin and mucous membrane irritation [14]. Individuals who have the condition may experience lateral sclerosis as well as irritation in the pharynx and bronchial tubes, and may be recognized by a garlic smell on their breath and in their sweat [11].

On the biochemical level, Se toxicosis includes splenomegaly, anemia, liver damage, and elevated ratios of bilirubin respectively [15]. During the first 24 h after acute poisoning, Se concentrations in the kidneys and liver drop by 80% from peak levels, according to animal studies [14]. An examination of Se poisoning in domestic animals has shown that there was an increase in the rate of conception and the fetal resorption in bovine, sheep, and horses fed naturally organic Se-containing diets with 25–50 mg Se/kg [16] . Poisoning can also occur in swine, fish, and other grain-consuming species raised on seleniferous soils or, more often, due to errors in feed formulation [17].

Acute Se toxicity could lead to brain disorders, changes in mental status, gastrointestinal symptoms, breathing difficulty, hepatocellular necrosis, kidney failure, heart attacks, and other cardiac disorders. Some research has shown Se intoxication can delay the growth of animals [11]. Younger animals are more sensitive to Se poisoning and the chemical forms may lead to differences in toxicity [18]. In addition to mammals, Se has a wide range of harmful consequences in birds, and the onset of toxicity varies from several hours to days [19]. The toxic effects in avian species include mortality, decreased growth, histopathological abnormalities, and changes in hepatic glutathione (GSH) metabolism [20].

General mechanism of se toxicity

It has been shown that Se toxicity greatly depends on its form. Generally, organic Se compounds are known to be less hazardous to cells than selenite, when investigated both in vitro and in vivo [18]. Se species metabolize by several pathways into different chemical forms, or they are incorporated into selenoproteins. In addition, due to the chemical similarity of Se with Sulphur, Se can be involved in the biochemical pathways of thiol compounds. Scientific evidence shows Se can spontaneously interact with glutathione to form Se0, glutathiolseleol (GS-Se), selenodiglutathione (GS-Se-SG), hydrogen selenide (H2Se) [21] and selenotrisulfides. Selenotrisulfides can react with other thiols to produce superoxide and hydrogen peroxide, both of which are toxic [22]. In addition, Se exposure promotes redox imbalance and the production of reactive oxygen species in eucaryotic cells [11].

Mechanism of se induced genotoxicity

The genotoxicity of Se has been studied extensively. This genotoxicity occurs when an excess of ROS is present in cells and reacts with cellular components. This causes base lesions as well as breakage of deoxyribose nucleic acid (DNA) strands via its reaction with both deoxyribose sugars and the nucleobases of DNA. In addition, ROS oxidizes DNA, and Se interferes with DNA repair and transcriptional regulation, posing a threat to the stability of genetic information. Further, Se also interacts with some DNA repair proteins that contain functional zinc (Zn) finger motifs, which are associated with signaling pathways, such as DNA repair peptides, and DNA protein-protein interaction factors. Se can also interact with metallothionein and cause the release of Zn, which can affect DNA-binding capacity as well as genome stability [23]. Several authors have proposed that Se causes genotoxicity by communicating with thiol groups by these means. On the other hand, it was discovered that the number of dicentric chromosomes is roughly 2 times higher in Se-plus radiation exposure treatment compared to the control group [24]. In addition, Se causes genotoxicity by interfering with the ataxia-telangiectasia mutated gene and protein 53 expressions in the body. It have been shown that mice treated with methylselenic acid and methyl selenocysteine in ten days treatment delaying in the disease’s progression by increasing apoptosis and decreasing proliferation was observed [21].

Mechanism of se induced cytotoxicity

Many researchers have investigated the cytotoxicity of Se, which causes irreversible changes in cells through a variety of mechanisms. It has been found when cells are exposed to Se, the production of ROS can increase. Also, Se induces the production of ROS as a result of the selenide (Se2−) reaction with thiol groups [25]. Excess ROS damages not only lipids and proteins but also mitochondrial membrane potential. According to one study, ROS-induced oxidative stress results from the activation of the mitochondrial apoptotic pathway [26]. It has long been known that ROS causes cytotoxicity by activating c-Jun N-terminal kinases (JNK), a subgroup of mitogen-activated protein kinases that regulates a wide range of cellular functions including cell proliferation, differentiation, and apoptosis. ROS can stimulate the JNK-mediated tumor necrosis factor [27]. ROS can also act as signal transduction pathway modulators, which can impact a variety of biological processes such as cell growth, apoptosis, and cell adhesion, among others [28]. It has been discovered that Se, a constituent of SelPs, seems to have a close relationship with redox potential, which can cause cytotoxicity by altering thioredoxin reductase (TrxR). This altered TrxR, when combined with thioredoxin (Trx), forms a potent dithiol-disulphide oxidoreductase system [29]. In addition to binding to signaling molecules (including apoptosis signal-regulating kinase-1 and Trx interacting protein), the system can also regulate cell growth by interacting with the cells’ growth and survival mechanisms. Glutaredoxin proteins, which are redox-active proteins, have been associated with susceptibility to Se cytotoxicity by limiting intracellular cystine levels, according to another research group [30]. As Se can modulate cell signaling pathways through the use of a thiol redox system, it causes cytotoxicity through the production of ROS, as well as by affecting the expression of correlating genes and proteins [31].

