Search Results (24)

Tocosh is a traditional Andean food made from fermented potatoes with remarkable nutritional and antibacterial properties. Selenium (Se) is an essential micronutrient associated with antioxidant and anti-inflammatory activities. This study analyses the in vitro glycemic, antioxidant, anti-inflammatory and cytotoxic potential of tocosh supplemented with Se-enriched Saccharomyces cerevisiae biomass produced using various concentrations of sodium selenite (0, 5, 7 and 9 mg/L) over 72 h. For each treatment, the amount of selenium accumulated and the yeast’s ability to incorporate selenium were determined. Se-enriched tocosh from yeast biomass obtained at a concentration of 5 mg/L at 4, 16 and 28 h was used to evaluate the aforementioned bioactive properties. These concentrations promoted greater cell growth and biomass recovery without compromising selenium incorporation. No significant differences were observed in terms of glycemic index and antioxidant capacity in Se-enriched tocosh, but inhibition of NO production was observed in RAW 264.7 cells treated with tocosh enriched with selenium-enriched yeast biomass obtained after 28 h, with an IC₅₀ of 28 mg/mL. Overall, Se-supplemented tocosh exhibited anti-inflammatory properties, highlighting the potential of integrating Se biofortification into traditional Andean foods as a novel approach to address nutrient deficiencies and modulate immune responses. These findings suggest that Se-enriched tocosh could be used as a functional food ingredient or nutraceutical in dietary interventions aimed at reducing chronic inflammatory disorders. Full article

Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS’s anti-CC effects, and SS’s inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca²⁺ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC. Full article

Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment. Full article

Selenium (Se) is an essential trace element for humans and animals, but high-dose supplementation with Se compounds, most notably selenite, may exert cytotoxic and other adverse effects. On the other hand, bacteria, including Escherichia coli (E. coli), are capable of reducing selenite to red elemental Se that may serve as a safer Se source. Here, we examined how a diet of Se-enriched E. coli bacteria affected vital parameters and age-associated neurodegeneration in the model organism Caenorhabditis elegans (C. elegans). The growth of E. coli OP50 for 48 h in medium supplemented with 1 mM sodium selenite resulted in reddening of the bacterial culture, accompanied by Se accumulation in the bacteria. Compared to nematodes supplied with the standard E. coli OP50 diet, the worms fed on Se-enriched bacteria were smaller and slimmer, even though their food intake was not diminished. Nevertheless, given the choice, the nematodes preferred the standard diet. The fecundity of the worms was not affected by the Se-enriched bacteria, even though the production of progeny was somewhat delayed. The levels of the Se-binding protein SEMO-1, which serves as a Se buffer in C. elegans, were elevated in the group fed on Se-enriched bacteria. The occurrence of knots and ruptures within the axons of cholinergic neurons was lowered in aged nematodes provided with Se-enriched bacteria. In conclusion, C. elegans fed on Se-enriched E. coli showed less age-associated neurodegeneration, as compared to nematodes supplied with the standard diet. Full article

The investigation of adipose tissue-derived mesenchymal stem cells (ASCs) has received considerable interest in regenerative medicine. A nontoxic adipogenic induction protocol valid for cells of different mammalian species has not been described. This study aims to establish an adipogenic differentiation protocol suitable for horses, sheep, dogs, murines, and human cells. An optimized rosiglitazone protocol, consisting of 5% fetal calf serum in Dulbecco’s Modified Eagle’s Medium, 10 μg/mL insulin, 0.55 μg/mL transferrin, 6.8 ng sodium selenite, 1 μM dexamethasone, and 1–5 μM of rosiglitazone, is compared to the 3-isobutyl-1-methylxantine (IBMX) protocol, where rosiglitazone was replaced with 0.5 mM IBMX and 0.2 mM indomethacin. Cell viability, cytotoxicity, a morphometric analysis of the lipid, and the expression of adipogenic markers for 14 days were assessed. The data revealed that using 5 µM of rosiglitazone promotes the adipogenic differentiation capacity in horse, sheep, and dog cells compared to IBMX induction. Meanwhile, marked reductions in the cell viability and cell number with the IBMX protocol were detected, and rosiglitazone increased the cell number and lipid droplet size, prevented apoptosis, and upregulated FABP-4 and Leptin expression in the cells of most of the species. Our data revealed that the rosiglitazone protocol improves the adipogenesis of ASCs, together with having less toxicity, and should be considered for cell reproducibility and clinical applications targeting obesity. Full article

