Beneficial antioxidant status of piglets from sows fed selenomethionine compared with piglets from sows fed sodium selenite

BackgroundStudies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and – levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period.MethodsPiglets were monitored from birth to 38 days of age (d). The mother sows’ diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows’ diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet.ResultsFrom 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period.ConclusionsMaternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring’s performance.     

Reduction of selenium-binding protein 1 sensitizes cancer cells to selenite via elevating extracellular glutathione: A novel mechanism of cancer-specific cytotoxicity of selenite

Selenium is an essential trace element and has been extensively studied for preventive effects on cancers. Recent emerging evidence has also shown that selenium at supranutritional dosage has a preferential cytotoxicity in cancer cells and chemotherapeutic drug-resistant cells, but the underlying mechanisms remain largely unknown. This study was to investigate the roles of two distinct representatives of selenium-containing proteins, selenium-binding protein 1 (SBP1) and glutathione peroxidase 1 (GPX1), in selenite-mediated cancer-specific cytotoxicity. We found that there was a significantly inverse correlation between SBP1 and GPX1 protein level in human breast cancers and adjacent matched nontumor tissues (Pearson r=–0.4347, P=0.0338). Ectopic expression of GPX1 enhanced selenite cytotoxicity through down-regulation of SBP1, and SBP1 was likely to be a crucial determinant for selenite-mediated cytotoxicity. Reduction of SBP1 in cancer cells and epirubicin-resistant cells on selenite exposure resulted in a dramatic increase in the generation of hydrogen peroxide and superoxide anion, which in turn caused oxidative stress and triggered apoptosis. Furthermore, knockdown SBP1 by small interfering RNA increased selenite sensitivity by elevating extracellular glutathione (GSH), which spontaneously reacted with selenite and led to the rapid depletion of selenium (IV) in growth medium and the high-affinity uptake of selenite. In conclusion, these findings would improve our understanding of the roles of selenium-containing proteins in selenite-mediated cytotoxicity, and revealed a potent mechanism of the selective cytotoxicity of selenite in cancer cells and drug-resistant cells, in which SBP1 was likely to play an important role in modulating the extracellular microenvironment by regulating the levels of extracellular GSH.     

Selenium nanovirus and its cytotoxicity in selenite-exposed higher living organisms

Selenium (Se) is an essential micronutrient in living organisms, having a narrow margin between essential and potentially toxic intake/exposure. Thus, the biochemistry of Se in living organisms must be studied in-depth to determine the underlying mechanism of Se cytotoxicity. In this study, we report the emergence of selenium nanovirus (SeNVs) in selenite-exposed fish (freshwater and saltwater) and plants (dryland) and its toxicity in them. SeNVs were found in both the abdomen and tail of Oryzias melastigma and saltwater Rhodeus ocellatus, which led to their death. The occurrence of the intracellular assembly of SeNVs was observed in the roots and leaves of corn Zea mays, but not in those of Limnobium laevigatum. SeNVs led to the death of Z. mays but caused chronic toxicity in L. laevigatum. SeNVs should be a system or structure that dissipates the intracellular redox gradients of the host cells, with simple information consisting Se–O, Se–N, or Se–S bond, that would ensure elemental Se ligand binding with nearly specific biomolecules in host cells, thereby maintaining their composition and stabilizing their structure. The multiple toxic effects of Se, therefore, could be the consequence of increase of entropy in the host cells caused by the intracellular assembly of SeNVs. This study may provide an insight into the underlying mechanism of Se in environmental toxicology and its applications in human health.     

The protective role of selenium in recalcitrant Acer saccharium L. seeds subjected to desiccation

Freshly harvested silver maple (Acer saccharinum L.) seeds were soaked in either sodium selenite (10 mg/L) or water for 6 h. After washing and air drying, seeds were desiccated at 22 °C at a RH of 45-50% to comparable water levels from 50 to 12%. Germination capacity was significantly higher in seeds treated with selenium and desiccated [from 50 to 40, 35 and 30% of water content (WC)] than in water-soaked seeds. At 20% WC, the seeds from both treatments had low viability (approximately 20%). The electrolyte leakage and the MDA content were significantly lower in the embryonic axes of seeds soaked in selenite than in seeds soaked in water. We also found that the activity of glutathione peroxidase (GPX) of embryonic axes from selenium-treated seeds that were not desiccated, or from seeds that were desiccated to 40 and 35% WC, was significantly higher than that of non-treated axes. No difference in GPX activity was detected in cotyledons. This was confirmed by activity staining of GPX after native PAGE of proteins extracted from embryonic axes and cotyledons. An increase in glutathione reductase (GR) activity was also observed in embryonic axes of seeds treated with selenium and dried to 35 and 30% WC compared to non-treated samples. Selenium appeared to have no such effect on cotyledons.     

A role for yeast glutaredoxin genes in selenite-mediated oxidative stress

Since the double Δgrx1Δgrx2 mutant is hypersensitive to selenite we decided to evaluate mechanisms underlying this phenomenon and establish the roles of other components of yeast glutaredoxin system, in particular glutaredoxin 5 in the selenite resistance. We found elevation in the intracellular and mitochondrial superoxide production in the Δgrx1Δgrx2 and Δgrx5 mutants after Se(IV) treatment. The last effect was more pronounced for cells lacking the mitochondrial Grx5 protein. We also recorded selenite-induced increase in the peroxide production in all strains tested. Nonfermentable carbon sources, glycerol and ethanol, augmented selenite toxicity. Hypo- and anoxia protected against the harmful effects of Se(VI). Augmentation of the intracellular levels of two endogenous antioxidants, erythroascorbic acid and glutathione confers resistance to selenite. We recorded a strain-unspecific, selenite-mediated decrease in the level of acid-soluble thiols. Collectively, our data demonstrate that hypersensitivity to the Δgrx1Δgrx2 and Δgrx5 disruptants to selenite is mediated by altered intracellular redox equilibrium.     

Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial permeability transition through thiol-oxidation

Selenium is an essential trace element in mammals and is thought to play a chemopreventive role in human cancer, possibly by inducing tumor cell apoptosis. Mitochondria play a pivotal role in the induction of apoptosis in many cell types. The effects of selenite on mitochondrial function were therefore investigated. Selenite induced the oxidation and cross-linking of protein thiol groups, mitochondrial permeability transition (MPT), a decrease in the mitochondrial membrane potential, and the release of cytochrome c in mitochondria isolated from rat liver. Induction of the MPT by selenite was prevented by cyclosporin A, EGTA, or N-ethylmaleimide. These results thus indicate that selenite induces the MPT as a result of direct modification of protein thiol groups, resulting in the release of cytochrome c and a loss of mitochondrial membrane potential.     

New experimental observation on the relationship of selenium and diabetes mellitus

Selenium shows insulin-mimic properties in vitro and in vivo. However, in this study, a high dose of 4 mg/kg/d selenite orally administered to the alloxan-induced diabetic Kun-Ming mice for 4 wk failed to reduce hyperglycemia. Se contents in plasma and tissues such as the liver, kidney, spleen, and brain were determined and the thiobarbituric acid-reactive substances (TBARS) levels were investigated. The results showed that alloxan-induced diabetes did not cause a significant decrease in Se levels in plasma and the above tissues compared to the normal control, but selenite treatment significantly increased Se levels in plasma, liver, and brain of the selenite-treated diabetic mice compared to the nontreated diabetic mice. In addition, selenite treatment for diabetic mice reduced the TBARS levels in red blood cells (RBCs) compared to the normal and improved the glutathione peroxidase (GSH-Px) levels in RBCs significantly compared to the diabetic control. In conclusion, this study demonstrated that although oral administration of a high dose of selenite had no hypoglycemic effect on diabetic mice in 4 wk, selenite treatment still maintained the antioxidant beneficial effect on the diabetic mice. This study shed more light on the relationship between Se and diabetes.     

Metabolism of subtoxic level of selenite by double-perfused small intestine in rats

Intestinal metabolism of the subtoxic level of selenite in rats was investigated using a double-perfusion system, which is an in situ, in vitro preparation in which the intestinal lumen and its vasculature are perfused simultaneously. The toxicity of sodium selenite was determined by inhibition of 3-O-methyl glucose (3MG) absorption and by histological examination. Levels of 1.2 mM selenite were required to significantly (p<0.05) reduce 3MG intestinal absorption (58±11%, mean±SD). Cation-exchange chromatography was used to determine the chemical forms of Se from selenite after using luminal concentrations of 1–200 μM in vascular perfusates. The chemical forms were selenite, selenodiglutathione (GS-Se-SG), mixed selenoglutathione plus cysteine (GS-Se-CYS), selenodicysteine (CYS-Se-CYS), protein-bound Se, and unidentified selenocompounds. Selenite was the predominant selenocompound found in vascular perfusate, but protein-bound Se was the predominant metabolite from selenite present in the vascular effuents. There was a corresponding increase of all metabolites with increased levels of selenite with time of absorption, but not with increased concentration of luminal selenite.     

Bacterial respiration of arsenic and selenium

Oxyanions of arsenic and selenium can be used in microbial anaerobic respiration as terminal electron acceptors. The detection of arsenate and selenate respiring bacteria in numerous pristine and contaminated environments and their rapid appearance in enrichment culture suggest that they are widespread and metabolically active in nature. Although the bacterial species that have been isolated and characterized are still few in number, they are scattered throughout the bacterial domain and include Gram-positive bacteria, beta, gamma and epsilon Proteobacteria and the sole member of a deeply branching lineage of the bacteria, Chrysiogenes arsenatus. The oxidation of a number of organic substrates (i.e. acetate, lactate, pyruvate, glycerol, ethanol) or hydrogen can be coupled to the reduction of arsenate and selenate, but the actual donor used varies from species to species. Both periplasmic and membrane-associated arsenate and selenate reductases have been characterized. Although the number of subunits and molecular masses differs, they all contain molybdenum. The extent of the environmental impact on the transformation and mobilization of arsenic and selenium by microbial dissimilatory processes is only now being fully appreciated.     

Protein synthesis is not required for the inhibitory effect of selenite on cell colony formation and RNA synthesis

Selenite has been shown to undergo intracellular metabolism that results in its conversion to other low molecular weight Secontaining species and also to its incorporation into a selenocysteine residue in selenoprotein. In order to investigate whether the incorporation into protein is required for the cytotoxic effects of selenite, we have examined whether inhibition of protein synthesis prevents the inhibitory effect of selenite on the ability of cells to form colonies or to synthesize RNA. We have found that treatment of HeLa cells with cycloheximide inhibited protein synthesis by >90% but had no effect on the inhibitory effect of selenite on cell colony formation or RNA synthesis. Since protein synthesis is not necessary for these cytotoxic effects of selenite they are unlikely to result from an increase in the synthesis of selenoproteins.