The toxic effects of SeNPs

Various animal species have different sensitivities to the effects of Se and SeNPs. The toxicity of nanoparticles has mainly been studied in aquaculture due to these species’ sensitivity to water pollutants. The toxicity of SeNPs in aquaculture has been well documented and reviewed in recent studies. According to a review article by Abbas et al., it has been implied that the nanoforms of Se are particularly toxic compared to inorganic Se salts [32]. This finding is alarming in that most of the nanomaterials used, including SeNPs, accumulate in the environment and can reach fish that subsequently bioaccumulate SeNPs in large quantities. In contradiction, however, it has also been reported that the SeNPs can increase the productivity of aquatic animals and improve their health in controlled experiments [33]. Similar to the effect in mammals, the toxicological effect in fish depends on the dose, the chemistry of the SeNPs, and the exposure time. Regarding the toxicity of SeNPs, this section reviews the literature on toxicological studies of SeNPs. The findings are summarized in Table 1. To compare SeNPs effect on the mammalian organisms the chemoprotective studies of SeNPs are included in the Table 2. It is apparent, the SeNPs effects on organism are greater than inorganic Se forms. In addition, the impact of Se on the health status depends on individual need to create antioxidant defence. Otherwise, an excess of Se leads to its toxicity. The toxicity of SeNPs has been thought to be related to Se toxicity in general. At higher concentration, both Se and SeNPs have pro-oxidative properties leading to ROS production [34]. This effect could be enhanced by the bioaccumulation effect in several tissues where the liver is most sensitive.

Table 1 Summary of toxicologic studies of SeNPs in various mammalian species
Table 2 Summary of original research articles focusing on the chemoprotective effect of SeNPs on various mammalian species

This area for the toxicological evaluation of SeNPs have mainly focused only on antioxidant system performance, body weight, and bioaccumulation in the liver, kidney and heart. There is a paucity of literature on the interaction of SeNPs with the immune system, gastrointestinal tract, immune system, or bioaccumulation in muscles and other indirect targets of Se. Due to a large surface area and small size, SeNPs and many other types of nanoparticles seem to be more reactive and show better biodistribution in organisms compared to other forms of Se. Some studies described below have examined the molecular mechanism of toxicity induced by SeNPs, as well as the comparison of acute and long-term toxicity.

Most studies that have compared the toxicity of Se and SeNPs both agree well with the lower toxicity of SeNPs. Sublethal doses of 20 nm SeNPs at doses of 0.05, 0.5, or 4 mg Se/kg body weight (BW)/d had no adverse effect on brain neurotransimeters or hematological parameters in rats compared to control and sodium selenite-treated groups group (0.5 mg Se/kg body weight/d) in a 28-day trial [35]. In similar research, low doses of SeNPs did not cause harmful effect during 48 days of treatment in rabbits. Both SeNPs and sodium selenite showed no significant changes in blood biochemistry and liver enzyme activity at a dose of 0.3 mg/kg BW. Only liver PGx and T-AOC activity were increased in Se-treated groups compared to the control group. Biochemical analysis was supported by higher GPX-1 mRNA expression of 195% for Nano-Se and 154% for sodium selenite [36]. Higher doses of 2.0, 4.0 and 8.0 mg Se/kg body weight of SeNPs administered for 14 d caused increased body weight, increased liver enzymes (ALT, AST) and cholesterol. Histopathological findings showed lesions in the liver, kidneys, lungs and thymus gland. The presence of apoptotic cells was also observed, indicating that doses greater than 2 mg Se/kg BW induced chronic toxicity [37]. Similar findings were found in male rats treated with SeNPs at doses of 2, 4 and 8 mg Se/kg body weight for two weeks. Administration of SeNP above 4.0 mg Se/kg body weight decreased antioxidant capacities in the liver heart, and blood serum, and downregulated mRNA expression of GPX1 and GPX4 in the liver. The proposed mechanism of SeNPs toxicity was further demonstrated in buffalo rat liver cell lines. SeNPs at a concentration of 24 mol/L decreased cell viability and damaged antioxidant capacity. The decrease in cell viability induced by SeNPs was mainly due to apoptosis but not cell necrosis [38]. A comprehensive toxicological study showed that the 20–60 nm SeNPs and Se-methionine in supranational amounts (30 and 70 μg Se/kg BW) improved the Se accumulation in whole blood, liver and kidney in a dose-dependent manner compared to the control. At the dietary level of Se (1000 mg Se/kg BW), no improving effect of bioaccumulation in blood and tissues was observed in the case of SeNPs but not in Se-methionine form. No difference was observed between Se-methionine and SeNPs with regard to GPx activity in plasma, liver and kidneys. However, compared to Se-Met, SeNPs showed lower toxicity (LD50 92.1 mg/Se/kg for Se-Met and 14.6 mg/Se/kg for SeNPs) and fewer markers of acute liver injury. A reduced accumulation of Se in dietary amounts and a higher lethal dose in mice fed SeNPs confirms the possibility of using SeNPs to avoid Se toxicity [39]. The proposed mechanism works via different absorption of Se by cells and their phase 2 response [40].

