Ultrasmall MnSe Nanoparticles as T1-MRI Contrast Agents for In Vivo Tumor Imaging.

Magnetic resonance imaging (MRI) has excellent potential in the clinical monitoring of tumors because it can provide high-resolution soft tissue imaging. However, commercial contrast agents (CAs) used in MRI still have some problems such as potential toxicity to the human body, low relaxivity, and a short MRI acquisition window. In this study, ultrasmall MnSe nanoparticles are synthesized by living Staphylococcus aureus cells. The as-prepared MnSe nanoparticles are monodispersed with a uniform particle size (3.50 ± 0.52 nm). Due to the ultrasmall particle size and good water solubility, the MnSe nanoparticles exhibit in vitro high longitudinal relaxivity properties (14.12 ± 1.85 mM-1·s-1). The CCK-8 colorimetric assay, histological analysis, and body weight results show that the MnSe nanoparticles do not have appreciable toxicity on cells and organisms. Besides, the MnSe nanoparticles as T1-MRI CAs offer a long MRI acquisition window to tumor imaging (∼7 h). This work provides a promising T1-MRI CA for clinical tumor imaging and a good reference for the application of functional MnSe nanoparticles in the biomedicine field.

Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo.

The deficiency of selenium has been found in clinical IBD patients and supplementation selenium is recognized as beneficial for colitis treatment. In this study, an organic selenium compound-selenylation α-D-1,6-glucan (sCPA) was prepared, and the effect of sCPA on DSS induced colitis mice was investigated. The results suggested that sCPA prevented the weight loss, colon length shortening, and stool loose of colitis mice. It protected colon mucosal barrier by promoting tight junction protein ZO-1 and Occludin expression. Moreover, sCPA reduced oxidative stress via regulating SOD and MDA levels, and decreased the contents of inflammatory proteins NF-κB and NLRP3 and adjusted TNF-α, IFN-γ, IL-1ß, and IL-10 inflammatory cytokines. Furthermore, sCPA repaired intestinal microbiota composition especially Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria that altered by DSS in colitis mice. Meanwhile, SCFAs produced by gut microbiota were restored by sCPA close to the level in the normal group. In conclusion, these findings indicated that the sCPA might be a potential dietary selenium supplementation for the prevention and treatment of colitis.

Food Sources of Selenium and Its Relationship with Chronic Diseases.

Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.

Maternal supplementation of organic selenium during gestation improves sows and offspring antioxidant capacity and inflammatory status and promotes embryo survival.

Selenium (Se) is an essential trace element in humans and sows, having a biological function mediated in part by its incorporation into selenoproteins. This study was conducted to investigate the effects of maternal 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), an organic Se source, on reproductive performance, antioxidant capacity and inflammatory status of sows and their offspring. Forty-three Landrace × Yorkshire sows were randomly allocated to receive one of the following three diets during gestation: control diet (control, basal diet, n = 15), sodium selenite (Na2SeO3) supplemented diet (Na2SeO3, basal diet + Na2SeO3 at 0.3 mg Se per kg, n = 13), and HMSeBA supplemented diet (HMSeBA, basal diet + HMSeBA at 0.3 mg Se per kg, n = 15). Blood samples of sows and piglets, placentas and piglet liver samples were analyzed for selenium status, antioxidant capacity and inflammatory cytokines. Results showed that, as compared to the control group, HMSeBA supplementation increased the number of born alive piglets and plasma concentrations of total selenium and selenoprotein P in both sows and piglets. Besides, the activities of antioxidant enzymes in the blood of sows, umbilical cord and piglets, placentas and piglets' liver were increased by dietary HMSeBA supplementation as compared to the control group, while malondialdehyde concentration (p < 0.05) was decreased in the blood of sows, umbilical cord and newborn piglets. In addition, maternal HMSeBA intake during gestation up-regulated antioxidant-related selenoprotein gene expression in the placenta (GPx2, GPx3, p < 0.05) and in the liver of newborn piglets (GPx1, GPx2, GPx3, TXNRD2, p < 0.05). Moreover, as compared to the control group, sows and newborn piglets in the Na2SeO3 and HMSeBA groups had a lower serum interleukin-6 (p < 0.05) concentration, and placentas in the HMSeBA group had lower IL-1ß, IL-6 and IL-8 gene expression (p < 0.05). In conclusion, maternal supplementation of HMSeBA during pregnancy improved antioxidant capacities and reduced the inflammation level in mater, placenta, and fetus. This finding may highlight the important role of selenoproteins (especially GPXs) in preventing negative consequences of over-production of free radicals and inflammatory cytokines during gestation and at births.