Earlier studies have shown that selenomethionine (SM) supplements in broiler breeders had higher deposition in eggs, further reduced the mortality of chicken embryos, and exerted a stronger antioxidant ability in offspring than sodium selenite (SS). Since previous studies also confirmed that Se deposition in eggs was positively correlated with maternal supplementation, this study aimed to directly investigate the antioxidant activities and underlying mechanisms of SS and SM on the chicken hepatocellular carcinoma cell line (LMH). The cytotoxicity results showed that the safe concentration of SM was up to 1000 ng/mL, while SS was 100 ng/mL. In Se treatments, both SS and SM significantly elevated mRNA stability and the protein synthesis rate of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), two Se-containing antioxidant enzymes. Furthermore, SM exerted protective effects in the H₂O₂-induced oxidant stress model by reducing free radicals (including ROS, MDA, and NO) and elevating the activities of antioxidative enzymes, which performed better than SS. Furthermore, the results showed that cotreatment with SM significantly induced apoptosis induced by H₂O₂ on elevating the content of Bcl-2 and decreasing caspase-3. Moreover, investigations of the mechanism revealed that SM might exert antioxidant effects on H₂O₂-induced LMHs by activating the Nrf2 pathway and enhancing the activities of major antioxidant selenoenzymes downstream. These findings provide evidence for the effectiveness of SM on ameliorating H₂O₂-induced oxidative impairment and suggest SM has the potential to be used in the prevention or adjuvant treatment of oxidative-related impairment in poultry feeds. Full article

Cancer is one of the main causes of human death globally and novel chemotherapeutics are desperately required. As a simple selenium oxide, selenite is a very promising chemotherapeutic because of pronounced its dose-dependent tumor-specific cytotoxicity. We previously published a first-in-man systematic phase I clinical trial in patients with cancer (from IV to end-stage) (the SECAR trial) showing that selenite is safe and tolerable with an unexpectable high maximum tolerated dose (MTD) and short half-life. In the present study, we analyzed the selenium species in plasma samples, from the patients participating in the SECAR trial and from various time points and dose cohorts using LC-ICP-MS. In conclusion, selenite, selenosugars, and 1–2 unidentified peaks that did not correspond to any standard, herein denoted ui-selenium, were detected in the plasma. However, trimethylated selenium (trimethylselenonoium) was not detected. The unidentified ui-selenium was eluting close to the selenium-containing amino acids (selenomethionine and selenocysteine) but was not part of a protein fraction. Our data demonstrate that the major metabolite detected was selenosugar. Furthermore, the identification of selenite even long after the administration is remarkable and unexpected. The kinetic analysis did not support that dosing per the body surface area would reduce interindividual variability of the systemic exposure in terms of trough concentrations. Full article

Selenium nanoparticles (SeNPs) are all important for research because they exhibit a higher degree of absorption and lower toxicity than that of their organic and inorganic forms. At present, there are few reports on marine strains that can reduce Se(IV) to generate Se(0). In this study, a strain that reduces sodium selenite to SeNPs with high efficiency was screened from 40 marine strains. The SeNPs-S produced by the whole cells and SeNPs-E produced by the extracellular extract were characterized by FTIR, UV, Raman, XRD and SEM. Based on the results, the two kinds of SeNPs exhibited obvious differences in morphology, and their surfaces were capped with different biomacromolecules. Due to the difference in shape and surface coating, opposite results were obtained for the antibacterial activity of SeNPs-S and SeNPs-E against Gram-positive and Gram-negative bacteria. Both SeNPs-S and SeNPs-E exhibited no obvious cytotoxicity at concentrations up to 100 μg/mL, but SeNPs-E retained lower cytotoxicity when its concentration increased to 200 μg/mL. This is the first report on the detailed difference between the SeNPs produced by whole cells and cell extracts. Full article

