Protective effect of selenomethionine on rabbit testicular injury induced by Aflatoxin B1.

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.

The application of organic selenium (SeMet) improve the photosynthetic characteristics, yield and quality of hybrid rice.

Rice is an important food in the world, and selenium (Se) is a necessary trace element for the human. So the effects of selenomethionine (SeMet) on photosynthetic capacity, yield and quality of rice at different stages were studied. The results show that SeMet can increase the Ppotosynthetic capacity of rice leaves during each growth stage, the effect of 5 mg/L SeMet treatment was the most significant. At the mature stage of rice, SeMet significantly increased rice yield and total plant biomass, 7.5and 5 mg/L SeMet treatments had the most significant effects, respectively. In addition, SeMet significantly improved the content of Se and processing quality of rice, decreased chalkiness, inhibited amylose synthesis, and optimized flavor. The above indices showed the best results after treatment with 5 mg/L SeMet. It is hoped that this study will provide a theoretical basis for the application of organic selenium in rice production.

Effects of various selenium-enriched yeasts, selenomethionine, and nanoselenium on production performance, quality, and antioxidant capacity in laying hens.

This study aimed to compare the effects of various selenium (Se) sources (2 mg/kg) on the performance, quality, and antioxidant capacity of laying hens as well as the Se content in their eggs and blood. We selected 720 34-wk-old Lohmann pink-shell laying hens were randomly assigned into 6 groups and fed a basal diet (control) or a basal diet supplemented with various Se sources (Se-enriched yeast, SY-A, SY-C, SY-N; selenomethionine SM, nano-Se SN) for 16 wk. There were 10 replicates of 120 hens per group. Dietary Se supplementation increased the egg production rate of all laying hens. Egg and serum Se deposition was highest in the SM group. Yolk color scores of SY-A and SY-N groups were significantly lower than those of other groups (P < 0.01). The protein height and Haugh unit were significantly lower in the SN group than in the other groups (P < 0.05). The yolk height was significantly higher in the SN and SY-N groups than in the SY-A group (P < 0.05). Dietary supplementation of selenium can improve the antioxidant capacity of laying hens. The SOD content of SM group was significantly lower than that of SY-A and SN group (P < 0.05). The malondialdehyde (MDA) content was significantly higher in the SM group than in the SY-A group (P < 0.05). The present work empirically demonstrated that the production performance of laying hens supplemented with 2 mg/kg Se was superior to that of the hens receiving only a basal diet. The SY-C group exhibited the best production performance, the SY-A group had the highest antioxidant capacity, and the SM group produced eggs with the highest level of Se enrichment.

By regulating the IP3R/GRP75/VDAC1 complex to restore mitochondrial dynamic balance, selenomethionine reduces lipopolysaccharide-induced neuronal apoptosis.

Selenium (Se), as one of the essential trace elements, plays an anti-inflammatory, antioxidation, and immune-enhancing effect in the body. In addition, Se can also improve nervous system damage induced by various factors. Earlier studies have described the important role of mitochondrial dynamic imbalance in lipopolysaccharide (LPS)-induced nerve injury. The inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (GRP75)/voltage-dependent anion channel 1 (VDAC1) complex is considered to be the key to regulating mitochondrial dynamics. However, it is not clear whether Selenomethionine (SeMet) has any influence on the IP3R/GRP75/VDAC1 complex. Therefore, the aim of this investigation was to determine whether SeMet can alleviate LPS-induced brain damage and to elucidate the function of the IP3R/GRP75/VDAC1 complex in it. We established SeMet and/or LPS exposure models in vivo and in vitro using laying hens and primary chicken nerve cells. We noticed that SeMet reversed endoplasmic reticulum stress (ERS) and the imbalance in mitochondrial dynamics and significantly prevented the occurrence of neuronal apoptosis. We made this finding by morphological observation of the brain tissue of laying hens and the detection of related genes such as ERS, the IP3R/GRP75/VDAC1 complex, calcium signal (Ca2+), mitochondrial dynamics, and apoptosis. Other than that, we also discovered that the IP3R/GRP75/VDAC1 complex was crucial in controlling Ca2+ transport between the endoplasmic reticulum and the mitochondrion when SeMet functions as a neuroprotective agent. In summary, our results revealed the specific mechanism by which SeMet alleviated LPS-induced neuronal apoptosis for the first time. As a consequence, SeMet has great potential in the treatment and prevention of neurological illnesses (like neurodegenerative diseases).