A versatile cholera toxin conjugate for neuronal targeting and tracing.

Tracing of neurons plays an essential role in elucidating neural networks in the brain and spinal cord. Cholera toxin B subunit (CTB) is already widely used as a tracer although its use is limited by the need for immunohistochemical detection. A new construct incorporating non-canonical azido amino acids (azido-CTB) offers a novel way to expand the range and flexibility of this neuronal tracer. Azido-CTB can be detected rapidly in vivo following intramuscular tongue injection by 'click' chemistry, eliminating the need for antibodies. Cadmium selenide/zinc sulfide (CdSe/ZnS) core/shell nanoparticles were attached to azido-CTB by strain-promoted alkyne-azide cycloaddition to make a nano-conjugate. Following tongue injections the complex was detected in vivo in the brainstem by light microscopy and electron microscopy via silver enhancement. This method does not require membrane permeabilization and so ultrastructure is maintained. Azido-CTB offers new possibilities to enhance the utility of CTB as a neuronal tracer and delivery vehicle by modification using 'click' chemistry.

The selenocompound 1-methyl-3-(phenylselanyl)-1H-indole attenuates depression-like behavior, oxidative stress, and neuroinflammation in streptozotocin-treated mice.

Major depressive disorder (MDD) is a chronic mental illness affecting a wide range of people worldwide. The pathophysiology of MDD is not completely elucidated, but it is believed that oxidative stress and neuroinflammation are involved. In light with this, the aim of the present study was to investigate whether a single administration of the antioxidant 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI) was able to reverse the streptozotocin-induced depression-like behavior, oxidative stress, and neuroinflammation in mice. MFSeI (10 mg/kg) was administered intragastrically (i.g.) 24 h after the intracerebroventricular injection of STZ (0.2 mg/4 µL/per mouse). Thirty minutes after MFSeI administration, behavioral tests and neurochemical analyses were performed. Fluoxetine (10 mg/kg, i.g.) was used as a positive control. MFSeI and fluoxetine were able to reverse the STZ-induced depression-like behavior, as evidenced by decreased immobility time in the forced swimming test and increased grooming time in the splash test. Mechanistically, MFSeI reversed the increased levels of reactive species and lipid peroxidation in the prefrontal cortices and hippocampi of STZ-treated mice. Additionally, neuroinflammation (i.e. expression of NF-κB, IL-1ß, and TNF-α) and the reduced mRNA levels of BDNF in the and hippocampi of depressed mice were reversed by treatment with MFSeI. Fluoxetine did not improve the STZ-induced alterations at the levels of reactive species, NF-κB and BDNF in the prefrontal cortices neither the levels of TNF-α in both brain regions. Together, these data suggest that the MFSeI may be a promising compound with antidepressant-like action, reducing oxidative stress and modulating inflammatory pathways in the brain of depressed mice.

Comparison of three oral selenium compounds in cancer patients: Evaluation of differential pharmacodynamic effects in normal and malignant cells.