Mercury (Hg) is known for its neurotoxicity and is reported to activate microglia cells at low exposure levels. Since mercury decreases the activity of the glutathione and thioredoxin systems, we hypothesize that Hg would, in turn, disrupt microglia homeostasis by interfering with redox regulation of signaling pathways. Thus, in this work, we analyzed the effect of exposure to Hg²⁺ on nuclear translocation and activation of NF-kB (p50) and p38 and pro-inflammatory gene transcription (IL-1ß; iNOS, TNF-alpha) considering the interaction of Hg with the glutathione system and thioredoxin systems in microglial cells. N9 (mouse) microglia cells were exposed to different concentrations of Hg²⁺ and the 24 h EC₅₀ for a reduction in viability was 42.1 ± 3.7 μM. Subsequent experiments showed that at sub-cytotoxic levels of Hg²⁺, there was a general increase in ROS (≈40%) accompanied by a significant depletion (60–90%) of glutathione (GSH) and thioredoxin reductase (TrxR) activity. Upon 6 h of exposure to Hg²⁺, p38 (but not p50) accumulated in the nucleus (50% higher than in control), which was accompanied by an increase in its phosphorylation. Transcript levels of both IL1-ß and iNOS were increased over two-fold relative to the control. Furthermore, pre-exposure of cells to the p38 inhibitor SB 239063 hindered the activation of cytokine transcription by Hg²⁺. These results show that disruption of redox systems by Hg²⁺ prompts the activation of p38 leading to transcription of pro-inflammatory genes in microglia cells. Treatment of N9 cells with NAC or sodium selenite—which caused an increase in basal GSH and TrxR levels, respectively, prevented the activation of p38 and the transcription of pro-inflammatory cytokines. This result demonstrates the importance of an adequate nutritional status to minimize the toxicity resulting from Hg exposure in human populations at risk. Full article

Patulin (PAT) is a toxic fungal metabolite, and oxidative damage was proved to be its important toxicity mechanism. Selenium nanoparticles (SeNPs) were prepared by reducing sodium selenite with chitosan as a stabilizer and used for preventing PAT-induced liver, kidney and gastrointestinal damage. SeNPs have good dispersibility, in vitro antioxidant activity, and are much less cytotoxic than sodium selenite. Cell culture studies indicated that SeNPs can effectively alleviate PAT-induced excessive production of intracellular ROS, the decline of glutathione peroxidase activity, and the suppression of cell viability. Evaluation of serum biochemical parameters, histopathology, oxidative stress biomarkers and activities of antioxidant enzymes in a mouse model showed that pre-treatment with SeNPs (2 mg Se/kg body weight) could ameliorate PAT-induced oxidative damage to the liver and kidneys of mice, but PAT-induced gastrointestinal oxidative damage and barrier dysfunction were not recovered by SeNPs, possibly because the toxin doses suffered by the gastrointestinal as the first exposed tissues exceeded the regulatory capacity of SeNPs. These results suggested that a combination of other strategies may be required to completely block PAT toxicity. Full article

Although selenium nanoparticles (SeNPs) have attracted great attention due to their potential antioxidant activity and low toxicity, the application of SeNPs is still restricted by their poor stability. A combination of polysaccharides and SeNPs is an effective strategy to overcome the limitations. In this study, Polygonatum sibiricum polysaccharide (PSP) was used as a stabilizer to fabricate SeNPs under a simple redox system. Dynamic light scattering, transmission electron microscopy, energy dispersive X-ray, ultraviolet-visible spectroscopy, Fourier transform infrared, and X-ray photoelectron spectrometer were applied to characterize the synthesized PSP-SeNPs. The stability and the antioxidant activity of PSP-SeNPs were also investigated. The results revealed that the zero-valent and well-dispersed spherical PSP-SeNPs with an average size of 105 nm and a negative ζ-potential of −34.9 mV were successfully synthesized using 0.1 mg/mL PSP as a stabilizer. The prepared PSP-SeNPs were stable for 30 days at 4 °C. The decoration of the nanoparticle surface with PSP significantly improved the free radical scavenging ability of SeNPs. Compared to the H₂O₂-induced oxidative stress model group, the viability of PC-12 cells pretreated with 20 μg/mL PSP-SeNPs increased from 56% to 98%. Moreover, PSP-SeNPs exhibited a higher protective effect on the H₂O₂-induced oxidative damage on PC-12 cells and lower cytotoxicity than sodium selenite and SeNPs. In summary, these results suggest the great potential of PSP-SeNPs as a novel antioxidant agent in the food or nutraceuticals area. Full article