While SeNPs have shown variable toxicological outcomes, bionically or green synthesized and modified NPs have been reported which improving the effect on model animal health and reduce toxicity. The main advantage of bionic NPs appears to be the mechanism of their synthesis, which leads to the enrichment of SeNPs with bioactive compounds. Because of this ability, bionic SeNPs have unique properties. The advantages of bionic and green synthesized NPs have been well-documented in several review articles [41]. To be specific for SeNPs, the comparative study of Shakibaie et al. [53] was introduced. SeNPs (20,200 nm) were isolated from Bacillus sp. and orally administered to rats at doses of 2.5, 5, 10 and 20 mg Se/kg BW for 14 d. Compared to SeO2, bionic SeNPs showed a 26-fold lower LD50, while no harmful effects on the organism were observed at a lower dose [40]. Not only are bionic NPs able to reduce the toxic effect, but surface modifications make it possible to reduce the Se reactivity. κ-carrageenan-capped SeNPs (6.8 and 24.5 nm) at a dose of 2 mg/kg BW did not cause visible macroscopic or microscopic damage to major internal organs and systems in mice. However, an increased bioaccumulation of 6.8 nm SeNPs was found in liver, kidney and brain. Further experiments within the same study showed a size-dependent antioxidant activity of SeNPs, while smaller SeNPs showed a higher ability to scavenge free radicals ABTS and DPPH. These results clarified that not only the size of SeNPs might play a role in Se bioaccumulation, but their reactivity allows them to participate in biochemical interactions with organic compounds [42]. However, the vast majority of researchers have not considered the long-term toxicity of SeNPs. To illustrate, in Xiao’s study, the first experiment showed an enhancing effect of SeNPs (50 g Se/kg/d) in ApoE−/− mice in an 8-week experiment [43]. In another 24-week experiment, SeNP supplementation eliminated atherosclerotic lesions and increased antioxidant stress by inhibiting antioxidant enzymes. In addition, metabolic liver damage and hyperlipidemia have been observed. The negative effects were also size dependent, possibly due to cellular uptake. Nevertheless, the long-term toxicity of SeNPs was still lower than that of sodium selenite [44].

In general, therefore, it appears that the toxicity of SeNPs is a function of several interrelated parameters such as nanoparticle size and chemistry of the SeNP, dose, and exposure time that affect the biological response of the organism. The results of toxicological studies have shown that the main targets of the toxicity of SeNPs are not only prooxidative properties, but also their interactions with metabolic pathways and molecular signaling pathways, including apoptotic pathways, the ability of small nanoparticles to penetrate various tissues, and the organism’s ability to enzymatic transformation and eliminate Se.


SeNPs and Se species have very similar mechanisms of action and toxicity. The biggest differences in their action are due to their size and different reactivity. SeNPs are more bioavailable due to their small size, and according to some studies have greater antioxidant potential. Toxicological studies indicate that they are less toxic than sodium selenite. However, in research articles dealing with chemoprotective effects, SeNPs always appear to have improving effect at lower concentrations compared to sodium selenite. These findings could implicate that the effect of SeNPs depends on the individual saturation of the selenium-treated organism.

Availability of data and materials

The manuscript does not contain any experimental data.



Bovine serum albumin


Deoxyribose nucleic acid


Growth hormone




Glutathione peroxidase


Glutathione S-transferase


Insulin growth-like factor axis


Insulin growth like factor type 1 receptor


Immunoglobulin G

IgM :

Immunoglobulin M



Na2SeO3 :

Sodium selenite


Nano meter







Se2− :







Selenium nanoparticles


Se-enriched yeast


Superoxide dismutase




  1. Duhan JS, Kumar R, Kumar N, Kaur P, Nehra K, Duhan S. Nanotechnology: the new perspective in precision agriculture. Biotechnol Rep. 2017;15:11–23.

    Article  Google Scholar 

  2. De M, Ghosh PS, Rotello VM. Applications of nanoparticles in biology. Adv Mater. 2008;20(22):4225–41.

    Article  CAS  Google Scholar 

  3. Wang L, Hu C, Shao L. The-antimicrobial-activity-of-nanoparticles--present-situati. Int J Nanomedicine. 2017;12:1227–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int J Nanomedicine. 2017;12:1227–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Livingstone MBE, Black AE. Biomarkers of nutritional exposure and nutritional status. J Nutr. 2003;133(3):895S–920S.

    Article  CAS  PubMed  Google Scholar 

  6. Papp LV, Holmgren A, Khanna KK. Selenium and selenoproteins in health and disease. Antioxid Redox Signal, vol. 12. New York: Mary Ann Liebert, Inc.; 2010. p. 793–5.

  7. Nogueira CW, Zeni G, Rocha JBT. Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev. 2004;104(12):6255–85.

    Article  CAS  PubMed  Google Scholar 

  8. Ikram M, Javed B, Raja NI, Mashwani Z-U-R. Biomedical potential of plant-based selenium nanoparticles: a comprehensive review on therapeutic and mechanistic aspects. Int J Nanomedicine. 2021;16:249–68.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bisht N, Phalswal P, Khanna PK. Selenium nanoparticles: a review on synthesis and biomedical applications. Mater Adv Royal Soc Chem. 2022;3(3):1415–31.

    Article  CAS  Google Scholar 

  10. Lin X, Wang L, Zhao J, He L, Cui L, Gao Y, et al. Nanosafety evaluation through feces: a comparison between selenium nanoparticles and selenite in rats. Nano Today. 2021;36:101010.

