Response surface methodology optimizes selenium inhibition of prostate cancer PC-3 cell viability.

BACKGROUND: The rising incidence of prostate cancer in the U.S. necessitates innovative therapeutic approaches to this disease. Though extensive research has studied Selenium as an anticarcinogen against prostate cancer, results have varied due to overlooked experimental confounds. Recent studies have identified differential effects of various selenium compounds on prostate cancer cells. This study leverages Mixture Design Response Surface Methodology to characterize the ideal combination of select Se forms against the PC-3 prostate cancer cell line. METHODS: The PC-3 cell line was chosen as a model for its representation of advanced-stage malignancy. Three Se compounds-sodium selenite, methylseleninic acid, and nano-selenium-were selected for their promising antineoplastic potential. Nano-Se particles were synthesized and subsequently characterized by transmission electron microscopy. Cells were cultured, treated with Se compounds, and assessed for viability using an Alamar Blue Assay. IC50 values of individual Se compounds were determined, and treatment combinations evaluated. In collaboration with statical modeling experts, MDRSM was utilized to optimize Se compound combinations. RESULTS: Absolute IC50 values were identified for methylseleninic acid (5.01 µmol/L), sodium selenite (13.8 µmol/L), and nano-selenium (14.6 µmol/L). Combining methylseleninic acid and sodium selenite resulted in only 5% PC-3 cell viability, whereas individual treatments reduced viability by approximately 45%. Among the tested mixtures, the 50:50 combination of MSA and sodium selenite most effectively decreased PC-3 cell viability. Regression analysis indicated the special cubic model had a strong fit (multiple r² = 0.9853), predicting maximum cell viability reduction from the methylseleninic acid and selenite mixture. CONCLUSION: The specific form of Selenium plays a pivotal role in determining its physiological effects and therapeutic potential against prostate cancer. All three selenium compounds showed variable antineoplastic effects, with a 50:50 mixture of methylseleninic acid and selenite exhibiting optimal results. Nano-selenium, when combined with selenite, showed no additive effect, implying a shared mechanism of action. Our research underscores the critical need to consider Se compound forms as distinct entities in prostate cancer treatment and encourages further exploration of Se compounds against prostate cancer.

Protecting spring wheat plants using selenium and pesticides.

The research was carried out in order to find ways to optimize the system of protection of spring wheat crops. In the conducted studies, the effect of combinations of sodium selenite and various pesticides, differing in the specifics of action and biological activity, on the yield and quality of spring wheat of the Yubileinaya 80 variety was studied. Currently, there is a need to achieve a sufficient effect of the action of chemical plant protection products and to obtain a minimum impact on human health and the environment. The purpose of the research is to study the influence of various combinations of chemical plant protection products and methods of using sodium selenite on the yield and grain quality indicators of spring wheat variety Yubileinaya 80. The studies were carried out under the conditions of a vegetative experiment with spring wheat variety Yubileinaya 80. Two methods of using sodium selenite and chemical plant protection agents of different specifics of action were studied: fungicide, herbicide, and insecticide, which were applied in different combinations and at different times. As a result of the studies, the phytotoxicity of the studied preparations of chemical plant protection was revealed, which apparently manifests itself as a result of inhibition of the morphometric indicators of the growth of the root system and vegetative organs of wheat plants, resulting in a violation of the processes of accumulation of assimilates and their outflow to the reproductive organs. Optimal combinations of pesticides and sodium selenite have been established, allowing to obtain reliable changes in yield and quality indicators of wheat grain. It was revealed that the use of selenium treatment before sowing seeds contributed to a decrease in the phytotoxicity of the studied pesticides, as a result of stimulating the processes of absorption by plants and the redistribution of nitrogen to the reproductive organs of wheat, which had a positive effect not only on the yield and quality of spring wheat of the Yubileynaya 80 variety, but also on the external surface microstructure of the fruit shell of the grain. The noted features of the surface of the fruit shell of the grain will reduce losses during grain processing and obtain processed products from such grain of higher quality.

Effects of sodium selenite, yeast selenium, and nano-selenium on toxicity, growth, and selenium bioaccumulation in Lucilia sericata maggots.