Dietary selenomethionine reduced oxidative stress by resisting METTL3-mediated m6A methylation level of Nrf2 to ameliorate LPS-induced liver necroptosis in laying hens.

Selenomethionine (SeMet) as the main form of daily dietary selenium, occupies essential roles in providing antioxidant and anti-inflammatory properties, which alleviates inflammatory liver damage. N6-methyladenosine (m6A) is one of the most prevalent and abundant internal transcriptional modifications that regulate gene expression. To investigate the protective mechanism of SeMet on liver injury and the regulatory effect of m6A methylation modification, we established the model by supplementing dietary SeMet, and LPS as stimulus in laying hens. LMH cells were intervened with SeMet (0.075 µM) and/or LPS (60 µg/mL). Subsequently, histopathology and ultrastructure of liver were observed. Western Blot, qRT-PCR, colorimetry, MeRIP-qPCR, fluorescent probe staining and AO/EB were used to detect total m6A methylation level, m6A methylation level of Nrf2, ROS, inflammatory and necroptosis factors. Studies showed that SeMet suppressed LPS-induced upregulation of total m6A methylation levels and METTL3 expression. Interestingly, SeMet reduced the m6A methylation level of Nrf2, activated antioxidant pathways and alleviated oxidative stress. LMH cells were transfected with 50 µm siMETTL3. SeMet/SiMETTL3 reversed the LPS-induced reduction in Nrf2 mRNA stability, slowed down its degradation rate. Moreover, LPS induced oxidative stress, led to necroptosis and activated NF-κB to promote the expression of inflammatory factors. SeMet/SiMETTL3 alleviated LPS-induced necroptosis and inflammation. Altogether, SeMet enhanced antioxidant and anti-inflammatory capacity by reducing METTL3-mediated m6A methylation levels of Nrf2, ultimately alleviating liver damage. Our findings provided new insights and therapeutic target for the practical application of dietary SeMet in the treatment and prevention of liver inflammation, and supplied a reference for comparative medicine.

Selenomethionine modulates the JAK2 / STAT3 / A20 pathway through oxidative stress to alleviate LPS-induced pyroptosis and inflammation in chicken hearts.

Selenium (Se) is involved in many physiopathologic processes in humans and animals and is strongly associated with the development of heart disease. Lipopolysaccharides (LPS) are cell wall components of gram-negative bacteria that are present in large quantities during environmental pollution. To investigate the mechanism of LPS-induced cardiac injury and the efficacy of the therapeutic effect of SeMet on LPS, a chicken model supplemented with selenomethionine (SeMet) and/or LPS treatment, as well as a primary chicken embryo cardiomyocyte model with the combined effect of SeMet / JAK2 inhibitor (INCB018424) and/or LPS were established in this experiment. CCK8 kit, Trypan blue staining, DCFH-DA staining, oxidative stress kits, immunofluorescence staining, LDH kit, real-time fluorescence quantitative PCR, and western blot were used. The results proved that LPS exposure led to ROS explosion, hindered the antioxidant system, promoted the expression of the JAK2 pathway, and increased the expression of genes involved in the pyroptosis pathway, inflammatory factors, and heat shock proteins (HSPs). Upon co-treatment with SeMet and LPS, SeMet reduced LPS-induced pyroptosis and inflammation and restored the expression of HSPs by inhibiting the ROS burst and modulating the antioxidant capacity. Co-treatment with INCB018424 and LPS resulted in inhibited of the JAK2 pathway, attenuating pyroptosis, inflammation, and high expression of HSPs. Thus, LPS induced pyroptosis, inflammation, and changes in HSPs activity by activating of the JAK2 / STAT3 / A20 signaling axis in chicken hearts. Moreover, SeMet has a positive effect on LPS-induced injury. This work further provides a theoretical basis for treating cardiac injury by SeMet.