    Article  CAS  Google Scholar 

  11. Lv Q, Liang X, Nong K, Gong Z, Qin T, Qin X, et al. Advances in research on the toxicological effects of selenium. Bull Environ Contam Toxicol. 2021;106:715–26.

    Article  CAS  PubMed  Google Scholar 

  12. Saha U, Fayiga A, Hancock D, Sonon L. Selenium in animal nutrition: deficiencies in soils and forages, requirements, supplementation and toxicity. Int J appl agric Sci. 2016;2(6):112–25.

    Article  Google Scholar 

  13. Mehdi Y, Hornick J-L, Istasse L, Dufrasne I. Selenium in the environment, metabolism and involvement in body functions. Molecules. 2013;18(3):3292–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nuttall KL. Evaluating selenium poisoning. Ann Clin Lab Sci. 2006;36:409–20.

    CAS  PubMed  Google Scholar 

  15. Levander OA, Morris VC, Ferretti RJ. Comparative effects of selenium and vitamin E in lead poisoned rats. J Nutr. 1977;107(3):378–82.

    Article  CAS  PubMed  Google Scholar 

  16. Harr JR, Muth OH. Selenium poisoning in domestic animals and its relationship to man. Clin Toxicol. 1972;5(2):175–86.

    Article  CAS  PubMed  Google Scholar 

  17. Fordyce FM. Selenium deficiency and toxicity in the environment. In: Selinus O, editor. Essentials of medical geology. Dordrecht: Springer; 2013. p. 375–416.

  18. Yang H, Jia X. Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: Acute toxicity, genotoxicity and subchronic toxicity. Regul Toxicol Pharmacol. 2014;70:720–7.

    Article  CAS  Google Scholar 

  19. Ohlendorf HM, Heinz GH. Selenium in Birds. In: Beyer WN, Meador JP, editors. Environmental contaminants in biota. Boca Raton: CRC Press; 2011. p. 669–702.

  20. Hoffman DJ. Role of selenium toxicity and oxidative stress in aquatic birds. Aquat Toxicol. 2002;57(1-2):11–26.

    Article  CAS  PubMed  Google Scholar 

  21. Sun H, Rathinasabapathi B, Wu B, Luo J, Pu L, Ma LQ. Arsenic and selenium toxicity and their interactive effects in humans. Environ Int. 2014;69:148–58.

    Article  CAS  Google Scholar 

  22. Lazard M, Dauplais M, Blanquet S, Plateau P. Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells. Biomol Concepts. 2017;8(2):93–104.

    Article  CAS  PubMed  Google Scholar 

  23. Monteith AJ, Skaar EP. The impact of metal availability on immune function during infection. Trends Endocrinol Metab. 2021;32(11):916–28.

    Article  CAS  PubMed  Google Scholar 

  24. Abul-Hassan KS, Lehnert BE, Guant L, Walmsley R. Abnormal DNA repair in selenium-treated human cells. Mutat Res Toxicol Environ Mutagen. 2004;565(1):45–51.

    Article  CAS  Google Scholar 

  25. Ali W, Zhang H, Junaid M, Mao K, Xu N, Rasool A, et al. Insights into the mechanisms of arsenic-selenium interactions and the associated toxicity in plants, animals, and humans: A critical review. Crit Rev Environ Sci Technol. 2020;51(7):704–50.

    Article  CAS  Google Scholar 

  26. Baregamian N, Song J, Papaconstantinou J, Hawkins HK, Evers BM, Chung DH. Intestinal mitochondrial apoptotic signaling is activated during oxidative stress. Pediatr Surg Int. 2011;27(8):871–7.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dwivedi P. ROS mediated apoptotic pathways in primary effusion lymphoma: Comment on induction of apoptosis by Shikonin through ROS-mediated intrinsic and extrinsic pathways in primary effusion lymphoma. Transl Oncol. 2021;14(7):101061.

  28. Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48(6):749–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wischhusen P, Larroquet L, Durand T, Oger C, Galano JM, Rocher A, et al. Oxidative stress and antioxidant response in rainbow trout fry exposed to acute hypoxia is affected by selenium nutrition of parents and during first exogenous feeding. Free Radic Biol Med. 2020;155:99–113.

    Article  CAS  PubMed  Google Scholar 

  30. Wilber CG. Toxicology of selenium: a review. Clin Toxicol. 1980;17(2):171–230.

    Article  CAS  PubMed  Google Scholar 

  31. Temple MD, Perrone GG, Dawes IW. Complex cellular responses to reactive oxygen species. Trends Cell Biol. 2005;15(6):319–26.

    Article  CAS  PubMed  Google Scholar 

  32. Abbas WT. Advantages and prospective challenges of nanotechnology applications in fish cultures: a comparative review. Environ Sci Pollut Res. 2021;28(7):7669–90.

  33. Dawood MAO, El Basuini MF, Yilmaz S, Abdel-Latif HMR, Kari ZA, Abdul Razab MKA, et al. Selenium nanoparticles as a natural antioxidant and metabolic regulator in aquaculture: a review. Antioxidants. 2021;10(9):1364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fernandes AP, Gandin V. Selenium compounds as therapeutic agents in cancer. Biochim Biophys Acta. 2015;1850(8):1642–60.