In this study, we investigated the effects of different types of selenium (Se) (sodium selenite [SS], yeast selenium [YS], and nano-selenium [NS]) on the toxicity, growth, Se accumulation, and transformation of Lucilia sericata maggots (LSMs). We found that the 50% lethal concentration of LSMs exposed to SS was 2.18 and 1.96 times that of YS and NS, respectively. LSM growth was significantly promoted at exposure concentrations of 10-50 mg kg-1 in group SS and 10-30 mg kg-1 in group YS, whereas NS inhibited LSMs growth at all concentrations (p < 0.05). Total Se content in LSMs, conversion efficiency to organic and other forms of Se, and bioaccumulation factor of Se were the highest in the SS group when exposed to 50 mg kg-1 (81.6 mg kg-1, 94.6%, and 1.63, respectively). Transcriptomic results revealed that LSMs significantly upregulated the amino acid (alanine, aspartate, glutamic, and tyrosine) and tricarboxylic acid cycle signaling pathways (p < 0.05) on exposure to Se, resulting in a significant increase in LSMs biomass and quality. In conclusion, our study indicates that LSMs exhibit good tolerance to SS and can convert it into bioorganic or other forms of Se.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

Ameliorating Effect of Sodium Selenite on Developmental and Molecular Response of Bovine Cumulus-Oocyte Complexes Matured in Vitro Under Heat Stress Condition.

Selenium (Se), an essential trace element, plays an important role in the antioxidative defense mechanism, and it has been proven to improve fertility and reproductive efficiency in dairy cattle. The present study evaluated the potential protective action of Se supplement of in vitro maturation (IVM) media on the maturation and subsequent development of bovine cumulus-oocyte complexes (COCs) exposed to heat stress (HS). The treatment with Se improved the viability of cumulus cells (CCs) and oocytes (P < 0.05). The proportion of oocytes reached metaphase II (MII) and those arrested at metaphase I (MI) was greater and lower in treatment than control respectively (P < 0.05). Supplementation with Se increased the percentage of cleaved embryos, total blastocysts, and blastocyst/cleavage ratio (P < 0.05). Moreover, the upregulation of CCND1, SEPP1, GPX-4, SOD, CAT, and downregulation of GRP78, CHOP, and BAX in both Se-treated CCs and oocytes were recorded. The upregulation of NRF2 was detected in Se-treated CCs other than in oocytes, which showed upregulation of IGF2R and SOX-2 as the markers of quality as well. Se supplement in IVM media improved the viability, maturation, and the level of transcripts related to antioxidant defense and quality of heat-treated oocytes, which coincided with greater subsequent development outcomes. Se ameliorated the viability of CCs along with upregulation of antioxidative candidate gene expression and downregulation of apoptosis-related ones to support their protective role on restoring the quality of oocytes against compromising effects of HS.

Comparison of Sodium Selenite and Selenium-Enriched Spirulina Supplementation Effects After Selenium Deficiency on Growth, Tissue Selenium Concentrations, Antioxidant Activities, and Selenoprotein Expression in Rats.

Selenium contributes to physiological functions through its incorporation into selenoproteins. It is involved in oxidative stress defense. A selenium deficiency results in the onset or aggravation of pathologies. Following a deficiency, the repletion of selenium leads to a selenoprotein expression hierarchy misunderstood. Moreover, spirulina, a microalga, exhibits antioxidant properties and can be enriched in selenium.. Our objective was to determine the effects of a sodium selenite or selenium-enriched spirulina supplementation. Thirty-two female Wistar rats were fed for 12 weeks with a selenium-deficient diet. After 8 weeks, rats were divided into 4 groups and were fed with water, sodium selenite (20 µg Se/kg body weight), spirulina (3 g/kg bw), or selenium-enriched spirulina (20 µg Se/kg bw + 3 g spirulina/kg bw). Another group of 8 rats was fed with normal diet during 12 weeks. Selenium concentration and antioxidant enzyme activities were measured in plasma, urine, liver, brain, kidney, heart, and soleus. Expression of GPx (1, 3), Sel (P, S, T, W), SEPHS2, TrxR1, ApoER2, and megalin were quantified in liver, kidney, brain, and heart. We showed that a selenium deficiency leads to a growth delay, reversed by selenium supplementation despite a minor loss of weight in week 12 for SS rats. All tissues displayed a decrease in selenium concentration following deficiency. The brain seemed protected. We demonstrated a hierarchy in selenium distribution and selenoprotein expression. A supplementation of sodium selenite improved GPx activities and selenoprotein expression while a selenium-enriched spirulina was more effective to restore selenium concentration especially in the liver, kidney, and soleus.