SeMet alleviates LPS-induced eggshell gland necroptosis mediated inflammation by regulating the Keap1/Nrf2/HO-1 pathway.

Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRT‒PCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens.

SeMet alleviates AFB1-induced oxidative stress and apoptosis in rabbit kidney by regulating Nrf2//Keap1/NQO1 and PI3K/AKT signaling pathways.

The purpose of this study was to explore the protective effect of SeMet on renal injury induced by AFB1 in rabbits and its molecular mechanism. Forty rabbits of 35 days old were randomly divided into control group, AFB1 group (0.3 mg AFB1/kg b.w), 0.2 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.2 mg SeMet/kg feed) and 0.4 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.4 mg SeMet/kg feed). The SeMet treatment group was fed different doses of SeMet diets every day for 21 days. On the 17-21 day, the AFB1 treatment group, the 0.2 mg/kg Se + AFB1 group and the 0.4 mg/kg Se + AFB1 group were administered 0.3 mg AFB1 /kg b.w by gavage (dissolved in 0.5 ml olive oil) respectively. The results showed that AFB1 poisoning resulted in the changes of renal structure, the increase of renal coefficient and serum biochemical indexes, the ascent of ROS and MDA levels, the descent of antioxidant enzyme activity, and the significant down-regulation of Nrf2, HO-1 and NQO1. Besides, AFB1 poisoning increased the number of renal apoptotic cells, rised the levels of PTEN, Bax, Caspase-3 and Caspase-9, and decreased the levels of PI3K, AKT, p-AKT and Bcl-2. In summary, SeMet was added to alleviate the oxidative stress injury and apoptosis of kidney induced by AFB1, and the effect of 0.2 mg/kg Se + AFB1 is better than 0.4 mg/kg Se + AFB1.

Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice.

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

Selenomethionine Inhibits NF-κB-mediated Inflammatory Responses of Bovine Mammary Epithelial Cells Caused by Klebsiella pneumoniae by Increasing Autophagic Flux.

Klebsiella pneumoniae (K. pneumoniae) is one of the major pathogens causing bovine clinical mastitis. Autophagy maintains cellular homeostasis and resists excessive inflammation in eukaryotic organisms. Selenomethionine (Se-Met) is commonly used as a source of selenium supplementation for dairy cows. This study aimed to investigate the effects of Se-Met on inflammatory responses mediated by nuclear factor-kappa B (NF-κB) through autophagy. We infected bovine mammary epithelial cell line (MAC-T) with K. pneumoniae and examined the expression of autophagy-related proteins and changes in autophagic vesicles, LC3 puncta, and autophagic flux at various intervals. The results showed that K. pneumoniae activated the early-stage autophagy of MAC-T cells. The levels of LC3-II, Beclin1, and ATG5, as well as the number of LC3 puncta and autophagic vesicles, increased after 2 h post-treatment. However, the late-stage autophagic flux was blocked. Furthermore, the effect of autophagy on NF-κB-mediated inflammation was investigated with different autophagy levels. The findings showed that enhanced autophagy inhibited the K. pneumoniae-induced inflammatory responses of MAC-T cells. The opposite results were found with the inhibition of autophagy. Finally, we examined the effect of Se-Met on NF-κB-mediated inflammation based on autophagy. The results indicated that Se-Met alleviated K. pneumoniae-induced autophagic flux blockage, inhibited NF-κB-mediated inflammation, and decreased the adhesion of K. pneumoniae to MAC-T cells. The inhibitory effect of Se-Met on NF-κB-mediated inflammation could be partially blocked by the autophagy inhibitor chloroquine (CQ). Overall, Se-Met attenuated K. pneumoniae-induced NF-κB-mediated inflammatory responses by enhancing autophagic flux.