    Article  CAS  Google Scholar 

  35. Hadrup N, Loeschner K, Mandrup K, Ravn-Haren G, Frandsen HL, Larsen EH, et al. Subacute oral toxicity investigation of selenium nanoparticles and selenite in rats. Drug Chem Toxicol. 2019;42(1):76–83.

    Article  CAS  PubMed  Google Scholar 

  36. Qin F, Chen F, Zhao F, Jin T, Ma J. Effects of nanoselenium on blood biochemistry, liver antioxidant activity and GPx-1 mRNA expression in rabbits. In: International Conference on Biomedical and Biological Engineering. Atlantis Press; 2016. p. 166–71.

  37. He Y, Chen S, Liu Z, Cheng C, Li H, Wang M. Toxicity of selenium nanoparticles in male Sprague-Dawley rats at supranutritional and nonlethal levels. Life Sci. 2014;115(1-2):44–51.

    Article  CAS  PubMed  Google Scholar 

  38. Hosnedlova B, Kepinska M, Skalickova S, Fernandez C, Ruttkay-Nedecky B, Peng Q, et al. Nano-selenium and its nanomedicine applications: a critical review. Int J Nanomedicine. 2018;13:2107–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhang J, Wang X, Xu TT. Elemental selenium at nano size (Nano-se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice. Toxicol Sci. 2008;101(1):22–31.

    Article  CAS  PubMed  Google Scholar 

  40. Xiao H, Parkin KL. Induction of phase II enzyme activity by various selenium compounds. Nutr Cancer. 2006;55(2):210–23.

    Article  CAS  PubMed  Google Scholar 

  41. Mohammadinejad R, Karimi S, Iravani S, Varma RS. Plant-derived nanostructures: types and applications. Green Chem. 2015;18(1):20–52.

    Article  Google Scholar 

  42. Lesnichaya M, Shendrik R, Titov E, Sukhov B. Synthesis and comparative assessment of antiradical activity, toxicity, and biodistribution of κ-carrageenan-capped selenium nanoparticles of different size: in vivo and in vitro study. IET Nanobiotechnology. 2020;14(6):519–26.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Guo L, Xiao J, Liu H, Liu H. Selenium nanoparticles alleviate hyperlipidemia and vascular injury in ApoE-deficient mice by regulating cholesterol metabolism and reducing oxidative stress. Metallomics Roy Soc Chem. 2020;12(2):204–17.

    Article  CAS  Google Scholar 

  44. Xiao J, Cao H, Guo S, Xiao S, Li N, Li M, et al. Long-term administration of low-dose selenium nanoparticles with different sizes aggravated atherosclerotic lesions and exhibited toxicity in apolipoprotein E-deficient mice. Chem Biol Interact. 2021;347:109601.

    Article  CAS  PubMed  Google Scholar 

  45. Bai K, Hong B, He J, Hong Z, Tan R. Preparation and antioxidant properties of selenium nanoparticles-loaded chitosan microspheres. Int J Nanomedicine. 2017;12:4527–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang Z, Du Y, Liu T, Wong KH, Chen T. Systematic acute and subchronic toxicity evaluation of polysaccharide-protein complex-functionalized selenium nanoparticles with anticancer potency. Biomater Sci. 2019;7(12):5112–23.

    Article  CAS  PubMed  Google Scholar 

  47. Bhattacharjee A, Basu A, Bhattacharya S. Selenium nanoparticles are less toxic than inorganic and organic selenium to mice in vivo. Nucl. 2019;62(3):259–68.

    Article  Google Scholar 

  48. Benko I, Nagy G, Tanczos B, Ungvari E, Sztrik A, Eszenyi P, et al. Subacute toxicity of nano-selenium compared to other selenium species in mice. Environ Toxicol Chem. 2012;31(12):2812–20.

    Article  CAS  PubMed  Google Scholar 

  49. Kondaparthi P, Deore M, Naqvi S, Flora SJS. Dose-dependent hepatic toxicity and oxidative stress on exposure to nano and bulk selenium in mice. Environ Sci Pollut Res. 2021;28(38):53034–44.

    Article  CAS  Google Scholar 

  50. Bai K, Hong B, Hong Z, Sun J, Wang C. Selenium nanoparticles-loaded chitosan/citrate complex and its protection against oxidative stress in d-galactose-induced aging mice. J Nanobiotechnology BioMed Central. 2017;15:92

  51. Zhang J, Wang H, Yan X, Zhang L. Comparison of short-term toxicity between Nano-se and selenite in mice. Life Sci. 2005;76(10):1099–109.

    Article  CAS  PubMed  Google Scholar 

  52. Wang HL, Zhang JS, Yu HQ. Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice. Free Radic Biol Med. 2007;42(10):1524–33.

    Article  CAS  PubMed  Google Scholar 

  53. Shakibaie M, Shahverdi AR, Faramarzi MA, Hassanzadeh GR, Rahimi HR, Sabzevari O. Acute and subacute toxicity of novel biogenic selenium nanoparticles in mice. Pharm Biol. 2013;51(1):58–63.

    Article  CAS  PubMed  Google Scholar 

  54. Wang H, He Y, Liu L, Tao W, Wang G, Sun W, et al. Prooxidation and cytotoxicity of selenium nanoparticles at nonlethal level in Sprague-Dawley rats and Buffalo rat liver cells. Oxid Med Cell Longev. 2020;2020:7680276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chandramohan S, Naveenkumar S, Kaviyarasu K, Lavakumar V, Sowmya C, Santhanakumar M, et al. Bio-distribution of selenium nanoparticles (SeNPs) to the Wistar rats and its breastfed offspring. J Drug Deliv Sci Technol. 2021;61:102299.