A study on the effectiveness of sodium selenite in treating cadmium and perfluoro octane sulfonic (PFOS) poisoned zebrafish (Danio rerio).

Perfluoro octane sulfonate (PFOS) and cadmium (Cd) are toxic elements in the environment. As a micronutrient trace element, selenium (Se) can mitigate the adverse effects induced by PFOS and Cd. However, few studies have examined the correlation between Se, PFOS and Cd in fish. The present study focused on the antagonistic effects of Se on PFOS+Cd-induced accumulation in the liver of zebrafish. The fish was exposed to PFOS (0.08mg/L), Cd (1mg/L), PFOS+ Cd (0.08 mg/L PFOS+1 mg/L Cd), L-Se (0.07mg/L Sodium selenite +0.08mg/L PFOS+1mg/L Cd), M-Se (0.35mg/L Sodium selenite + 0.08mg/L PFOS+ 1 mg/L Cd), H-Se (1.75 mg/L Sodium selenite + 0.08 mg/L PFOS+ 1mg/L Cd) for 14d. The addition of selenium to fish exposed to PFOS and Cd has been found to have significant positive effects. Specifically, selenium treatments can alleviate the adverse effects of PFOS and Cd on fish growth, with a 23.10% improvement observed with the addition of T6 compared to T4. In addition, selenium can alleviate the negative effects of PFOS and Cd on antioxidant enzymes in zebrafish liver, thus reducing the liver toxicity caused by PFOS and Cd. Overall, the supplementation of selenium can reduce the health risks to fish and mitigate the injuries caused by PFOS and Cd in zebrafish.

Combined Transcriptomics and Metabolomics Analysis Reveals the Effect of Selenium Fertilization on Lycium barbarum Fruit.

As a beneficial nutrient and essential trace element, selenium plays a significant role in plant growth functions and human protein biosynthesis. Plant selenium enrichment is mainly obtained from both natural soil and exogenous selenium supplementation, while human beings consume selenium-enriched foods for the purposes of selenium supplementation. In this study, different types of selenium fertilizers were sprayed onto Lycium barbarum in Ningxia, and transcriptomics and metabolomics techniques were used to explore the effects of selenium on the fruit differentials and differential genes in Lycium barbarum. Taking the "Ning Qiyi No.1" wolfberry as the research object, sodium selenite, nano-selenium, and organic selenium were sprayed at a concentration of 100 mg·L-1 three times from the first fruiting period to the harvesting period, with a control treatment comprising the spraying of clear water. We determined the major metabolites and differential genes of the amino acids and derivatives, flavonoids, and alkaloids in ripe wolfberries. We found that spraying selenium significantly enhanced the Lycium barbarum metabolic differentiators; the most effective spray was the organic selenium, with 129 major metabolic differentiators and 10 common metabolic pathways screened after spraying. Nano-selenium was the next best fertilizer we screened, with 111 major metabolic differentiators, the same number as organic selenium in terms of differential genes and common metabolite pathways. Sodium selenite was the least effective of the three, with only 59 of its major metabolic differentials screened, but its differential genes and metabolites were enriched for five common pathways.

Transcriptomic characterization of interactions between sodium selenite and coenzyme Q10 on preventing cadmium-induced testicular defects.

The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.

Response of rumen fermentation and microbiota to dietary supplementation of sodium selenite and bio-nanostructured selenium in lactating Barki sheep.

Dietary selenium (Se) sources affects the structure of the rumen microbial community and rumen fermentation. This study evaluated the effects of sodium selenite (SS) and bio-nanostructured selenium (SeNSM) on rumen fermentation and structure of rumen microbial community of lactating Barki ewes. Twenty one lactating Barki ewes were assigned into three groups based on their body weight and milk yield. The experiment lasted for 50 days, whenever, the control group was fed basal diet; group SS received basal diets plus sodium selenite as inorganic source of Se; and group SeNSM received basal diet plus organic selenium bio-nanostructured. Ruminal pH and volatile Fatty Acids (VFA) was lower (P < 0.05) in SeNSM group compared to control. Principle Coordinate Analysis separated the microbial communities into three clusters based on feeding treatment. The bacterial community was dominated by phylum Bacteroidetes and Firmicutes that were affected (P < 0.05) by Se sources. Specifically Bacteriodetes was higher (P < 0.05) in SS and SeNSM groups; and Firmicutes was higher (P < 0.05) in the control group. Moreover, the predominant bacterial genera were Prevotella, Rikenellaceae RC9 gut group, Unclassified_Bacteroidales, which were higher (P < 0.05) in SeNSM group. The methanogenic community belonged to phylum Euryarchaeota and was significantly decreased (P < 0.05) by Se supplementation. Principal component analysis based on rumen fermentation parameters, and relative abundances of bacteria and methanogens revealed three distinct clusters. These findings suggest that Se supplementation affected the relative abundances of dominant bacterial groups, declined rumen methanogens and SeNSM supplementation showed some positive impacts on some fibrolytic bacteria.