BACKGROUND: Selenium (Se) compounds have demonstrated therapeutic synergism in combination with anticancer treatments whilst reducing normal tissue toxicities in a range of experimental models. While reduction in some toxicities of chemotherapy and radiation has been confirmed in randomised clinical trials, they have not been powered to evaluate improved anticancer efficacy. A lack of data on the clinical potencies of the main nutritionally-relevant forms of Se and the relationship between their pharmacokinetic (PK) profiles and pharmacodynamic (PD) effects in cancer patients has hampered progress to date. The primary objective of this study was to determine the dose and form of Se that can be most safely and effectively used in clinical trials in combination with anti-cancer therapies. STUDY METHODS: In a phase I randomised double-blinded study, the PD profile of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in two cohorts of 12 patients, one cohort with chronic lymphocytic leukaemia (CLL) and the other with solid malignancies. All 24 patients were randomised to receive 400 µg of elemental Se as either SS, MSC or SLM, taken orally daily for 8 weeks. PD parameters were assessed before, during and 4 weeks after Se compound exposure in plasma and peripheral blood mononuclear cells (PBMCs). RESULTS: No significant sustained changes were observed in plasma concentrations of vascular endothelial growth factor-α (VEGF-α), expression of proteins associated with endoplasmic reticulum stress (the unfolded protein response) or in intracellular total glutathione in PBMCs, in either disease cohort or when grouped by Se compound. CONCLUSIONS: At the 400 µg dose level no substantial changes in PD parameters were noted. Extrapolating from pre-clinical data, the dose examined in this cohort was too low to achieve the Se plasma concentration (≥ 5 µM) expected to elicit significant PD effects. Recruitment of a subsequent cohort at higher doses to exceed this PK threshold is planned.

Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

H2Se Induces Reductive Stress in HepG2 Cells and Activates Cell Autophagy by Regulating the Redox of HMGB1 Protein under Hypoxia.

Rationale: Selenium has been shown to have chemotherapeutic effects against cancer. However, the anti-cancer mechanism of selenium is not fully understood, and the role of hydrogen selenide (H2Se), which is a common metabolite of dietary selenium compounds, has not been elucidated due to the lack of detection methods. In this study, we revealed a new anti-cancer mechanism of selenite with the help of a H2Se fluorescent probe. Methods: HepG2 cells were cultured under a simulated tumor hypoxic microenvironment. The H2Se and H2O2 levels were detected by fluorescent probes in living cells and in mice. Autophagic and apoptotic proteins were detected by Western blotting. The redox of HMGB1 protein were analyzed by non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis. Results: After pharmacological doses of Na2SeO3 treatment of HepG2 cells under hypoxic conditions, high levels of H2Se were produced before cell death. The H2Se accumulation resulted in reductive stress instead of oxidative stress, which was induced by Na2SeO3 treatment under normoxic conditions. Furthermore, H2Se targeted the HMGB1 protein and induced cell autophagy. H2Se could interrupt the disulfide bond in HMGB1 and promote its secretion. The reduced HMGB1 outside the cells stimulated cell autophagy by inhibiting the Akt/mTOR axis. Here, autophagy played a dual role, i.e., mild autophagy inhibited apoptosis, while excessive autophagy led to autophagy-associated cell death. Conclusions: These results show that H2Se plays a key role during HepG2 cell death induced by selenite. Our findings reveal a new anti-cancer mechanism of selenite and provide a new research area for selenium studies.

Antioxidant, gene expression and metabolomics fingerprint analysis of Arabidopsis thaliana treated by foliar spraying of ZnSe quantum dots and their growth inhibition of Agrobacterium tumefaciens.

Nanotechnology, new fascinating field of science, is bringing many application's options. However, it is necessary to understand their potential environmental risk and toxicity. Zinc selenide quantum dots (ZnSe QDs) are getting valuable due to wide industrial usage, mainly as cadmium free diodes or stabilizing ligand. Thanks to unique properties, they could also open the possibilities of application in the agriculture. Their effects on living organisms, including plants, are still unknown. Therefore, the attention of this work was given to antioxidant response of Arabidopsis thaliana to 100 and 250 µM ZnSe QDs foliar feeding. ZnSe QDs treatment had no statistically significant differences in morphology but led to increased antioxidant response in the leaves at the level of gene expression and production secondary antioxidant metabolites. Concurrently, analysis of growth properties of Agrobacterium tumefaciens was done. 250 µM ZnSe solution inhibited the Agrobacterium tumefaciens viability by 60%. This is the first mention about effect ZnSe QDs on the plants. Although QDs induced oxidative stress, the apply treatment dose of ZnSe QDs did not have significant toxic effect on the plants and even no morphological changes were observed. However, the same amount of ZnSe QD induced an inhibitory effect on Agrobacterium tumefaciens.

