The Pharmacology and Therapeutic Utility of Sodium Hydroselenide.

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe-/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.

Selenium nanoparticles inhibit the formation of atherosclerosis in apolipoprotein E deficient mice by alleviating hyperlipidemia and oxidative stress.

Atherosclerosis can cause severe cardiovascular diseases, which is the most common cause of death in the world. It's of great significance to study the prevention and treatment of atherosclerosis. Selenium nanoparticles (SeNPs) has drawn more and more attention due to high biological activity, high bioavailability, strong antioxidant capacity and low toxicity, exhibiting great potential in biomedical application. Thus, this study aimed at explore the anti-atherosclerotic effect of two kinds of SeNPs, bovine serum albumin (BSA) surface-decorated SeNPs and chitosan (CS) surface-decorated SeNPs (CS-SeNPs), in apolipoprotein E deficient (ApoE-/-) mice fed with a high-cholesterol and high-fat diet, and the possible mechanisms. The results demonstrated that both BSA-SeNPs (25, 50 and 100 µg Se/kg body weight/day) and CS-SeNPs (50 µg Se/kg body weight/day) could reduce atherosclerotic lesions in ApoE-/- mice after oral administration for 12 weeks. And these effects might mainly attributed to the ability of BSA-SeNPs and CS-SeNPs to inhibit hyperlipidemia by suppressing hepatic cholesterol and fatty acid metabolism, and alleviate oxidative stress by enhancing antioxidant activity. Moreover, the benefits of BSA-SeNPs were dose-dependent and the medium dose of BSA-SeNPs (50 µg Se/kg body weight/day) was optimal. Generally, BSA-SeNPs with mean size 38.5 nm and negative surface charge showed better anti-atherosclerotic effect than CS-SeNPs with mean size 65.8 nm and positive surface charge. These results suggested that SeNPs could significantly alleviate the formation of atherosclerosis in ApoE-/- mice, possibly by inhibiting hyperlipidemia and oxidative stress, exhibiting a potential to serve as an anti-atherosclerotic agent.

Effect of boiling and frying on the selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato (Solanum tuberosum L.).

Selenium-enriched potato is a good supplement for selenium-deficient populations. This study evaluated the influence of two most common cooking methods, including boiling and frying, on selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato tubers. After foliar application of 200 µg/mL sodium selenite, potato tubers with 1.33 µg Se/g were obtained. Peeling resulted in 53.4%-69.9% loss of selenium in tubers. The total selenium content decreased by approximately 43.3% after boiling, among which up to 38.5% of the lost selenium is found in the boiling water. Nearly 31.7% of selenium was lost via volatilization during frying. Both cooking methods significantly enhanced the bioaccessibility of Se(IV) in tubers. Whereas SeMeCys became less bioaccessible after boiling. SeMet and SeCys2 in fired tubers were not accessible after digestion. This study suggested that boiling is more appropriate for cooking selenium-enriched potatoes.

Development of Formulation Methods and Physical Characterization of Injectable Sodium Selenite Nanoparticles for the Delivery of Sorafenib tosylate.

BACKGROUND: Sorafenib is the first oral therapeutic agent to show the activity against human hepatocellular carcinoma. Sorafenib leads to severe toxicity due to the multiple-dose regimen. Reducing the overall dose of sorafenib through injectable dosage form to release sustainably is of therapeutically more important to combat drug-induced toxicity. OBJECTIVE: The purpose of this study was to formulate and evaluate the physical parameters of sorafenib- loaded Sodium Selenite Nanoparticles (SSSNP). METHODS: Two different methods: chemical crosslinking and solvent evaporation were applied for the formulation of nanoparticles using various crosslinkers such as formaldehyde, magnesium sulfate, tripolyphosphate, dextran sulfate, and aluminum hydroxide. Physical characterization was performed with zeta potential analysis, polydispersity index, particle size and scanning electron microscopic studies for morphological analysis for all the formulated nanoparticles developed using the chemical crosslinking technique based ionic interaction. RESULTS: Tripolyphosphate was selected as an ideal crosslinker and used for nanoparticle formulation with the solvent evaporation technique. Based on the physical characterization, SSSNP was formulated successfully with the solvent evaporation technique using tripolyphosphate as a cross-linker. The zeta potential of SSSNP was -37.5 mV, PDI was approximately 0.3 to 0.4, and the observed size (diameter) was in the range of 208 nm to 0.2 µm. Furthermore, the particles were smooth in morphology and appeared as crystals. CONCLUSION: The novel injectable sorafenib loaded sodium selenite nanoparticle dosage form will serve better than conventional oral dosage form to elicit a safe therapeutic effect.