Selenomethionine alleviates environmental heat stress induced hepatic lipid accumulation and glycogen infiltration of broilers via maintaining mitochondrial and endoplasmic reticulum homeostasis.

With the increasing of global mean surface air temperature, heat stress (HS) induced by extreme high temperature has become a key factor restricting the poultry industry. Liver is the main metabolic organ of broilers, HS induces liver damage and metabolic disorders, which impairs the health of broilers and affects food safety. As an essential trace element for animals, selenium (Se) involves in the formation of antioxidant system, and its biological functions are generally mediated by selenoproteins. However, the mechanism of Se against HS induced liver damage and metabolic disorders in broilers is inadequate. Therefore, we developed the chronic heat stress (CHS) broiler model and investigated the potential protection mechanism of organic Se (selenomethionine, SeMet) on CHS induced liver damage and metabolic disorders. In present study, CHS caused liver oxidative damage, and induced hepatic lipid accumulation and glycogen infiltration of broilers, which are accompanied by mitochondrial dysfunction, abnormal mitochondrial tricarboxylic acid (TCA) cycle and endoplasmic reticulum (ER) stress. Dietary SeMet supplementation increased the hepatic Se concentration and exhibited protective effects via promoting the expression of selenotranscriptome and several key selenoproteins (GPX4, TXNRD2, SELENOK, SELENOM, SELENOS, SELENOT, GPX1, DIO1, SELENOH, SELENOU and SELENOW). These key selenoproteins synergistically improved the antioxidant capacity, and mitigated the mitochondrial dysfunction, abnormal mitochondrial TCA cycle and ER stress, thus recovered the hepatic triglyceride and glycogen concentration. What's more, SeMet supplementation suppressed lipid and glycogen biosynthesis and promoted lipid and glycogen breakdown in liver of broilers exposed to CHS though regulating the AMPK signals. Overall, our present study reveals a potential mechanism that Se alleviates environment HS induced liver damage and glycogen and lipid metabolism disorders in broilers, which provides a preventive and/or treatment measure for environment HS-dependent hepatic metabolic disorders in poultry industry.

Transcriptome-based exploration of potential molecular targets and mechanisms of selenomethionine in alleviating renal ischemia-reperfusion injury.

Renal ischemia-reperfusion injuries (IRIs) are one of the leading causes of acute kidney injuries (AKIs). Selenium, as an essential trace element, is able to antioxidant stress and reduces inflammatory responses. The regulation mechanism of selenomethionine, one of the major forms of selenium intake by humans, is not yet clear in renal IRIs. Therefore, we aimed to explore the key targets and related mechanisms of selenomethionine regulation in renal IRIs and provide new ideas for the treatment of selenomethionine with renal IRIs. We used transcriptome sequencing data from public databases as well as animal experiments to explore the key target genes and related mechanisms regulated by selenomethionine in renal IRI. We found that selenomethionine can effectively alleviate renal IRI by a mechanism that may be achieved by inhibiting the MAPK signaling pathway. Meanwhile, we also found that the key target of selenomethionine regulation in renal IRI might be selenoprotein GPX3 based on the PPI protein interaction network and machine learning. Through a comprehensive analysis of bioinformatic techniques and animal experiments, we found that Gpx3 might serve as a key gene for the regulation of selenomethionine in renal IRIs. Selenomethionine may exert a protective effect against renal IRI by up-regulating GPX3, inhibiting the MAPK signaling pathway, increased production of antioxidants, decreasing inflammation levels, mitigation of apoptosis in renal tubular epithelial cells, this reduces renal histopathological damage and protects renal function. Providing a theoretical basis for the mechanism of selenomethionine actions in renal IRIs.