Sodium selenite (Na2SeO3) attenuates T-2 toxin-induced iron death in LMH cells through the ROS/PI3K/AKT/Nrf2 pathway.

T-2 toxin, is a monotrichous mycotoxin commonly found in animal feed and agricultural products that can damage tissues and organs through oxidative stress. Selenium is a trace element with favorable antioxidant effects. However, it is unclear whether T-2 toxin-induces ferroptosis in LMH cells and whether Na2SeO3 has a protective role in this process. To investigate the process of hepatic injury by T-2 toxin and its antagonistic effect by Na2SeO3, we used 20 ng/mL T-2 toxin as well as 160 nmol/L Na2SeO3 to treat the LMH cells. The results demonstrated that exposure to the T-2 toxin induced iron death by increasing the quantity of ROS, leading to oxidative damage, decreasing the quantities of SOD, GPx, and T-AOC, and increasing the accumulation of MDA and H2O2, which resulted in the accumulation of Fe2+ and the down-regulation of the manifestation of linked genes and proteins including FTH1, Gpx4, NQO-1, and HO-1. After the addition of Na2SeO3, the PI3K/AKT/Nrf2 pathway is activated by regulating the selenoproteins gene level, and the above abnormal changes are reversed. In summary, Na2SeO3 alleviated T-2 toxin-induced iron death via the PI3K/AKT/Nrf2 pathway. These study not only broaden the cytotoxic knowledge regarding T-2 toxin, but also serve as a foundation for the use of Na2SeO3 in daily life.

Nano-Selenium inhibited antibiotic resistance genes and virulence factors by suppressing bacterial selenocompound metabolism and chemotaxis pathways in animal manure.

Numerous antibiotic resistance genes (ARGs) and virulence factors (VFs) found in animal manure pose significant risks to human health. However, the effects of graphene sodium selenite (GSSe), a novel chemical nano-Selenium, and biological nano-Selenium (BNSSe), a new bioaugmentation nano-Se, on bacterial Se metabolism, chemotaxis, ARGs, and VFs in animal manure remain unknown. In this study, we investigated the effects of GSSe and BNSSe on ARGs and VFs expression in broiler manure using high-throughput sequencing. Results showed that BNSSe reduced Se pressure during anaerobic fermentation by inhibiting bacterial selenocompound metabolism pathways, thereby lowering manure Selenium pollution. Additionally, the expression levels of ARGs and VFs were lower in the BNSSe group compared to the Sodium Selenite and GSSe groups, as BNSSe inhibited bacterial chemotaxis pathways. Co-occurrence network analysis identified ARGs and VFs within the following phyla Bacteroidetes (genera Butyricimonas, Odoribacter, Paraprevotella, and Rikenella), Firmicutes (genera Lactobacillus, Candidatus_Borkfalkia, Merdimonas, Oscillibacter, Intestinimonas, and Megamonas), and Proteobacteria (genera Desulfovibrio). The expression and abundance of ARGs and VFs genes were found to be associated with ARGs-VFs coexistence. Moreover, BNSSe disruption of bacterial selenocompound metabolism and chemotaxis pathways resulted in less frequent transfer of ARGs and VFs. These findings indicate that BNSSe can reduce ARGs and VFs expression in animal manure by suppressing bacterial selenocompound metabolism and chemotaxis pathways.

Involvement of IGF1 in endoplasmic reticulum stress contributes to cataract formation through regulating Nrf2/NF-κB signaling.