Effects of selenium combined with zinc amendment on zinc fractions and bioavailability in calcareous soil.

Selenium (Se) and zinc (Zn) are two important trace elements for human being and animals. The interaction between Se and Zn on the bioavailability of Zn in soil is still unclear. Therefore, pot experiments exposed to different dosages of zinc sulfate (ZnSO4) (0, 20, and 50 mg/kg soil) and sodium selenite (Na2SeO3) (0, 0.5, 1.0, and 2.5 mg/kg soil) were conducted to investigate the effects of selenite application on Zn bioavailability in calcareous soil and its related mechanisms. The total Zn content of different tissues (roots and shoots) of pak choi (Brassica chinensis L.) and the changes in Zn fraction distribution in soil before planting and after harvest were determined, and the mobility factor (MF) and distribution index (DI) of Zn in soils were calculated. In addition, the Pearson correlation and path analysis were conducted to clarify the relationships between Zn fractions in soil and the Zn uptake of pak choi. Results showed that Se amendment elevated soil Zn bioavailability at appropriate levels of Se and Zn. When 1.0 and 2.5 mg/kg of Se and 20 mg/kg of Zn were applied in soil, the proportion of exchangeable Zn (Ex-Zn) and Zn weakly bound to organic matter (Wbo-Zn) to the total content of Zn was significantly increased by 28.14%-82.52% compared with that of the corresponding single Zn treatment. Therefore, the Zn concentration in the shoots of pak choi was significantly increased by 27.2%-31.1%. High Zn (50 mg/kg) and Se co-amended treatments showed no significantly beneficial effect on the bioavailability of Zn. In addition, the potential available Zn content in soil (weakly bound to organic matter and carbonate bound Zn) and MF and DI values were all positively correlated with the Zn concentrations in pak choi, indicating that these indexes can be used to predict the bioavailability of Zn in soil. This study can provide a good reference for Se and Zn biofortification of plants in calcareous soil.

Physicochemical properties and bioactivities of original and Se-enriched polysaccharides with different molecular weights extracted from Pleurotus ostreatus.

Three polysaccharides (WZP1, WZP2, WZP3) and their Se-enriched products (SeWZP1, SeWZP2 and SeWZP3) were obtained from Pleurotus ostreatus using a simple, rapid method and HNO3-Na2SeO3 method, respectively. The molecular weight distribution profiles of all samples except SeWZP2 showed double peaks. The average molecular weights (Mw) of WZP1-3 were 48.6 kDa, 20.2 kDa and 11.8 kDa, respectively, and of SeWZP1-3 were 19.6 kDa, 37.7 kDa, 14.5 kDa, respectively. The complexity of monosaccharide composition of WZP1-3 was inversely proportional to the ethanol concentration used in the ethanol precipitation process. Additionally, the results of biological activity tests indicated that α-glucosidase inhibitory activity of WZP1-3 was related to the molecular weight and the monosaccharide composition complexity. The selenized modification can improve the α-glucosidase-inhibiting, hydroxyl radical-scavenging activity of P. ostreatus polysaccharides. Therefore, by improving their bioactivities by selenization, the polysaccharides of P. ostreatus could be utilized as a natural health food supplement.