Selenomethionine Antagonized microRNAs Involved in Apoptosis of Rat Articular Cartilage Induced by T-2 Toxin.

T-2 toxin and selenium deficiency are considered important etiologies of Kashin-Beck disease (KBD), although the exact mechanism is still unclear. To identify differentially expressed microRNAs (DE-miRNAs) in the articular cartilage of rats exposed to T-2 toxin and selenomethionine (SeMet) supplementation, thirty-six 4-week-old Sprague Dawley rats were divided into a control group (gavaged with 4% anhydrous ethanol), a T-2 group (gavaged with 100 ng/g·bw/day T-2 toxin), and a T-2 + SeMet group (gavaged with 100 ng/g·bw/day T-2 toxin and 0.5 mg/kg·bw/day SeMet), respectively. Toluidine blue staining was performed to detect the pathological changes of articular cartilage. Three rats per group were randomly selected for high-throughput sequencing of articular cartilage. Target genes of DE-miRNAs were predicted using miRanda and RNAhybrid databases, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were enriched. The network map of miRNA-target genes was constructed using Cytoscape software. The expression profiles of miRNAs associated with KBD were obtained from the Gene Expression Omnibus database. Additionally, the DE-miRNAs were selected for real-time quantitative PCR (RT-qPCR) verification. Toluidine blue staining demonstrated that T-2 toxin damaged articular cartilage and SeMet effectively alleviated articular cartilage lesions. A total of 50 DE-miRNAs (28 upregulated and 22 downregulated) in the T-2 group vs. the control group, 18 DE-miRNAs (6 upregulated and 12 downregulated) in the T-2 + SeMet group vs. the control group, and 25 DE-miRNAs (5 upregulated and 20 downregulated) in the T-2 + SeMet group vs. the T-2 group were identified. Enrichment analysis showed the target genes of DE-miRNAs were associated with apoptosis, and in the MAPK and TGF-ß signaling pathways in the T-2 group vs. the control group. However, the pathway of apoptosis was not significant in the T-2 + SeMet group vs. the control group. These results indicated that T-2 toxin induced apoptosis, whereas SeMet supplementation antagonized apoptosis. Apoptosis and autophagy occurred simultaneously in the T-2 + SeMet group vs. T-2 group, and autophagy may inhibit apoptosis to protect cartilage. Compared with the GSE186593 dataset, the evidence of miR-133a-3p involved in apoptosis was more abundant. The results of RT-qPCR validation were consistent with RNA sequencing results. Our findings suggested that apoptosis was involved in articular cartilage lesions induced by T-2 toxin, whereas SeMet supplementation antagonized apoptosis, and that miR-133a-3p most probably played a central role in the apoptosis process.

Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

Chronic dietary exposure to arsenic at environmentally relevant concentrations impairs cognitive performance in adult zebrafish (Danio rerio) via oxidative stress and dopaminergic dysfunction.

The current study was designed to evaluate the effects of chronic dietary arsenic exposure on the cognitive performance of adult zebrafish and uncover probable pathways by which arsenic mediates such neurotoxic effects. Adult zebrafish were treated with 3 different dietary arsenic concentrations (30, 60, and 100 µg/g dry weight (dw), as arsenite) in addition to control for 60 days. A latent learning paradigm, which employs a complex maze, was used to assess the cognitive performance of fish. Our results demonstrated that dietary treatment with arsenic, especially at medium (60 µg/g dw) and high (100 µg/g dw) exposure dose levels, significantly impaired the performance of fish in various latent learning tasks evaluated in the present study. Concomitant with cognitive dysfunction, chronic dietary exposure to arsenic was also found to increase arsenic accumulation and dopamine levels, and induce oxidative stress (reduced thiol redox, increased lipid peroxidation and expression of antioxidant enzyme genes) in the brain of zebrafish in a dose-dependent manner. Dopaminergic system in the brain is known to play a critical role in regulating cognitive behaviours in fish, and our observations suggested that chronic dietary treatment with medium and high arsenic doses leads to significant alterations in the expression of genes involved in dopamine signaling (dopamine receptors), synthesis (thyroxine hydroxylase) and metabolism (monoamine oxidase) in the zebrafish brain. Moreover, we also recorded significant downregulation of genes such as the brain-derived neurotrophic factor (BDNF) and ectonucleotidases (entpd2_mg, entpd2_mq, and 5'-nucleotidase), which are critical for learning and memory functions, in the zebrafish brain following chronic dietary exposure to arsenic. Overall, the present study suggests that chronic environmentally relevant dietary exposure to arsenic can impair the cognitive performance in zebrafish, essentially by inducing oxidative stress and disrupting the dopaminergic neurotransmission in the brain.