Endoplasmic reticulum (ER) stress is reportedly involved in the development of ophthalmic diseases. This study aimed to investigate the role and potential mechanism of insulin-like growth factor 1 (IGF1) in ER stress. A mouse cataract model was constructed by subcutaneous injection of sodium selenite, and sh-IGF1 was used to evaluate the effect of silencing IGF1 on cataract progression. Slit-lamp and histological examination of the lens were performed to examine lens damage. The regulatory effects of IGF1 on inflammatory responses, oxidative stress, and ER stress were evaluated using ELISA, reverse transcription-quantitative PCR (RT-qPCR), and immunoblotting analysis. Tunicamycin was used to induce ER stress in the lens of epithelial cells. The NF-E2 related factor-2 (Nrf2) inhibitor ML385 and nuclear factor-κB (NF-κB) agonist diprovocim were used to confirm whether IGF1 regulates inflammation and ER stress through Nrf2/NF-κB signaling. Silencing IGF1 alleviated lens damage and reduced lens turbidity in the cataract mice. Silencing IGF1 inhibited inflammatory response, oxidative stress and ER stress response. Meanwhile, IGF1 was highly expressed in sodium selenite-treated lens epithelial cells. The ER stress agonist tunicamycin suppressed cell viability as well as induced ER stress, oxidative stress and inflammation. Silencing IGF1 increased cell viability, EdU-positive rate and migration. Also, silencing of IGF1 reduced inflammation and ER stress via regulating Nrf2/NF-κB pathway. This study reveals silencing IGF1 attenuated cataract through regulating Nrf2/NF-κB signaling, which shares novel insights into the underlying mechanism of cataract and provides potential therapeutic target for cataract.

Sodium selenite preserves rBM-MSCs' stemness, differentiation potential, and immunophenotype and protects them against oxidative stress via activation of the Nrf2 signaling pathway.

BACKGROUND: The physiological level of reactive oxygen species (ROS) is necessary for many cellular functions. However, during the in-vitro manipulations, cells face a high level of ROS, leading to reduced cell quality. Preventing this abnormal ROS level is a challenging task. Hence, here we evaluated the effect of sodium selenite supplementation on the antioxidant potential, stemness capacity, and differentiation of rat-derived Bone Marrow MSCs (rBM-MSCs) and planned to check our hypothesis on the molecular pathways and networks linked to sodium selenite's antioxidant properties. METHODS: MTT assay was used to assess the rBM-MSCs cells' viability following sodium selenite supplementation (concentrations of: 0.001, 0.01, 0.1, 1, 10 µM). The expression level of OCT-4, NANOG, and SIRT1 was explored using qPCR. The adipocyte differentiation capacity of MSCs was checked after Sodium Selenite treatment. The DCFH-DA assay was used to determine intracellular ROS levels. Sodium selenite-related expression of HIF-1α, GPX, SOD, TrxR, p-AKT, Nrf2, and p38 markers was determined using western blot. Significant findings were investigated by the String tool to picture the probable molecular network. RESULTS: Media supplemented with 0.1 µM sodium selenite helped to preserve rBM-MSCs multipotency and keep their surface markers presentation; this also reduced the ROS level and improved the rBM-MSCs' antioxidant and stemness capacity. We observed enhanced viability and reduced senescence for rBM-MSCs. Moreover, sodium selenite helped in rBM-MSCs cytoprotection by regulating the expression of HIF-1 of AKT, Nrf2, SOD, GPX, and TrxR markers. CONCLUSIONS: We showed that sodium selenite could help protect MSCs during in-vitro manipulations, probably via the Nrf2 pathway.

Transcriptome analysis reveals different mechanisms of selenite and selenate regulation of cadmium translocation in Brassica rapa.

Selenium (Se) inhibits cadmium (Cd) root-to-shoot translocation and accumulation in the shoots of pak choi; however, the mechanism by which Se regulates Cd retention in roots is still poorly understood. A time-dependent hydroponic experiment was conducted to compare the effects of selenite and selenate on Cd translocation and retention in the roots. The underlying mechanisms were investigated regarding Se biotransformation and metal transportation in roots using HPLC and transcriptome analyses. Selenite showed reducing effects on Cd translocation and accumulation in shoots earlier than selenate. Selenite is mainly biotransformed into selenomethionine (80% of total Se in roots) at 72 h, while SeO42- was the dominant species in the selenate treatments (68% in shoots). Selenite up-regulated genes involved in the biosynthesis of lignin, suberin, and phytochelatins and those involved in stress signaling, thereby helping to retain Cd in the roots, whereas essentially, selenate had opposite effects and impaired the symplastic and apoplastic retention of Cd. These results suggest that cell-wall reinforcement and Cd retention in roots may be the key processes by which Se regulates Cd accumulation, and faster biotransformation into organic seleno-compounds could lead to earlier effects.