Forms of selenium in vitamin-mineral mixes differentially affect serum alkaline phosphatase activity, and serum albumin and blood urea nitrogen concentrations, 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. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral mix would differentially affect serological and hepatic parameters of growing steers grazing toxic endophyte-infected tall fescue-mixed forage pasture. Predominately Angus steers (BW = 183 ± 34 kg) were randomly selected from herds of fall-calving cows grazing endophyte-infected tall fescue-mixed pasture and consuming vitamin-mineral 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 endophyte-infected tall fescue-mixed pasture (0.51 ppm total ergovaline + ergovalinine; 10.1 ha). Steers were assigned (n = 8 per treatment) to the same Se form treatments upon which they were raised. Se treatments were administered by daily top-dressing 85 g of vitamin-mineral mix onto 0.23 kg soyhulls, using in-pasture Calan gates. The PROC MIXED procedure of SAS was used to assess the effect of Se form treatments on serum parameters at day 0, 22, 43, 64, and 86. After slaughter, the effect of Se treatment on hepatic alkaline phosphatase (tissue nonspecific isoform, TNALP) mRNA, protein, and albumin protein content was assessed using the PROC GLM procedure of SAS. Fisher's protected LSD procedure was used to separate treatment means. Partial correlation analysis was used to evaluate the relationship among whole blood Se concentration and serum parameters, accounting for the effect of time. Across periods, MIX steers had more (P ≤ 0.04) serum albumin than OSe and ISe steers, respectively. However, the relative hepatic bovine serum albumin protein content was not affected (P = 0.28) by Se treatments. Serum alkaline phosphatase activity was greater (P ≤ 0.01) in MIX and OSe steers. Similarly, hepatic TNALP protein content in MIX steers was greater (P = 0.01) than ISe steers. Partial correlation analysis revealed that serum albumin, blood urea nitrogen, and alkaline phosphatase activity were correlated (r ≥ 0.23, P ≤ 0.02) with whole blood Se concentration. In summary, consumption of 3 mg Se/d as OSe or MIX forms of Se in vitamin-mineral mixes increased serum albumin concentration and alkaline phosphatase activity, the reduction of which is associated with fescue toxicosis. We conclude that the organic forms of Se ameliorated the depression of 2 of known serological biomarkers of fescue toxicosis.

Selenium attenuates apoptosis and p-AMPK expressions in fluoride-induced NRK-52E cells.

Fluoride is widely distributed in the environment, and excessive fluoride intake can induce cytotoxicity, DNA damage, and cell cycle changes in many tissues and organs, including the kidney. Accumulating evidence demonstrates that selenium (Se) administration ameliorates sodium fluoride (NaF)-induced kidney damage. However, the potentially beneficial effects of Se against NaF-induced cytotoxicity of the kidney and the underlying molecular mechanisms of this protection are not fully understood. At present, in this study, the normal rat kidney cell (NRK-52E) was used to investigate the potentially protective mechanism of Se against NaF-induced apoptosis, by using the methods of pathology, colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blot. The experiment was designed with a control group, two NaF-treated groups (NaF, 5, 20 mg/L), two sodium selenite-treated groups (Na2SeO3, 17.1, 34.2 µg/L), and four Se + NaF-treated groups (Na2SeO3, 17.1, 34.2 µg/L; NaF, 5, 20 mg/L). The results indicate that selenium can attenuate apoptosis and AMPK phosphorylation in the NRK-52E cell induced with fluoride. These results imply that selenium is capable to modulate fluoride-induced NRK-52E cell apoptosis via regulating the expression levels of the proteins involved in mitochondrial pathway and changes in p-AMPK expressions may also be a key process in preventing fluorosis.

Extracellular Synthesis of Selenium Nanoparticles from an Actinomycetes Streptomyces griseoruber and Evaluation of its Cytotoxicity on HT-29 Cell Line.