Histological analysis of rat prostate under exogenous testosterone and low dose of oral selenium administration / Histología de la próstata de ratón influenciada por testosterona y la dosis supranutricional de selenio / Histologia da próstata de rato sob influência de testosterona exógena e dose supranutricional de selênio

Objective: to verify selenium effectiveness in maintenance of prostate tissue architecture. Method: experimental study using 20 adult 90-day-old male rats divided into the following groups: TG, 05 animals that received injectable testosterone; TSG, 05 animals that received injectable testosterone and weekly doses of selenium by gavage; CG1, 05 intact animals; CG2, 05 animals that received saline injection and saline by gavage. Results: characteristic architecture was found in tissue samples from animals of CG with cubic/prismatic secretory epithelium surrounded by fibro-muscular stroma. Animals of TG showed an increase in prostatic epithelium height, increase in the number of blood vessels in stroma and presence of proliferative lesions. Proliferative lesions were also found in tissue samples from animals of TSG, besides having improve in epithelial height, as seen in TG. Conclusion: it is concluded that selenium at this concentration has no effectiveness in modulating morphology of prostatic tissue of adult rats.(AU)

Objetivo: verificar la eficacia del selenio en mantener la morfología tisular. Método: estudio experimental, utilizando 20 ratones machos adultos (5 animales/grupo), divididos en: TG, recibieron testosterona inyectable; TSG, recibieron testosterona inyectable y dosis semanales de selenio por gavado; CG1, animales intactos; CG2, recibieron solución salina inyectable y por gavado. Resultados: una arquitectura característica fue encontrada en las muestras tisulares de los animales del CG, con epitelio cúbico/prismático envuelto por estroma fibro-muscular. En los animales del TG la próstata presentó un epitelio con células más altas, un aparente aumento en el número de vasos sanguíneos estromais, además de la presencia de lesiones proliferativas. También se encontraron lesiones proliferativas en las muestras tisulares de los animales del TSG, además de presentar mayor altura del epitelio, como vistas en TG. Conclusión: se concluye así que el Selenio, en esta concentración, parece no ser eficaz en la protección contra las modificaciones promovidas por la administración de T exógena en ratas adultas.(AU)

Objetivo: verificar a eficácia do selênio na manutenção da morfologia tecidual prostática. Métodos: estudo experimental, utilizando 20 ratos machos adultos, divididos em: TG, 05 animais que receberam testosterona injetável; TSG, 05 animais que receberam testosterona injetável e doses semanais de selênio por gavagem; CG1, 05 animais intactos; CG2, com 05 animais que receberam solução salina injetável e por gavagem. Resultados: uma arquitetura característica foi encontrada nas amostras teciduais dos animais do CG, com epitélio cúbico/prismático envolvido por estroma fibro-muscular. Nos animais do TG a próstata apresentou um epitélio com células mais altas, um aparente aumento no número de vasos sanguíneos no estroma, além da presença de lesões proliferativas. Também foram encontradas lesões proliferativas nas amostras teciduais dos animais do TSG, além de apresentarem maior altura do epitélio, como vistas no TG. Conclusão: conclui-se assim, que o Selênio, nesta concentração, parece não ser eficaz na proteção contra as modificações promovidas pela administração de T exógena em ratos adultos.(AU)

Enhanced bioreduction-responsive diselenide-based dimeric prodrug nanoparticles for triple negative breast cancer therapy.

Efficient drug accumulation in tumor is essential for chemotherapy. We developed redox-responsive diselenide-based high-loading prodrug nanoparticles (NPs) for targeted triple negative breast cancer (TNBC) treatment. Method: Redox-responsive diselenide bond (Se-Se) containing dimeric prodrug (PTXD-Se) was synthesized and co-precipitated with TNBC-targeting amphiphilic copolymers to form ultra-stable NPs (uPA-PTXD NPs). The drug loading capacity and redox-responsive drug release behavior were studied. TNBC targeting effect and anti-tumor effect were also evaluated in vitro and in vivo.Results: On-demand designed paclitaxel dimeric prodrug could co-precipitate with amphiphilic copolymers to form ultra-stable uPA-PTXD NPs with high drug loading capacity. Diselenide bond (Se-Se) in uPA-PTXD NPs could be selectively cleaved by abnormally high reduced potential in tumor microenvironment, releasing prototype drug, thus contributing to improved anti-cancer efficacy. Endowed with TNBC-targeting ligand uPA peptide, uPA-PTXD NPs exhibited reduced systemic toxicity and enhanced drug accumulation in TNBC lesions, thus showed significant anti-tumor efficacy both in vitro and in vivo. Conclusion: The comprehensive advantage of high drug loading, redox-controlled drug release and targeted tumor accumulation suggests uPA-PTXD NPs as a highly promising strategy for effective TNBC treatment.