Antioxidants supplementation improves the quality of in vitro produced ovine embryos with amendments in key development gene expressions.

The present study assessed the effects of supplementation of different antioxidants on oocyte maturation, embryo production, reactive oxygen species (ROS) production and expression of key developmental genes. In this study, using ovine as an animal model, we tested the hypothesis that antioxidant supplementation enhanced the developmental competence of oocytes. Ovine oocytes aspirated from local abattoir-derived ovaries were subjected to IVM with different concentrations of antioxidants [(Melatonin, Ascorbic acid (Vit C), alpha-tocopherol (Vit E), Sodium selenite (SS)]. Oocytes matured without any antioxidant supplementation were used as controls. The oocytes were assessed for maturation rates and ROS levels. Further, embryo production rates in terms of cleavage, blastocysts and total cell numbers were evaluated after performing in vitro fertilization. Real-Time PCR analysis was used to evaluate the expression of stress related gene (SOD-1), growth related (GDF-9, BMP-15), and apoptosis-related genes (BCL-2 and BAX). We observed that maturation rates were significantly higher in alpha-tocopherol (100 µM; 92.4%) groups followed by melatonin (30 µM; 89.1%) group. However, blastocyst rates in ascorbic acid (100 µM; 19.5%), melatonin (30 µM; 18.4%), alpha-tocopherol (100 µM; 18.2%), and sodium selenite (20 µM; 16.9%) groups were significantly higher (P 0.05) than that observed in the control groups. Total cell numbers in blastocysts in the melatonin, ascorbic acid and alpha-tocopherol groups were significantly higher than those observed in sodium selenite and control groups. ROS production was reduced in groups treated with melatonin (30 µM), vitamin C (100 µM), sodium selenite (20 µM) and α-tocopherol (200 µM) compared with that observed in the control group. Supplementation of antioxidants caused the alterations in mRNA expression of growth, stress, and apoptosis related gene expression in matured oocytes. The results recommend that antioxidants alpha-tocopherol (200 µM), sodium selenite (40 µM), melatonin (30 µM) and ascorbic acid (100 µM) during IVM reduced the oxidative stress by decreasing ROS levels in oocytes, thus improving embryo quantity and quality.

Selenium toxicity and bioaccumulation in selenium-enriched fly (Chrysomya megacephala) maggots.

Selenium (Se) is an essential trace element for human health, and as a potential animal feed, the Chrysomya megacephala (Fabricius) fly is rich in protein and fat. By using different concentrations of sodium selenite (0, 30, 50, 70 mg kg-1), the possibility of biological Se enrichment in C. megacephala (Fabricius) maggots (CMMs) was investigated. The accumulation, Se speciation, enzymatic activity, and concentrations of copper (Cu), zinc (Zn), chromium (Cr), and cadmium (Cd) in the maggots were also determined. Transcriptomics was also used to investigate the mechanism of the Se response to CMM genes. The results showed that the CMMs had a survival rate of > 80% at Se exposure concentrations ranging from 0 to 100 mg kg-1. The optimal concentration of sodium selenite for CMM growth was 50 mg kg-1, and the weight, protein content, and total Se accumulation of the larvae (10.8 g, 53.5%, and 72.6 ± 3.36 mg kg-1 (DW), respectively) were considerably higher than the control and other exposure doses (p < 0.05). In addition, Se improved the ability of maggots to absorb Cu and Zn, decreased malondialdehyde (MDA) and lipid peroxidation, but improved the antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, Se negatively affected the absorption of Cd and Cr. According to the transcriptomic findings, Se supplementation can boost protein synthesis and control both antioxidant and non-antioxidant enzyme activity in CMMs. Therefore, our findings showed that Se-enriched CMMs may counteract the toxicity of Cd and Cr, and Se is an effective supplement for improving the consumption safety of cultured animals fed containing CMMs.

High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer.