BACKGROUND: Selenium nanoparticles (SeNPs) have gained significant importance because of its bioavailability, least toxicity, its interaction with proteins and its biocompatibility. OBJECTIVE: In the present study, the extracellular synthesis of SeNPs was carried out by using culture supernatant of Streptomyces griseoruber, an Actinomycetes member isolated from the soil and cytotoxicity was tested on HT-29 cell line. METHODS: Culture supernatant was mixed with 1mM sodium selenite for the biosynthesis of SeNPs. Characterisation of the synthesised SeNPs was done by UV-Visible spectrophotometer, FTIR, XRD, DLS and HR-TEM. The cytotoxicity of nanoparticles on HT-29 cell line was studied by MTT assay and with different staining procedure. RESULTS: Bioreduction of SeNPs was confirmed by UV-Visible spectrophotometer that showed the peak at 575 nm. Size and distribution of the biosynthesised SeNPs were analysed by HR-TEM that showed the formation of particle size in the range of 100-250nm. The synthesised SeNPs showed good cytotoxic activity against HT-29 cell line with 40.5%, 33% and 23.7% of cell viability at 2µg/ ml, 4µg/ml and 30µg/ml concentration respectively. CONCLUSION: The present study reports the simple and eco-friendly synthesis of SeNPs that showed good cytotoxic activity against HT-29 cell line suggesting that biogenic SeNPs could be a potential chemotherapeutic agent.

Fabrication and stabilization of biocompatible selenium nanoparticles by carboxylic curdlans with various molecular properties.

In this study, carboxylic curdlans (Cur-4, Cur-8, and Cur-24) with different molecular properties and chain conformations were used as stabilizer and capping agent to fabricate stable and water-dispersible selenium nanoparticles (SeNPs). Results showed that molecular properties and chain conformations of carboxylic curdlans remarkably influenced the size, morphology, structure, and stability of SeNPs and the carboxylic curdlan was ligated to SeNPs via OH⋯Se interaction. The as-prepared SeNPs was amorphous and showed homogeneous and monodisperse spherical structure with size of ∼50-90nm. The Cur-8-decorated SeNPs (SeNPs@Cur-8) exhibited smaller particle size (∼56nm) and greater stability than those of the others. The carboxylic curdlan-stabilized SeNPs exhibited excellent antioxidant capacities compared to the control SeNPs. Specifically, SeNPs@Cur-8 with smaller particle size possessed strong antioxidant efficacy. SeNPs@Cur-8 also exhibited low cytotoxic activity against SPCA-1 and HeLa cell lines in vitro.

Green synthesis of selenium nanoparticles using Acinetobacter sp. SW30: optimization, characterization and its anticancer activity in breast cancer cells.

The aim of this study was to synthesize selenium nanoparticles (SeNPs) using cell suspension and total cell protein of Acinetobacter sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of Acinetobacter sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7) and noncancer cells (NIH/3T3, HEK293) were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×109 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na2SeO3 concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of Acinetobacter sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by Acinetobacter sp. SW30 (BSeNPs), but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents.

Synergism between thioredoxin reductase inhibitor ethaselen and sodium selenite in inhibiting proliferation and inducing death of human non-small cell lung cancer cells.

New effective treatment for human non-small cell lung cancer (NSCLC) is needed. The thioredoxin (Trx) system composes of thioredoxin reductase (TrxR), Trx and NADPH. In this study, we combined an organic selenium compound--TrxR inhibitor ethaselen (BBSKE) with low dosage sodium selenite to inhibit proliferation and induce death of NSCLC cells, and identified underlying mechanisms. Synergistic anti-proliferation effect of BBSKE and selenite was found in human NSCLC cell lines, A549, NCI-H1299 and NCI-1266. A significant increase of apoptosis, necrosis and autophagy were observed in the group of BBSKE plus selenite in A549 cells. The autophagy induced by BBSKE and selenite inhibited apoptosis and necrosis. In addition, BBSKE plus selenite induced G2/M arrest, which was verified by the alteration of gene and protein expression of cell cycle regulatory complexes. The intracellular enzyme activity of TrxR was remarkably decreased by cotreatment of BBSKE and selenite. Besides, the mRNA and protein level of TrxR1 and Trx1 were significantly inhibited by cotreatment of BBSKE and selenite. HEK 293 cells overexpressing TrxR1 were more sensitive to BBSKE plus selenite. The nuclear translocation of Trx1 and Ref-1, as well as expression of Ref-1 and AP-1 were inhibited by combination treatment. In short, BBSKE synergizes selenite in inhibiting proliferation and inducing death of NSCLC cells; BBSKE combined with selenite may be a treatment strategy for NSCLC.