Synthesis and antidiabetic properties of chitosan-stabilized selenium nanoparticles.

Chitosan-stabilized selenium nanoparticles (CTS-SeNPs) were prepared through the reduction of selenite acid with ascorbic acid. The optimal synthesis conditions of CTS-SeNPs were obtained by orthogonal experiments. Besides, the size, morphology and stability of CTS-SeNPs were characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM) and dynamic light scattering (DLS). The results showed that, the CTS-SeNPs with diameter of about 54 nm could be obtained under the optimal conditions (temperature of 25 °C, reaction time of 2 h, Vc concentration of 0.04 M and the CTS concentration of 1.0 mg/mL). CTS-SeNPs were uniform spherical and could be stable for approximately 60 days at 4 °C. Further, the antidiabetic activities of CTS-SeNPs in streptozotocin (STZ)-induced diabetic mice were investigated as well. The results revealed that CTS-SeNPs at a dose of 2.0 mg Se/kg bw exhibited higher antidiabetic activity than other doses of CTS-SeNPs and other selenium compounds with the same selenium content.

Selenium in Radiation Oncology-15 Years of Experiences in Germany.

Introduction: Se measurement and supplementation in radiation oncology is a controversial issue. The German Working Group Trace Elements and Electrolytes in Oncology (AKTE) has conducted a number of studies on this issue, which are summarized in this review. Strategies have been tested and developed, aiming to stratify the patients with a potential need for supplemental Se and how best to monitor Se supplementation with respect to health effects and risks. Methods: We analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two randomized phase III clinical studies were conducted for testing a potential radioprotective effect of supplemental Se during radiation therapy in patients with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results: A relative Se deficit in whole blood or serum was detected in the majority of tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate cancer). In prostate cancer, tissue Se concentrations were relatively elevated in the carcinoma centre as compared to the surrounding compartment or as compared to tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se supplementation successfully corrected Se-deficiency in the patients analyzed and decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy patients with carcinomas of the uterus. Survival data imply that Se supplementation did not interfere with radiation success. Some positive effects of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy were noted in a second randomized trial in patients with head and neck cancer. We have not observed any adverse effects of supplemental Se in our studies. Conclusions: Se supplementation yielded promising results concerning radioprotection in tumor patients and should be considered as a promising adjuvant treatment option in subjects with a relative Se deficit.

Impact of Selenium Addition to Animal Feeds on Human Selenium Status in Serbia.

Research conducted during the 1980s demonstrated Se deficiency in humans. Increased inclusion of selenium in animal feeds started from the year 2000 onwards. The aim of this study was to estimate the effects of selenium inclusion in animal feeds on human selenium status and dietary habits of the Serbian population related to food of animal origin. Plasma selenium concentration in healthy adult volunteers, including residents of one of the regions with the lowest (Eastern Serbia, n = 60) and of one of the regions with the highest Se serum levels reported in the past (Belgrade, n = 82), was determined by hydride generation atomic absorption spectrometry. Multivariate analysis was employed to determine the correlation between Se plasma levels and dietary intake data derived from food frequency questionnaires and laboratory tests. The mean plasma Se level of the participants was 84.3 ± 15.9 µg/L (range: 47.3-132.1 µg/L), while 46% of participants had plasma Se levels lower than 80 µg/L. Frequency of meat, egg, and fish consumption was significantly correlated with plasma selenium level (r = 0.437, p = 0.000). Selenium addition to animal feed in the quantity of 0.14 mg/kg contributed to the improvement of human plasma selenium levels by approximately 30 µg/L.

Forms of selenium in vitamin-mineral mixes differentially affect serum prolactin concentration and hepatic glutamine synthetase activity of steers grazing endophyte-infected tall fescue.