    Article  CAS  Google Scholar 

  56. Urbankova L, Horky P, Skladanka J, Pribilova M, Smolikova V, Nevrkla P, et al. Antioxidant status of rats’ blood and liver affected by sodium selenite and selenium nanoparticles. PeerJ. 2018;6:e4862.

  57. Liu L, He Y, Xiao Z, Tao W, Zhu J, Wang B, et al. Effects of selenium nanoparticles on reproductive performance of male Sprague-Dawley rats at Supranutritional and nonlethal levels. Biol Trace Elem Res. 2017;180(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  58. Urbankova L, Skalickova S, Pribilova M, Ridoskova A, Pelcova P, Skladanka J, et al. Effects of sub-lethal doses of selenium nanoparticles on the health status of rats. Toxics. 2021;9(2):28.

  59. Mercan Yücel U, Başbuğan Y, Uyar A, Kömüroğlu AU, Keleş ÖF. Use of an antiarrhythmic drug against acute selenium toxicity. J Trace Elem Med Biol. 2020;59:126471.

    Article  CAS  PubMed  Google Scholar 

  60. Jia X, Li N, Chen J. A subchronic toxicity study of elemental Nano-se in Sprague-Dawley rats. Life Sci. 2005;76(17):1989–2003.

    Article  CAS  PubMed  Google Scholar 

  61. Zhang JS, Gao XY, Zhang LD, Bao YP. Biological effects of a nano red elemental selenium. Biofactors. 2001;15(1):27–38.

    Article  PubMed  Google Scholar 

  62. Bami MK, Afsharmanesh M, Espahbodi M, Angkanaporn K. Dietary supplementation with biosynthesised nano-selenium affects growth, carcass characteristics, meat quality and blood parameters of broiler chickens. Anim Prod Sci. 2021;62(3):254–62.

    Article  CAS  Google Scholar 

  63. Hu CH, Li YL, Xiong L. Comparative effects of nano elemental selenium and sodium selenite on selenium retention in broiler chickens. Anim Feed Sci Technol. 2012;177(3-4):204–10.

    Article  CAS  Google Scholar 

  64. Bakhshalinejad R, Hassanabadi A, Swick RA. Dietary sources and levels of selenium supplements affect growth performance, carcass yield, meat quality and tissue selenium deposition in broilers. Anim Nutr. 2019;5(3):256–63.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Gangadoo S, Dinev I, Willson NL, Moore RJ, Chapman J, Stanley D. Nanoparticles of selenium as high bioavailable and non-toxic supplement alternatives for broiler chickens. Environ Sci Pollut Res. 2020;27:16159–66.

  66. Lee J, Hosseindoust A, Kim M, Kim K, Choi Y, Lee S, et al. Biological evaluation of hot-melt extruded Nano-selenium and the role of selenium on the expression profiles of selenium-dependent antioxidant enzymes in chickens. Biol Trace Elem Res. 2020;194(2):536–44.

    Article  CAS  PubMed  Google Scholar 

  67. Li Y, He J, Shen X. Effects of Nano-selenium poisoning on immune function in the Wumeng semi-fine wool sheep. Biol Trace Elem Res. 2021;199(8):2919–24.

    Article  CAS  PubMed  Google Scholar 

  68. Lee J, Hosseindoust A, Kim M, Kim K, Choi Y, Lee S, et al. Supplemental hot melt extruded nano-selenium increases expression profiles of antioxidant enzymes in the livers and spleens of weanling pigs. Anim Feed Sci Technol. 2020;262:114381.

    Article  CAS  Google Scholar 

  69. Zheng Y, Dai W, Hu X, Hong Z. Effects of dietary glycine selenium nanoparticles on loin quality, tissue selenium retention, and serum antioxidation in finishing pigs. Anim Feed Sci Technol. 2020;260:114345.

    Article  CAS  Google Scholar 

  70. Xun W, Shi L, Yue W, Zhang C, Ren Y, Liu Q. Effect of high-dose nano-selenium and selenium–yeast on feed digestibility, rumen fermentation, and purine derivatives in sheep. Biol Trace Elem Res. 2012;150(1-3):130–6.

    Article  CAS  PubMed  Google Scholar 

  71. Han L, Pang K, Fu T, Phillips CJC, Gao T. Nano-selenium supplementation increases selenoprotein (Sel) gene expression profiles and milk selenium concentration in lactating dairy cows. Biol Trace Elem Res. 2021;199(1):113–9.

    Article  CAS  PubMed  Google Scholar 

  72. Bai K, Hong B, Tan R, He J, Hong Z. Selenium nanoparticles-embedded chitosan microspheres and their effects upon alcohol-induced gastric mucosal injury in rats: Rapid preparation, oral delivery, and gastroprotective potential of selenium nanoparticles. Int J Nanomedicine. 2020;15:1187.

    Article  CAS  Google Scholar 

  73. Karami M, Asri-Rezaei S, Dormanesh B, Nazarizadeh A. Comparative study of radioprotective effects of selenium nanoparticles and sodium selenite in irradiation-induced nephropathy of mice model. Int J Radiat Biol. 2018;94:17–27.