Aerobic biogenesis of selenium nanoparticles by Enterobacter cloacae Z0206 as a consequence of fumarate reductase mediated selenite reduction.

In the present study, we examined the ability of Enterobacter cloacae Z0206 to reduce toxic sodium selenite and mechanism of this process. E. cloacae Z0206 was found to completely reduce up to 10 mM selenite to elemental selenium (Se°) and form selenium nanoparticles (SeNPs) under aerobic conditions. The selenite reducing effector of E. cloacae Z0206 cell was to be a membrane-localized enzyme. iTRAQ proteomic analysis revealed that selenite induced a significant increase in the expression of fumarate reductase. Furthermore, the addition of fumarate to the broth and knockout of fumarate reductase (frd) both significantly decreased the selenite reduction rate, which revealed a previously unrecognized role of E. cloacae Z0206 fumarate reductase in selenite reduction. In contrast, glutathione-mediated Painter-type reactions were not the main pathway of selenite reducing. In conclusion, E. cloacae Z0206 effectively reduced selenite to Se° using fumarate reductase and formed SeNPs; this capability may be employed to develop a bioreactor for treating Se pollution and for the biosynthesis of SeNPs in the future.

In vitro study on antagonism mechanism of glutathione, sodium selenite and mercuric chloride.

It has been broadly recognized that the antagonism between selenium (Se) and mercury (Hg) can reduce the toxicity of mercury in organism. Glutathione (GSH) can participate in the metabolism of Se and Hg in vivo and promote the formation of low-toxic Hg-Se complexes, which is a vital way of detoxification for Hg. In this paper, the reaction mechanism of GSH-Se(IV) binary system, GSH-Hg(II) binary system and GSH-Se(IV)-Hg(II) ternary system were systematically studied from the aspects of stoichiometry, thermodynamics and kinetics, via hyphenated techniques including high performance liquid chromatography (HPLC)-ultraviolet (UV) detection, HPLC-inductively coupled plasma mass spectrometry (ICP-MS) and HPLC-electrospray ionization mass spectrometry (ESI-MS). For GSH-Se(IV) binary system, selenodiglutathione (GSSeSG) was the crucial intermediate; the reaction was exothermic and irreversible at constant pressure; it followed second-order kinetics with a fast kinetics (rate constant (k)=4534.2mol-1Ls-1). For GSH-Se(IV)-Hg(II) ternary system, GSSeSeSG would form by the extremely weak dissociation of two molecules of GSSeSG; Hg(II) would rapidly coordinate with GSSeSeSG to generate (HgxSey)n(GS)m precipitates. The mechanism of GSH-Se(IV)-Hg(II) antagonism system involves two processes, the competitive combination of Hg and Se with GSH and the formation of (HgxSey)n(GS)m complexes.

Effects of selenium biofortification of hayfields on measures of selenium status in cows and calves consuming these forages.