Combination of intermittent fasting and chemotherapy has been drawn an increasing attention because of the encouraging efficacy. In this study, we evaluated the anti-cancer effect of combination of glucose limitation and selenite (Se), a representative inorganic form of selenium, that is preferentially accumulated in tumors. Results showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to cystine accumulation, NADPH depletion and the conversion of cystine to cysteine inhibition, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite and imply that combination of selenite and fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer. Full article

Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further clinical application as treatment with radiation and chemotherapy. These functions of selenium are mostly related to oxidation and reduction mechanisms of selenium metabolites. Hydrogen selenide from selenite, and methylselenol (MSeH) from Se-methylselenocyteine (MSeC) and methylseleninicacid (MSeA) are the most reactive metabolites produced reactive oxygen species (ROS); furthermore, these metabolites may involve in oxidizing sulfhydryl groups, including glutathione. Selenite also reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus. However, a more pronounced effect was shown in the subsequent treatment of sodium selenite with chemotherapy and radiation therapy. High doses of sodium selenite were effective to increase radiation therapy and chemotherapy, and further to reduce radiation side effects and drug resistance. In our study, advanced cancer patients can tolerate until 5000 μg of sodium selenite in combination with radiation and chemotherapy since the half-life of sodium selenite may be relatively short, and, further, selenium may accumulates more in cancer cells than that of normal cells, which may be toxic to the cancer cells. Further clinical studies of high amount sodium selenite are required to treat advanced cancer patients. Full article

The aim of this study was to prepare a biomimetic selenium substituted calcium phosphate system for potential application in osteosarcoma therapy. Calcium phosphate (CaP) systems substituted with selenite ions were prepared by the wet precipitation method, using biogenic CaCO₃ (derived from cuttlefish bone), CO(NH₂)₂-H₃PO₄, and Na₂SeO₃·5H₂O as reagents. Starting reaction mixtures were prepared based on the formula for selenite-substituted hydroxyapatite, Ca₁₀(PO₄)_6-x(SeO₃)_x(OH)₂, with Ca/(P + Se) molar ratio of 1.67 and Se/(P + Se) molar ratio of: 0, 0.01, 0.05, and 0.10, respectively. The prepared CaP powders were characterized by Fourier transform infrared spectrometry, elemental analysis, scanning electron microscopy, X-ray powder diffraction analysis and Rietveld refinement studies. Phase transformation and ion release were analyzed during 7 days of incubation in simulated body fluid at 37 °C. The metabolic activity of healthy and osteosarcoma cell lines was assessed by cell cytotoxicity and viability test. The as-prepared powders were composed of calcium-deficient carbonated hydroxyapatite (HAp), octacalcium phosphate (OCP), and amorphous calcium phosphate (ACP). Along with the selenite substitution, the presence of Sr²⁺, Na⁺, and Mg²⁺ was detected as a result of using cuttlefish bone as a precursor for Ca²⁺ ions. Inductively coupled plasma mass spectrometry analysis showed that the Se/(P + Se) molar ratios of selenite substituted powders are lower than the nominal ratios. Heat treated powders were composed of HAp, α-tricalcium phosphate (α-TCP) and β-tricalcium phosphate (β-TCP). Doping CaP structure with selenite ions improves the thermal stability of HAp. The powder with the Se/(P + Se) molar ratio of 0.007 showed selective toxicity to cancer cells. Full article

Her/2+ breast cancer accounts for ~25% mortality in women and overexpression of Her/2 leads to cell growth and tumor progression. Trastuzumab (Tz) with Taxane is the preferred treatment for Her/2+ patients. However, Tz responsive patients often develop resistance to Tz treatment. Herein, redox selenides (RSe-) were covalently linked to Tz using a selenium (Se)-modified Bolton–Hunter Reagent forming Seleno-Trastuzumab (Se-Tz; ~25 µgSe/mg). Se-Tz was compared to Tz and sodium selenite to assess the viability of JIMT-1 and BT-474 cells. Comparative cell viability was examined by microscopy and assessed by fluorometric/enzymatic assays. Se-Tz and selenite redox cycle producing superoxide (O₂^•−) are more cytotoxic to Tz resistant JIMT-1 and Tz sensitive BT-474 cells than Tz. The results of conjugating redox selenides to Tz suggest a wider application of this technology to other antibodies and targeting molecules. Full article