Selenium is a promising multi-target chemotherapeutic agent with controversial clinical results. Hence, reassessing the anticancer effects of Se is necessary to clearly understand the potential of high-dose selenium in cancer treatment. Here, we observed that high-dose sodium selenite (SS) significantly decreased the proliferation and increased the death of ovarian cancer cells, mediated by an increased generation of reactive oxygen species. Notably, high-dose SS decreased the levels of glutathione peroxidase (GPx), a selenoprotein with antioxidant properties, without altering other selenoproteins. Furthermore, high-dose SS triggered lipid peroxidation and ferroptosis, a type of iron-dependent cell death, due to dysregulated GPx4 pathways. We demonstrated that intravenous high-dose SS significantly reduced the tumor growth and weight in SKOV3-bearing mice. Consistent with our in vitro results, mice with SKOV3 cells treated with high-dose SS showed decreased GPx4 expression in tumors. Therefore, we highlight the significance of high-dose SS as a potential chemotherapeutic agent for ovarian cancer. High-dose SS-mediated ferroptotic therapy integrating glutathione depletion and ROS generation is a promising strategy for cancer therapy.

Sodium Selenite Modulates Global Activation of Proinflammatory M1-like Macrophages, Necroinflammation and M1-like/M2-like Dichotomy at the Onset of Human Type 1 Diabetes.

AIM: The study aims to show that sodium selenite (Ss) would have an immunomodulatory effect on the functional activity of proinflammatory macrophages (Mφs) during their extended extracellular activation at the onset of human type 1 diabetes (T1D). BACKGROUND: Exacerbated activation of proinflammatory "M1" macrophages (Mφs) can promote chronic local pancreatic islet inflammation and T1D development. OBJECTIVE: We investigated the ex vivo effects of Ss on the immune modulation of global/extended activation of human proinflammatory M1-like Mφs. METHODS: Experiments were carried out on primary monocytes-derived Mφs (MDMs). RESULTS: The levels of IL-1ß, TNF-α, H2O2 and intracellular free calcium ions (ifCa2+), and the ratios of IL-1ß-to-IL-10 and TNF-α-to-IL-10 were markedly increased in T1D Mφs than in healthy control Mφs. Conversely, both IL-10 production and arginase 1 (ARG1) activity were downregulated in T1D Mφs. Additionally, Ss treatment induced a marked downregulation of respiratory burst, ifCa2+ levels, M1-like Mφ-associated inducible nitric oxide (NO) synthase (iNOS) activity, cell necrosis and related necroinflammation biomarkers, including IL-1ß and TNF-α, CD14 expression, and the ratios of iNOS-to-ARG1, IL-1ß-to-IL-10, and TNF-α-to-IL-10. Moreover, Ss upregulated anti-inflammatory "M2-like" Mφ activity as demonstrated by ARG1 activity and IL-10 production, as well as phagocytosis capacity. CONCLUSION: Ss exerts a potent immunomodulatory role on functional activities of human proinflammatory T1D M1-like Mφs subjected to extended activation, as well as on the M1-like/M2-like dichotomy. Additionally, the current study provides a novel therapeutic approach using Ss to promote the anti-inflammatory function of Mφs at the onset of T1D.

Sodium Selenite Diminished the Regulatory T Cell Differentiation In Vitro.

Sodium selenite modulates the activity of lymphocytes. It negatively regulates the suppressive activity of cells and increases the immune response. In this study, we evaluated whether the regulatory T cell differentiation was modulated by sodium selenite. The percentages of CD4+CD25+Foxp3+, CD4+CD25+, and CD4+CTLA-4+ cells in CD4+ T cells cultures stimulated with IL-2 and TGF-ß in the presence or absence of selenium, in the form of sodium selenite (2.0×10-6M), were evaluated by flow cytometry. The mRNA expression of TET2/3 enzymes and IL-10 was analyzed by RT-qPCR and the levels of IL-10 were measured by an ELISA. We observed a decrease in CD4+CD25+Foxp3+ and CD4+CTLA-4+ cells in presence of selenium. However, normal percentages were reached again after selenium removal. An increase in CD4+CTL4-4+ cells was detected in selenium-primed cell cultures in absence of IL-2 and TGF-ß. In addition, we observed a decrease in TET3 in presence of selenium. Finally, we observed an augment in IL-10 transcription and protein levels and relative expression of TET2 in cultures exposed to selenium. We suggest that selenium reversibly affects the regulatory T cell differentiation in vitro. Likewise, selenium may modulate Treg percentages promoting optimal immune responses and, at the same time, the expression of specific suppressor molecules.