Two experiments were conducted to evaluate the Se status of weaned calves (Exp. 1) and pregnant cows and newborn calves (Exp. 2) consuming bermudagrass [ (L.) Pers.] fertilized with Se. Sodium selenate was dissolved into water (8.8 g/L) and sprayed onto hayfields. Selenium-fertilized forage had greater ( ≤ 0.001) Se concentration compared with the control forage without Se fertilization (7.7 ± 1.81 vs. 0.1 ± 0.04 mg Se/kg DM and 10.8 vs. 0.1 mg Se/kg DM for Exp. 1 and Exp. 2, respectively). In Exp. 1, beef calves ( = 32; 176 ± 8.7 kg initial BW) were stratified by BW and randomly assigned to pens (16 pens; 2 calves/pen). Treatments were randomly assigned to pens, including control (no supplemental Se), Se hay, or sodium selenite ( = 2, 7, and 7 pens, respectively). A 42-d pair-feeding design was used, wherein each pen receiving Se hay was paired to a pen receiving sodium selenite. Blood and liver samples were collected on d 0, 21, and 42. Liver Se concentrations were greatest ( ≤ 0.005) on d 42 for calves provided Se hay compared with calves provided sodium selenite or control. This difference was attributed only to paired-feeding groups consuming <3 mg Se daily. In Exp. 2, mature, late-pregnancy cows were randomly assigned to 3 treatments: Se hay ( = 12), sodium selenite ( = 9), or control (no supplemental Se; = 6). Cows assigned to the sodium selenite and Se hay treatments were provided 2.5 mg of supplemental Se daily. Upon enrollment, cows were moved into individual feeding areas at an estimated 30 d prior to calving. Following calving, cotyledon and colostrum samples were collected from cows. Four days later, liver and blood samples were collected from both cows and calves. Selenium-supplemented cows had greater ( ≤ 0.001) liver, cotyledon, plasma, and whole blood Se concentrations compared with cows not receiving supplemental Se. Furthermore, cows provided Se hay tended ( = 0.11) to have greater liver Se concentrations compared with cows provided sodium selenite. Calves born to Se-supplemented cows had greater ( = 0.001) plasma Se concentrations than calves born to cows receiving no supplemental Se. Furthermore, calves born to cows provided Se hay tended ( = 0.06) to have greater plasma Se concentrations compared with calves born to cows provided sodium selenite. These data imply that Se biofortification of hayfields is an effective method to increase Se concentration of forage. Consumption of these forages result in increased Se status of weaned calves, periparturient cows, and their calves.

Sodium Selenite as an Anticancer Agent.

Selenium (Se) is a ubiquitous, albeit not uniformly distributed metalloid present in earth crust. Consequently, its human intake with food products, particularly grains and vegetables, is also very uneven, and in certain cases can result in a severe Se deficiency. It was also documented that Se deficiency observed in some countries and/or geographic regions (e.g. Keshan region in China), is associated with an increased morbidity and mortality of neoplastic diseases. To correct this problem a number of organic and inorganic selenium compounds were developed and tested. However, it is now firmly established that only an inorganic sodium selenite with four-valent Se, and not that with six-valent (selenate) cation shows anticancer activity. This difference in their biological activities is due to their physicochemical properties. Thus selenite (Se+4) can undergo redox reaction, for example with protein's sulfhydryl groups expressed on the surface of tumor cells. In this way selenite prevents non-enzymatic formation of parafibrin that coats tumors cells and hence presents them as 'self' to the innate cellular immune system. Consequently, macrophages of the lymphatic system do not recognize neoplastic cells as 'foreign' bodies and spare them from the immune destruction. This mechanism can explain the failure of various immunotherapies to completely eliminate tumors from human bodies. Another contributing factor to carcinogenesis is the excessive consumption of red meat containing redox-active iron (Fe+3) that initiates parafibrin formation from blood fibrinogen. In conclusion, sodium selenite is a readily available and inexpensive drug of choice in the cancer treatment and prevention.

Supplementation of organic and inorganic selenium to late gestation and early lactation beef cows effect on cow and preweaning calf performance.