The goal of this study was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. an 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially affect metabolic parameters and performance of growing steers grazing toxic endophyte-infected tall fescue mixed forage (E+) pasture. Predominately-Angus steers (BW = 183 ± 34 kg) were randomly selected from herds of fall-calving cows grazing E+ pasture and consuming VM mixes that contained 35 ppm Se as ISe, OSe, and MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of an E+ pasture (0.51 ppm total ergovaline per ergovalinine; 10.1 ha). Steers were assigned (n = 8 per treatment) to the same Se-form treatments upon which they were raised. Selenium treatments were administered by daily top-dressing 85 g of VM mix onto 0.23 kg soyhulls, using in-pasture Calan gates. The PROC MIXED procedure of SAS was used to assess effect of Se-form treatments on whole blood Se (ng/mL) and serum prolactin (ng/mL) at day 0, 22, 43, 64, and 86, and caudal arterial area (mm2) at day -7, 43, and 86. The effect of Se treatment on ADG (day 86), and liver glutamine synthetase (GS) mRNA, protein, and activity (nmol/mg wet tissue/min) were assessed using the PROC GLM procedure of SAS. Fisher's protected LSD procedure was used to separate treatment means. Whole blood Se increased (P < 0.01) for all treatments from day 0 to 22 and then did not change (P ≥ 0.17), and was greater (P ≤ 0.04) for MIX and OSe steers. Serum prolactin decreased (P < 0.01) over time and was greater (P < 0.05) for MIX and OSe steers. Liver GS mRNA content was 66% and 59% greater (P < 0.05) in MIX and OSe steers, respectively, than ISe steers. Liver GS protein content in MIX steers was 94% more (P < 0.01) than ISe steers. Moreover, MIX and OSe steers had 99% and 55% more (P ≤ 0.01) liver GS activity, respectively, than ISe steers. ADG was not affected (P = 0.36) by Se treatments. We conclude that consumption of 3 mg Se/d as OSe or MIX forms of Se in VM mixes increased 1) whole blood Se content, an indicator of greater whole-body Se assimilation; 2) serum prolactin, the reduction of which is a hallmark of fescue toxicosis; and 3) hepatic GS activity, indicating greater hepatic assimilation of acinar ammonia. However, 4) these positive effects on metabolic parameters were not accompanied by increased growth performance.

Seleno-compounds and Carnosic Acid Added to Diets with Rapeseed and Fish Oils Affect Concentrations of Selected Elements and Chemical Composition in the Liver, Heart and Muscles of Lambs.

The objective of our studies was to investigate effects of carnosic acid (CA), selenized yeast (SeY) and selenate (SeVI) added to the diet including rapeseed oil (RO) and fish oil (FO) on concentrations of elements, fatty acids (FAs), tocopherols, cholesterol, and malondialdehyde in the liver, heart, musculus longissimus dorsi (MLD), and musculus biceps femoris (MBF) of lambs. Lambs were fed diets: group I-the basal diet (BD) with RO; group II-BD with RO and FO; group III-BD with RO, FO, and CA; group IV-BD with RO, FO, CA, and SeY; group V-BD with RO, FO, CA, and SeVI. The diets with Se compounds increased Se concentrations in all tissues compared with other diets. The diet with SeVI increased Cd, Sb, and Pb concentrations in the liver compared to groups I, II, and IV. The diets containing Se compounds increased Sb and Pb concentrations in MBF compared to groups I and II. All diets with CA reduced As, Sb, and Pb concentrations in MLD compared to groups I and II. All diets with FO increased concentrations of FAs and malondialdehyde in the liver compared to group I. All diets with FO decreased FAs concentrations in MBF compared to group I. The diets containing CA with/without Se compounds increased malondialdehyde concentrations in MBF compared to groups I and II. The diet with Se compounds reduced malondialdehyde concentrations in MLD compared to group II. All diets with FO changed concentrations of tocopherols and cholesterol in all tissues compared to group I. Our study showed that the addition of SeY or SeVI to the experimental diet increased the concentration of Se in all assayed tissues of lambs without adversely influencing performance or causing physiological disorders in internal organs. Both, SeY or SeVI added to the experimental diet decreased the oxidative stress and the concentrations of As, Sb, and Pb in MLD compared with the diets containing RO, irrespective of the presence of FO (groups I and II). Our study provides useful knowledge for nutritionists carrying out further investigations aimed at improving farm animal health, performance, and the nutritional quality of animal products for humans.