Evaluation of Selenomethionine Entrapped in Nanoparticles for Oral Supplementation Using In Vitro, Ex Vivo and In Vivo Models.

Selenium methionine (SeMet) is an essential micronutrient required for normal body function and is associated with additional health benefits. However, oral administration of SeMet can be challenging due to its purported narrow therapeutic index, low oral bioavailability, and high susceptibility to oxidation. To address these issues, SeMet was entrapped in zein-coated nanoparticles made from chitosan using an ionic gelation formulation. The high stability of both the SeMet and selenomethionine nanoparticles (SeMet-NPs) was established using cultured human intestinal and liver epithelial cells, rat liver homogenates, and rat intestinal homogenates and lumen washes. Minimal cytotoxicity to Caco-2 and HepG2 cells was observed for SeMet and SeMet-NPs. Antioxidant properties of SeMet were revealed using a Reactive Oxygen Species (ROS) assay, based on the observation of a concentration-dependent reduction in the build-up of peroxides, hydroxides and hydroxyl radicals in Caco-2 cells exposed to SeMet (6.25-100 µM). The basal apparent permeability coefficient (Papp) of SeMet across isolated rat jejunal mucosae mounted in Ussing chambers was low, but the Papp was increased when presented in NP. SeMet had minimal effects on the electrogenic ion secretion of rat jejunal and colonic mucosae in Ussing chambers. Intra-jejunal injections of SeMet-NPs to rats yielded increased plasma levels of SeMet after 3 h for the SeMet-NPs compared to free SeMet. Overall, there is potential to further develop SeMet-NPs for oral supplementation due to the increased intestinal permeability, versus free SeMet, and the low potential for toxicity.

Hydroxy-Selenomethionine Mitigated Chronic Heat Stress-Induced Porcine Splenic Damage via Activation of Nrf2/Keap1 Signal and Suppression of NFκb and STAT Signal.

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso®, SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.

Efficacy of feeding hydroxy-selenomethionine on plasma and milk selenium in mid-lactation dairy cows.

In this study, we aimed to determine the amount of Se transferred to milk and blood of mid- to late-lactation dairy cows when supplemental Se from hydroxy-selenomethionine (OH-SeMet) was fed compared with an unsupplemented group and a group supplemented with a seleno-yeast (SY). Twenty-four lactating Holstein cows (178 ± 43 d in milk) were used in a complete randomized block design for 91 d (7-d covariate period and 84-d treatment period). Treatments were (1) basal diet with an analyzed Se background of 0.2 mg of Se per kg as-fed (control); (2) basal diet + 0.3 mg of Se/kg as-fed from SY (SY-0.3); (3) basal diet + 0.1 mg of Se/kg as-fed from OH-SeMet (OH-SeMet-0.1); and (4) basal diet + 0.3 mg of Se/kg as-fed from OH-SeMet (OH-SeMet-0.3). During the trial, plasma and milk were analyzed for total Se, and plasma was analyzed for glutathione peroxidase activity. The mean plasma and milk Se concentrations exhibited the same relationship, where OH-SeMet-0.3 resulted in the highest values (142 µg/L of plasma and 104 µg/kg of milk), followed by SY-0.3 (134 µg/L and 85 µg/kg), OH-SeMet-0.1 (122 µg/L and 67 µg/kg), and the control group had the lowest values (120 µg/L and 50 µg/kg). The increment of Se in milk induced by OH-SeMet-0.3 (+54 µg/kg) was 54% higher than that induced by SY-0.3 (+35 µg/kg). Additionally, dietary supplementation of 0.2 mg/kg Se from OH-SeMet in the total mixed ration was estimated to be similar to 0.3 mg/kg Se from SY in the total mixed ration when considering the level of Se in the milk. There was no difference in plasma glutathione peroxidase activity between groups; however, OH-SeMet-0.3 significantly decreased somatic cell count. The results confirmed that supplementation with organic Se increases milk and plasma Se concentrations. Moreover, when administered at the same level of supplementation, OH-SeMet was shown to be more efficient than SY in improving milk quality by increasing Se content and decreasing milk somatic cell count.