Angus × Simmental cows ( = 48; BW = 595 ± 17.4 kg, BCS = 5.26 ± 0.05, and age = 2.3 ± 0.07 yr), pregnant with male fetuses, were used to determine the effect of Se source during the last 80 d of gestation and first 108 d of lactation on cow and calf performance. At 203 d in gestation, cows were blocked by BW, breed composition, age, and calf sire and randomly allotted to organic Se, inorganic Se, or no Se treatments. Diets contained corn silage, corn stover, haylage, dried distillers' grains with solubles, and minerals and were formulated to contain 10.4% CP and 0.90 Mcal/kg NEg during gestation and 12.1% CP and 1.01 Mcal/kg NEg during lactation. Diets were fed daily as a total mixed ration and none, 3 mg/d Se as sodium selenite, or 3 mg/d Se as Sel-Plex were top-dressed daily. At 68 d postpartum (DPP), milk production was calculated using the weigh-suckle-weigh procedure and a milk sample was collected to determine composition. At 108 DPP, cow-calf pairs were commingled until weaning at 210 DPP. Cow BW and BCS ( ≥ 0.56) did not differ between treatments at any time point during the study. Milk production, milk fat, and total solids ( ≥ 0.38) did not differ among treatments. Milk protein tended to increase in cows fed inorganic Se compared with cows fed organic Se ( = 0.07) and milk lactose tended to be greatest in cows fed organic Se ( = 0.10). Conception to AI and overall pregnancy rates did not differ between treatments ( ≥ 0.39). Calf weights and ADG did not differ through 108 DPP ( ≥ 0.77) or for the preweaning period ( ≥ 0.33). Plasma Se concentration was adequate for all cows and did not differ among treatments for cows ( ≥ 0.37) or calves ( ≥ 0.90). Liver Se concentrations in cows fed inorganic or organic Se were greater than in control cows ( < 0.01). Longissimus muscles biopsies taken from progeny at 108 DPP also did not differ between treatments ( = 0.45). In conclusion, dietary Se source did not affect cow performance, milk production, or reproductive efficiency. Organic Se decreased milk protein and increased milk lactose but did not alter preweaning performance of progeny from Se-adequate cows.

Selenylation modification can enhance immune-enhancing activity of Chuanminshen violaceum polysaccharide.

Chuanminshen violaceum polysaccharides (CVPS) were extracted, purified and selenizingly modified. The modification has been achieved by using the HNO3- Na2SeO3 method, and selenizing Chuanminshen violaceum polysaccharides (sCVPS) were evaluated for their physicochemical properties and their potential as adjuvant to modulate cellular and humoral immune responses to hepatitis B subunit vaccine in a mouse model. Our results demonstrated that sCVPS significantly promoted splenocytes proliferation and the production of IL-4 and IFN-γ in vitro. In vivo experiments showed that sCVPS significantly increased the rHBsAg-specific IgG level, IgG subclass (IgG1, IgG2a, and IgG2b) antibody titers, T cells proliferation, levels of IL-4, IL-2, and IFN-γ in CD4 (+)T cells and the level of IFN-γ in CD8(+)T cells. Furthermore, sCVPS increased the activity of natural killer cells and cytotoxic T lymphocytes, thus increasing both cellular and humoral immune responses in vivo. The present data suggest that selenylation of CVPS can significantly improve their immune-enhancing activity both in vitro and in vivo, thus representing a powerful adjuvant for vaccine design.

Sodium selenite and cancer related lymphedema: Biological and pharmacological effects.

A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short-term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti-inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression.

The Selenylation Modification of Epimedium Polysaccharide and Isatis Root Polysaccharide and the Immune-enhancing Activity Comparison of Their Modifiers.

Epimedium polysaccharide (EPS) and isatis root polysaccharide (IRPS) were extracted, purified, and selenizingly modified by nitric acid-sodium selenite method to obtain nine selenizing EPSs (sEPSs), sEPS1-sEPS9 and nine selenizing IRPSs (sIRPSs), sIRPS1-sIRPS9, respectively. Their effects on chicken peripheral lymphocyte proliferation in vitro were compared by MTT assay. The results showed that selenium polysaccharides at appropriate concentration could promote lymphocyte proliferation more significantly than unmodified polysaccharides, sEPS5 and sIRPS5 with stronger actions were picked out and injected into the chickens vaccinated with Newcastle disease vaccine in vivo tests. The peripheral lymphocyte proliferation and serum antibody titer were determined. The results showed that sEPS5 and sIRPS5 could elevate serum antibody titer and promote lymphocyte proliferation more significantly than unmodified polysaccharides, sEPS5 possessed the strongest efficacy. These results indicate that selenylation modification can significantly enhance the immune-enhancing activity of EPS and IRPS, and sEPS5 can be as a new-type immunopotentiator of chickens.