    Article  CAS  Google Scholar 

  74. Wang H, Wei W, Zhang S, Shen Y, Yue L, Wang N, et al. Melatonin-selenium nanoparticles inhibit oxidative stress and protect against hepatic injury induced by Bacillus Calmette–Guérin/lipopolysaccharide in mice. J Pineal Res. 2005;39:156–63.

    Article  CAS  Google Scholar 

  75. Dahdouh F, Bendjeffal H, Nouacer Z, Moumene W, Zeminour ME-H, Naous M, et al. Selenium nanoparticles attenuate gentamycin-induced nephrotoxicity and Hematotoxicity in female Swiss albino mice. Bionanoscience. 2019;9(2):356–64.

    Article  Google Scholar 

  76. Alkhudhayri AA, Dkhil MA, Al-Quraishy S. Nanoselenium prevents eimeriosis-induced inflammation and regulates mucin gene expression in mice jejunum. Int J Nanomedicine. 2018;13:1993.

    Article  CAS  Google Scholar 

  77. Sohrabi A, Tehrani AA, Asri-Rezaei S, Zeinali A, Norouzi M. Histopathological assessment of protective effects of selenium nanoparticles on rat hepatocytes exposed to Gamma radiation. Vet Res Forum. 2020;11(4):347–53.

  78. Hassanin KMA, Abd El-Kawi SH, Hashem KS. The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid. Int J Nanomedicine. 2013;8:1713.

    PubMed  PubMed Central  Google Scholar 

  79. Hozyen HF, Khalil HMA, Ghandour RA, Al-Mokaddem AK, Amer MS, Azouz RA. Nano selenium protects against deltamethrin-induced reproductive toxicity in male rats. Toxicol Appl Pharmacol. 2020;408:115274.

    Article  CAS  Google Scholar 

  80. Al-Brakati A, Alsharif KF, Alzahrani KJ, Kabrah S, Al-Amer O, Oyouni AA, et al. Using green biosynthesized lycopene-coated selenium nanoparticles to rescue renal damage in glycerol-induced acute kidney injury in rats. Int J Nanomedicine. 2021;16:4335.

  81. Al-Kahtani M, Morsy K. Ameliorative effect of selenium nanoparticles against aluminum chloride-induced hepatorenal toxicity in rats. Environ Sci Pollut Res. 2019;26(31):32189–97.

    Article  CAS  Google Scholar 

  82. Fakhr Almobasheri N, Shahanipour K, Monajemi R. The protective effect of selenium nanoparticles and selenium against paracetamol. Nanomedicine J. 2018;5:52–6.

    Google Scholar 

  83. Nasirpour M, Sadeghi AA, Chamani M. Effects of nano-selenium on the liver antioxidant enzyme activity and immunoglobolins in male rats exposed to oxidative stress. J Livest Sci. 2017;8:81–7.

    Google Scholar 

  84. Rezaei-Kelishadi M, Ghasemi A, Abdolyosefi NN, Zamani-Doabi S, Ramezani M, Changizi-Ashtiyani S, et al. Effects of selenium nanoparticles on kidney and liver functional disorders in streptozotocin-induced diabetic rats. Physiol Pharmacol. 2017;21:155–62.

    Google Scholar 

  85. Khalaf AA, Ahmed WMS, Moselhy WA, Abdel-Halim BR, Ibrahim MA. Protective effects of selenium and nano-selenium on bisphenol-induced reproductive toxicity in male rats. Hum Exp Toxicol. 2019;38:398–408.

  86. Vekariya KK, Kaur J, Tikoo K. Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats. Toxicol Appl Pharmacol. 2013;268(2):212–20.

    Article  CAS  PubMed  Google Scholar 

  87. Yue D, Zeng C, Okyere SK, Chen Z, Hu Y. Glycine nano-selenium prevents brain oxidative stress and neurobehavioral abnormalities caused by MPTP in rats. J Trace Elem Med Biol. 2021;64:126680.

    Article  CAS  Google Scholar 

  88. El-Megharbel SM, Al-Salmi FA, Al-Harthi S, Alsolami K, Hamza RZ. Chitosan/Selenium nanoparticles attenuate diclofenac sodium-induced testicular toxicity in male rats. Crystals. 2021;11:1477.

  89. AlBasher G, Alfarraj S, Alarifi S, Alkhtani S, Almeer R, Alsultan N, et al. Nephroprotective role of selenium nanoparticles against glycerol-induced acute kidney injury in rats. Biol Trace Elem Res. 2020;194(2):444–54.

    Article  CAS  PubMed  Google Scholar 

  90. Khiralla G, Elhariry H, Selim SM. Chitosan-stabilized selenium nanoparticles attenuate acrylamide-induced brain injury in rats. J Food Biochem. 2020;44:e13413.

    Article  CAS  Google Scholar 

  91. Dkhil MA, Zrieq R, Al-Quraishy S, Abdel Moneim AE. Selenium nanoparticles attenuate oxidative stress and testicular damage in streptozotocin-induced diabetic rats. Molecules. 2016;21:1517.

    Article  Google Scholar 

  92. Alhazza IM, Ebaid H, Omar MS, Hassan I, Habila MA, Al-Tamimi J, et al. Supplementation with selenium nanoparticles alleviates diabetic nephropathy during pregnancy in the diabetic female rats. Environ Sci Pollut Res. 2022;29(4):5517–25.