Safety Assessment and Comparison of Sodium Selenite and Bioselenium Obtained from Yeast in Mice.

Detailed safety assessment of sodium selenite and bioselenium (bio-Se) was conducted and the results were compared and discussed for the purpose of assessing safety of bio-Se for use in food applications. In this work, acute toxicity studies, micronucleus test, and sperm aberration study in mice, 30-day feeding test of mice, were conducted to evaluate the toxicity of bio-Se obtained from yeast with different fermentation time (transformative time: one month, three months, and six months), and the results were compared with that of inorganic Se (sodium selenite). LD50 of sodium selenite was calculated to be 21.17 mg/kg. LD50 of bio-Se obtained from yeast with different fermentation time was calculated to be 740.2 mg/kg, 915.3 mg/kg, and 1179.0 mg/kg, respectively. In the genotoxicity test, bio-Se did not show cytotoxicity and genotoxicity of mice while sodium selenite at all dose groups was significantly different from the negative group. In the 30-day subchronic oral toxicity study, sodium selenite may slow down the growth of the mice and lead to organic damage to some extent. Bio-Se had facilitated effect towards the body weight of the mice and had no significant effect on the shape and function of the important organs of the mice.

Hydroxy-selenomethionine: A novel organic selenium source that improves antioxidant status and selenium concentrations in milk and plasma of mid-lactation dairy cows.

This study aimed to evaluate the effect of hydroxy-selenomethionine (HMSeBA), a novel organic selenium (Se) source, on milk performance, antioxidative status, and Se concentrations in the milk and plasma of mid-lactation dairy cows compared with that of sodium selenite (SS). Fifty mid-lactation dairy cows with similar days in milk, milk yield, and parity received the same basal diet containing 0.06 mg of Se/kg of DM. They were assigned to 1 of 5 treatments according to a randomized complete block design: negative control (without Se supplementation), SS supplementation (0.3 mg of Se/kg of DM; SS-0.3) or HMSeBA supplementation (0.1, 0.3, or 0.5 mg of Se/kg of DM: SO-0.1, SO-0.3, and SO-0.5, respectively). The experiment lasted for 10 wk, including a pretrial period of 2 wk. The results indicated that neither Se supplementation nor Se source affected dry matter intake, milk yield, milk composition, or blood biochemical parameters, except for milk fat percentage. Simultaneously, milk fat percentage and milk fat yield increased linearly as the quantity of HMSeBA supplementation was increased. Production of 4% FCM and ECM was elevated linearly as dietary HMSeBA increased. The SO-0.3 group showed higher serum activity of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase than the SS-0.3 group, but malondialdehyde content was not affected by Se source. Furthermore, HMSeBA supplementation linearly increased the activities of serum glutathione peroxidase and superoxide dismutase, but decreased malondialdehyde content. Compared with the SS-0.3 group, the SO-0.3 group showed augmented concentrations of total Se in milk and plasma, and total Se milk-to-plasma concentration ratio. In addition, increasing doses of HMSeBA linearly increased the concentrations of total Se in the milk and plasma. This study demonstrates that HMSeBA improves antioxidant status and increases milk and plasma Se concentrations more effectively than SS, indicating that HMSeBA could replace SS as an effective organic Se source for lactating dairy cows.

Synergistic Effects of SAM and Selenium Compounds on Proliferation, Migration and Adhesion of HeLa Cells.

BACKGROUND/AIM: To determine the antitumor activities and molecular mechanism of selenium compounds in HeLa cells. MATERIALS AND METHODS: Western blotting was used to detect ERK and AKT activation in HeLa cells induced by selenium compounds selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the antitumor effects of SAM and selenium compounds were evaluated in HeLa cells. RESULTS: MeSeA inhibited ERK and AKT signaling pathways and suppressed the proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM led to a statistically significant inhibition of proliferation, migration and adhesion of HeLa cells. CONCLUSION: MeSeA, MeSeCys and SeMet exert different antitumor activities by inhibiting ERK and AKT signaling pathways. The combination of MeSeA and SAM exhibited better antitumor effects compared to the other treatments.