Selenomethionine promotes ANXA2 phosphorylation for proliferation and protein synthesis of myoblasts and skeletal muscle growth.

Selenomethionine (Se-Met) has many beneficial effects on higher animals and human, and can regulate cellular physiology through distinct signaling pathways. However, the role and molecular mechanism of Se-Met in skeletal muscle growth remains unclear. In this study, we observed the effects of Se-Met on C2C12 myoblasts and skeletal muscle growth of mice, and explored the corresponding molecular mechanism. Se-Met affected proliferation and protein synthesis of C2C12 myoblasts in a hormesis type of relationship, and had an optimal stimulatory effect at 50 µM concentration. Se-Met also affected mTOR, ANXA2, and PKCα phosphorylation in the same manner. ANXA2 knockdown blocked the stimulation of Se-Met on cell proliferation and protein synthesis and inhibition of Se-Met on autophagy of C2C12 myoblasts. Western blotting analysis showed that PI3K inhibition blocked the stimulation of Se-Met on mTOR phosphorylation. ANXA2 knockdown further blocked the stimulation of Se-Met on PI3K and mTOR phosphorylation. Point mutation experiment showed that ANXA2 mediated the stimulation of Se-Met on the PI3K-mTOR signaling through phosphorylation at Ser26. PKCα interacted with ANXA2, and PKCα knockdown blocked the stimulation of Se-Met on ANXA2 phosphorylation at Ser26. Se-Met addition (7.5mg/kg diet, 4 weeks) increased mouse carcass weight, promoted gastrocnemius skeletal muscle growth and ANXA2 and mTOR phosphorylation in this tissue. Collectively, our findings reveal that Se-Met can promote proliferation and protein synthesis of myoblasts and skeletal muscle growth through ANXA2 phosphorylation.

L-selenomethionine affects liver development and glucolipid metabolism by inhibiting autophagy in zebrafish embryos.

Selenium plays a vital role in cancer prevention, antioxidation, and the growth of humans and other vertebrates. Excessive selenium can cause liver injury and metabolic disorders, which can lead to hepatic disease, but few studies have shown the effects of excessive selenium on liver development and its mechanism in zebrafish embryos. In this study, liver development and glucolipid metabolism were investigated in selenium-stressed zebrafish embryos. Under selenium treatment, transgenic fabp10a-eGFP zebrafish embryos showed reduced liver size, and wild-type zebrafish embryos exhibited steatosis and altered lipid metabolism-related indexes and glucose metabolism-related enzyme activities. In addition, selenium-stressed embryos exhibited damaged mitochondria and inhibited autophagy in the liver. An autophagy inducer (rapamycin) alleviated selenium-induced liver injury and restored the expression of some genes related to liver development and glucolipid metabolism. In summary, our research evaluated liver developmental toxicity and metabolic disorders under selenium stress, and confirmed that autophagy and oxidative stress might involve in the selenium-induced hepatic defects.