    Article  CAS  Google Scholar 

  93. Lesnichaya M, Karpova E, Sukhov B. Effect of high dose of selenium nanoparticles on antioxidant system and biochemical profile of rats in correction of carbon tetrachloride-induced toxic damage of liver. Colloids Surf B Biointerfaces. 2021;197:111381.

    Article  CAS  Google Scholar 

  94. Ebaid H, Al-Tamimi J, Hassan I, Habila MA, Rady AM, Alhazza IM, et al. Effect of selenium nanoparticles on carbon tetrachloride-induced hepatotoxicity in the swiss albino rats. Appl Sci. 2021;11(7):3044.

  95. Ali HFH, El-Sayed NM, khodeer DM, Ahmed AAM, Hanna PA, Moustafa YMA. Nano selenium ameliorates oxidative stress and inflammatory response associated with cypermethrin-induced neurotoxicity in rats. Ecotoxicol Environ Saf. 2020;195:110479.

    Article  CAS  PubMed  Google Scholar 

  96. Hassan I, Ebaid H, Al-Tamimi J, Habila MA, Alhazza IM, Rady AM. Selenium nanoparticles mitigate diabetic nephropathy and pancreatopathy in rat offspring via inhibition of oxidative stress. J King Saud Univ - Sci. 2021;33(1):101265.

    Article  Google Scholar 

  97. Sadek KM, Lebda MA, Abouzed TK, Nasr SM, Shoukry M. Neuro- and nephrotoxicity of subchronic cadmium chloride exposure and the potential chemoprotective effects of selenium nanoparticles. Metab Brain Dis. 2017;32(5):1659–73.

    Article  CAS  PubMed  Google Scholar 

  98. Ebokaiwe AP, Okori S, Nwankwo JO, Ejike CECC, Osawe SO. Selenium nanoparticles and metformin ameliorate streptozotocin-instigated brain oxidative-inflammatory stress and neurobehavioral alterations in rats. Naunyn Schmiedeberg's Arch Pharmacol. 2021;394(4):591–602.

    Article  CAS  Google Scholar 

  99. Abu-Zeid EH, Abdel Fattah DM, Arisha AH, Ismail TA, Alsadek DM, Metwally MMM, et al. Protective prospects of eco-friendly synthesized selenium nanoparticles using Moringa oleifera or Moringa oleifera leaf extract against melamine induced nephrotoxicity in male rats. Ecotoxicol Environ Saf. 2021;221:112424.

    Article  CAS  PubMed  Google Scholar 

  100. Sheiha AM, Abdelnour SA, Abd El-Hack ME, Khafaga AF, Metwally KA, Ajarem JS, et al. Effects of dietary biological or chemical-synthesized nano-selenium supplementation on growing rabbits exposed to thermal stress. Animals. 2020;10(3):430.

  101. Hassan RA, Soliman ES, Hamad RT, El-Borady OM, Ali AA, Helal MS. Selenium and nano-selenium ameliorations in two breeds of broiler chickens exposed to heat stress. South African J Anim Sci. 2020;50(2):215–32.

    Article  CAS  Google Scholar 

  102. Shirsat S, Kadam A, Mane RS, Jadhav VV, Zate MK, Naushad M, et al. Protective role of biogenic selenium nanoparticles in immunological and oxidative stress generated by enrofloxacin in broiler chicken. Dalton Trans. 2016;45:8845–53.

    Article  CAS  Google Scholar 

  103. Boostani A, Sadeghi AA, Mousavi SN, Chamani M, Kashan N. Effects of organic, inorganic, and nano-se on growth performance, antioxidant capacity, cellular and humoral immune responses in broiler chickens exposed to oxidative stress. Livest Sci. 2015;178:330–6.

    Article  Google Scholar 

  104. Zhang T, Zhao Y, Li L, Zhou D. Antagonistic effects of nano-selenium on broilers hepatic injury induced by Cr(VI) poisoning in AMPK pathway. Environ Sci Pollut Res. 2020;27(33):41585–95.

    Article  CAS  Google Scholar 

  105. Li Y, Fan M, Qiu Q, Wang Y, Shen X, Zhao K. Nano-selenium and Macleaya cordata extracts improved immune function and reduced oxidative damage of sows and IUGR piglets after heat stress of sows in late gestation. Biol Trace Elem Res. 2022.

  106. Liu C, Li Y, Li H, Wang Y, Zhao K. Nano-selenium and Macleaya cordata extracts improved immune functions of intrauterine growth retardation piglets under maternal oxidation stress. Biol Trace Elem Res. 2021.

Download references


Not applicable.


Work has been funded by TJ04000198: Influence of selenium and vitamin E in wagyu hybrids on reproductive properties and meat performance.

Author information

Authors and Affiliations



IB and PH designed the review. IB, SA and LU production of tables and Figs. IB, SA, LU and PH analysis of current knowledge, IB and PH wrote the manuscript, SS and PH edited the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Pavel Horky.

Ethics declarations

Ethics approval and consent to participate

Experiments on animals were not provided.

Consent for publication

We consent to publication of the manuscript.

Competing interests

We declare we do not have competing interests.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bano, I., Skalickova, S., Arbab, S. et al. Toxicological effects of nanoselenium in animals. J Animal Sci Biotechnol 13, 72 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: