Environmentally relevant concentrations of selenite trigger reproductive toxicity by affecting oocyte development and promoting larval apoptosis.

As a trace element, selenium (Se) has been widely added to food to maintain the physiological homeostasis of the organism. The adverse effects of Se on the reproduction of zebrafish have been investigated, however, the effects of Se on the maturation and apoptosis of zebrafish oocytes remain unclear. In this study, zebrafish embryos (2 h post fertilization, hpf) were exposed to 0, 12.5, 25, 50, and 100 µg Se/L for 120 days. The results demonstrated that exposure to selenite decreased the gonad-somatic index (GSI) and cumulative production of eggs, inhibited oocyte maturation (OM), and increased oocyte apoptosis in females. Exposure to selenite decreased the contents of sex hormones (E2) in the serum and increased the levels of reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP) in the ovary. Furthermore, exposure to selenite downregulated the transcription level of genes on the HPG axis, decreased the phosphorylation level of CyclinB and the protein content of cAMP-dependent protein kinase (Pka), and upregulated the expression of genes (eif2s1a and chop) and proteins (Grp78, Chop) related to endoplasmic reticulum stress (ERS) and apoptosis. Moreover, maternal exposure to selenite resulted in the apoptosis of offspring and upregulated the content of ROS and the transcription level of genes related to ERS and apoptosis.

Comparison of selenite and selenate in alleviation of drought stress in Nicotiana tabacum L.

Exogenous selenium (Se) improves the tolerance of plants to abiotic stress. However, the effects and mechanisms of different Se species on drought stress alleviation are poorly understood. This study aims to evaluate and compare the different effects and mechanisms of sodium selenate (Na2SeO4) and sodium selenite (Na2SeO3) on the growth, photosynthesis, antioxidant system, osmotic substances and stress-responsive gene expression of Nicotiana tabacum L. under drought stress. The results revealed that drought stress could significantly inhibit growth, whereas both Na2SeO4 and Na2SeO3 could significantly facilitate the growth of N. tabacum under drought stress. However, compared to Na2SeO3, Se application as Na2SeO4 induced a significant increase in the root tip number and number of bifurcations under drought stress. Furthermore, both Na2SeO4 and Na2SeO3 displayed higher levels of photosynthetic pigments, better photosynthesis, and higher concentrations of osmotic substances, antioxidant enzymes, and stress-responsive gene (NtCDPK2, NtP5CS, NtAREB and NtLEA5) expression than drought stress alone. However, the application of Na2SeO4 showed higher expression levels of the NtP5CS and NtAREB genes than Na2SeO3. Both Na2SeO4 and Na2SeO3 alleviated many of the deleterious effects of drought in leaves, which was achieved by reducing stress-induced lipid peroxidation (MDA) and H2O2 content by enhancing the activity of antioxidant enzymes, while Na2SeO4 application showed lower H2O2 and MDA content than Na2SeO3 application. Overall, the results confirm the positive effects of Se application, especially Na2SeO4 application, which is markedly superior to Na2SeO3 in the role of resistance towards abiotic stress in N. tabacum.

A cysteinyl-tRNA synthetase variant confers resistance against selenite toxicity and decreases selenocysteine misincorporation.

Selenocysteine (Sec) is the 21st genetically encoded amino acid in organisms across all domains of life. Although structurally similar to cysteine (Cys), the Sec selenol group has unique properties that are attractive for protein engineering and biotechnology applications. Production of designer proteins with Sec (selenoproteins) at desired positions is now possible with engineered translation systems in Escherichia coli However, obtaining pure selenoproteins at high yields is limited by the accumulation of free Sec in cells, causing undesired incorporation of Sec at Cys codons due to the inability of cysteinyl-tRNA synthetase (CysRS) to discriminate against Sec. Sec misincorporation is toxic to cells and causes protein aggregation in yeast. To overcome this limitation, here we investigated a CysRS from the selenium accumulator plant Astragalus bisulcatus that is reported to reject Sec in vitro Sequence analysis revealed a rare His → Asn variation adjacent to the CysRS catalytic pocket. Introducing this variation into E. coli and Saccharomyces cerevisiae CysRS increased resistance to the toxic effects of selenite and selenomethionine (SeMet), respectively. Although the CysRS variant could still use Sec as a substrate in vitro, we observed a reduction in the frequency of Sec misincorporation at Cys codons in vivo We surmise that the His → Asn variation can be introduced into any CysRS to provide a fitness advantage for strains burdened by Sec misincorporation and selenium toxicity. Our results also support the notion that the CysRS variant provides higher specificity for Cys as a mechanism for plants to grow in selenium-rich soils.

Topical nanodelivery system of lutein for the prevention of selenite-induced cataract.

Cataracts are responsible for half of the world blindness, surgery being the only viable treatment. Lutein, a naturally occurring carotenoid in the eye, has the potential to reduce cataract progression by protecting the eye from photo-oxidative stress. To restore the eye's natural line of defense against photo-oxidative stress, a formulation was developed using zein and poly(lactic-co-glycolic acid) nanoparticles (NPs) embedded in an optimized bioadhesive thermosensitive gel for the delivery of lutein via topical application. Cataracts were induced in Crl:WI rats via selenite injection at 13 days post-partum, followed by 7 days of treatment with free lutein or lutein-loaded NPs administered orally or topically. Cataract severity was significantly reduced in rats treated with topical applications of lutein-loaded NPs compared to the positive control, while no significant differences were observed in rats treated with other lutein formulations including oral and topically applied free lutein.

Selenium species-dependent toxicity, bioavailability and metabolic transformations in Caenorhabditis elegans.

The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys). An inverse relationship was found between toxicity and bioavailability of the Se species, with the organic species displaying a higher bioavailability than the inorganic form, yet being less toxic. Quantitative Se speciation analysis with HPLC/mass spectrometry revealed a partial metabolism of SeMet and MeSeCys. In SeMet exposed worms, identified metabolites were Se-adenosylselenomethionine (AdoSeMet) and Se-adenosylselenohomocysteine (AdoSeHcy), while worms exposed to MeSeCys produced Se-methylselenoglutathione (MeSeGSH) and γ-glutamyl-MeSeCys (γ-Glu-MeSeCys). Moreover, the possible role of the sole selenoprotein in the nematode, thioredoxin reductase-1 (TrxR-1), was studied comparing wildtype and trxr-1 deletion mutants. Although a lower basal Se level was detected in trxr-1 mutants, Se toxicity and bioavailability following acute exposure was indistinguishable from wildtype worms. Altogether, the current study demonstrates the suitability of C. elegans as a model for Se species dependent toxicity and metabolism, while further research is needed to elucidate TrxR-1 function in the nematode.

Selenium accumulation and the effects on the liver of topmouth gudgeon Pseudorasbora parva exposed to dissolved inorganic selenium.

Selenite(IV) and selenate(VI) are the major forms of Se in aquatic ecosystem. In this study, Pseudorasbora parva were exposed to 10, 200 and 1000 µg L-1 selenite and selenate for 28 days. Selenium accumulation, antioxidant enzyme levels, glutathione concentrations, lipid peroxidation and histology were evaluated in livers following exposure. Our results showed that Se(IV) and Se(VI) caused different accumulation patterns in the liver, with a more rapid accumulation of Se with Se(IV) treatment. Both Se species increased hepatic lipid peroxidation after 14 and 28 d (~ 30%). Among the antioxidants examined, the activity of SOD (except day 28) and the cellular levels of GSH were induced by 72-137% at lower concentrations, while the activity of GST was at least 24% lower than that of the control at 200 and 1000 µg L-1 for both Se species at all sampling points. Both forms of Se reduced the hepatosomatic index at 1000 µg L-1 after 28 d. In addition, marked histopathological alterations (10-31%) were observed in the liver of P. parva after exposure to both Se species, with higher frequency in the Se(IV) exposed fish. Liver local necrosis was observed only in the liver of fish exposed to 1000 µg L-1 of Se(IV) (~ 20%). Our results suggest that the ecological impacts of dissolved Se in this freshwater species may also contribute to overall toxicity.

Effect of hesperetin derivatives on the development of selenite­induced cataracts in rats.

Cataracts are a major cause of blindness worldwide. As anti­cataract pharmaceutical therapies require long­term treatment, identifying anti­cataract compounds that are ubiquitous in the human diet, have no adverse effects and are affordable, is of paramount importance. The present study focused on hesperetin and its derived compounds, hesperetin stearic acid ester (Hes­S) and hesperetin oleic acid ester (Hes­O), in order to investigate their therapeutic potential to treat cataracts in a selenite animal model. Thirteen­day­old Sprague Dawley rats were divided into 12 groups. Animals in groups 1 and 7 were subcutaneously injected with vehicle, those in groups 2 and 8 were administered hesperetin, those in groups 3 and 9 received stearic acid, those in groups 4 and 10 were injected with oleic acid, those in groups 5 and 11 were administered Hes­S, and those in groups 6 and 12 received Hes­O (10 nmol/kg body weight on days 0, 1 and 2). Animals in groups 7 to 12 were treated with sodium selenite (20 µmol/kg body weight given 4 h following the test compound treatment on day 0) to induce cataract. On day 6, rats had less severe central opacities and lower stage cataracts than rats in the selenite treatment­only control groups. The levels of glutathione (GSH) and ascorbic acid (AsA) in lenses with selenite­induced cataracts declined to one­third of that of controls, and the reduction in GSH and AsA levels was rescued following hesperetin, Hes­S or Hes­O treatment, with concentrations remaining to 70­80% of that of controls. However, there were no changes in the plasma levels of GSH and AsA following treatments. Administration of either hesperetin or hesperetin­derived compounds prevented the reduction of chaperone activity in the lens, and rats treated with Hes­S or Hes­O treatment had significantly greater chaperone activity than hesperetin­treated rats. Collectively, these results suggested that hesperetin and hesperetin­derived compounds may be novel drug compounds that have the potential to prevent or delay the onset of cataracts.

Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats.

BACKGROUND: The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups. METHODS: Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins. RESULTS: Morphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite- injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA. CONCLUSIONS: The data suggest that NACA has the potential to significantly improve vision and decrease the burden of cataract-related loss of function. Prevention and reversal of cataract formation could have a global impact. Development of pharmacological agents like NACA may eventually prevent cataract formation in high-risk populations and may prevent progression of early-stage cataracts. This brings a paradigm shift from expensive surgical treatment of cataracts to relatively inexpensive prevention of vision loss.

The importance of glutathione and phytochelatins on the selenite and arsenate detoxification in Arabidopsis thaliana.

We investigated the role of glutathione (GSH) and phytochelatins (PCs) on the detoxification of selenite using Arabidopsis thaliana. The wild-type (WT) of Arabidopsis thaliana and its mutants (glutathione deficient Cad 2-1 and phytochelatins deficient Cad 1-3) were separately exposed to varying concentrations of selenite and arsenate and jointly to both toxicants to determine their sensitivities. The results of the study revealed that, the mutants were about 20-fold more sensitive to arsenate than the WT, an indication that the GSH and PCs affect arsenate detoxification. On the contrary, the WT and both mutants showed a similar level of sensitivity to selenite, an indication that the GSH and PCs do not significantly affect selenite detoxification. However, the WT is about 8 times more sensitive to selenite than to arsenate, and the mutants were more resistant to selenite than arsenate by a factor of 2. This could not be explained by the accumulation of both elements in roots and shoots in exposure experiments. The co-exposure of the WT indicates a synergistic effect with regards to toxicity since selenite did not induce PCs but arsenic and selenium compete in their PC binding as revealed by speciation analysis of the root extracts using HPLC-ICP-MS/ESI-MS. In the absence of PCs an antagonistic effect has been detected which might suggest indirectly that the formation of Se glutathione complex prevent the formation of detrimental selenopeptides. This study, therefore, revealed that PC and GSH have only a subordinate role in the detoxification of selenite.

A low level of dietary selenium has both beneficial and toxic effects and is protective against Cd-toxicity in the least killifish Heterandria formosa.

As an essential element, selenium (Se) is beneficial at low levels yet toxic at high levels. The present study assessed the effects of dietary exposure to Se in the least killifish Heterandria formosa, and investigated how this exposure influences the effects of a subsequent exposure to cadmium (Cd). The fish were pre-exposed to an environmentally relevant concentration (2 µg g(-1) dry wt) of dietary selenite (Se(4+)) or seleno-l-methionine (Se-Met) for 10 d. The same fish were then exposed to 0.5 mg L(-1) of Cd for 5 d. Both Se(IV) and Se-Met rapidly accumulated in H. formosa. Results for the two Se species were generally similar in this study. Fish exposed to Se had lower levels of lipid peroxidation (measured as levels of thiobarbituric acid reactive substances or TBARS) and a higher catalase (CAT) activity. In contrast, their Na(+)/K(+)-ATPase activity was reduced. The Cd exposure resulted in an increase in lipid peroxidation and decreases in the activities of catalase and Na(+)/K(+)-ATPase. The Cd-exposed H. formosa that were pre-exposed to Se had lower Cd body burdens, less lipid peroxidation, and higher catalase activity, than did fish not pre-exposed to Se. The Se exposure did not have a protective effect on the Cd-induced reduction in Na(+)/K(+)-ATPase activity. These results clearly demonstrate that a Se-enriched diet reduces some (but not all) forms of Cd-toxicity and that Se can simultaneously have beneficial and detrimental effects, making it difficult to predict the net outcome of changes in dietary Se levels for fish.

Superoxide generated from the glutathione-mediated reduction of selenite damages the iron-sulfur cluster of chloroplastic ferredoxin.

Selenium assimilation in plants is facilitated by several enzymes that participate in the transport and assimilation of sulfate. Manipulation of genes that function in sulfur metabolism dramatically affects selenium toxicity and accumulation. However, it has been proposed that selenite is not reduced by sulfite reductase. Instead, selenite can be non-enzymatically reduced by glutathione, generating selenodiglutathione and superoxide. The damaging effects of superoxide on iron-sulfur clusters in cytosolic and mitochondrial proteins are well known. However, it is unknown if superoxide damages chloroplastic iron-sulfur proteins. The goals of this study were twofold: to determine whether decreased activity of sulfite reductase impacts selenium tolerance in Arabidopsis, and to determine if superoxide generated from the glutathione-mediated reduction of selenite damages the iron-sulfur cluster of ferredoxin. Our data demonstrate that knockdown of sulfite reductase in Arabidopsis does not affect selenite tolerance or selenium accumulation. Additionally, we provide in vitro evidence that the non-enzymatic reduction of selenite damages the iron-sulfur cluster of ferredoxin, a plastidial protein that is an essential component of the photosynthetic light reactions. Damage to ferredoxin's iron-sulfur cluster was associated with formation of apo-ferredoxin and impaired activity. We conclude that if superoxide damages iron-sulfur clusters of ferredoxin in planta, then it might contribute to photosynthetic impairment often associated with abiotic stress, including toxic levels of selenium.

Cytotoxic activity of selenosulfate versus selenite in tumor cells depends on cell line and presence of amino acids.

Based on acute cytotoxicity studies, selenosulfate (SeSO3 (-)) has been suggested to possess a generally higher toxic activity in tumor cells than selenite. The reason for this difference in cytotoxic activity remained unclear. In the present study, cytotoxicity tests with human hepatoma (HepG2), malignant melanoma (A375), and urinary bladder carcinoma cells (T24) showed that the selenosulfate toxicity was very similar between all three tested cell lines (IC50 6.6-7.1 µM after 24 h). It was largely independent of exposure time and presence or absence of amino acids. What changed, however, was the toxicity of selenite, which was lower than that of selenosulfate only for HepG2 cells (IC50 > 15 µM), but similar to and higher than that of selenosulfate for A375 (IC50 4.7 µM) and T24 cells (IC50 3.5 µM), respectively. Addition of amino acids to T24 cell growth medium downregulated short-term selenite uptake (1.5 versus 12.9 ng Se/10(6) cells) and decreased its cytotoxicity (IC50 8.4 µM), rendering it less toxic than selenosulfate. The suggested mechanism is a stronger expression of the xc (-) transport system in the more sensitive T24 compared to HepG2 cells which creates a reductive extracellular microenvironment and facilitates selenite uptake by reduction. Selenosulfate is already reduced and so less affected. The cytotoxic activity of selenosulfate and selenite to tumor cells therefore depends on the sensitivity of each cell line, supplements like amino acids as well as the reductive state of the extracellular environment.

Selenite induces DNA damage and specific mitochondrial degeneration in human bladder cancer cells.

We have investigated the cytotoxicity and specific effects of selenite in human bladder cancer cell line RT-112 and its clonogenic variant RT-112 HB. Selenite inhibited cell growth and proliferation in both cell lines. Treated cells developed extensive vacuolization which was dose independent but occurring in differing time frames. Ultrastructure analysis revealed that the observed vacuoles are damaged mitochondria and potentially other subcellular compartments. Selenite-specific effects on mitochondria were further confirmed by mitochondrial membrane potential analysis, changes in ATP production and generation of superoxide. Simultaneously, selenite induced DNA damage in treated cells with activation of p53, PARP-1 and JNK and suppressed autophagy. Cells ultimately died via a combination of apoptosis, necrosis and a distinct type of cell death featuring "vacuolar shrinkage", loss of adherence and absence of secondary necrosis as well as other classical markers of either apoptosis or autophagy. The significant presence of so called necroptosis was also not confirmed as the specific inhibitor necrostatin-1 could not prevent cell death. These results thus confirm the toxicity of selenite in bladder cancer cells while pointing at potentially new mechanism of action of this compound in this model.

Germinating Peanut (Arachis hypogaea L.) Seedlings Attenuated Selenite-Induced Toxicity by Activating the Antioxidant Enzymes and Mediating the Ascorbate-Glutathione Cycle.

Selenite can enhance the selenium nutrition level of crops, but excessive selenite may be toxic to plant growth. To elucidate the mechanisms underlying the role of selenite in production and detoxification of oxidative toxicity, peanut seedlings were developed with sodium selenite (0, 3, and 6 mg/L). The effects of selenite on antioxidant capacity, transcript levels of antioxidant enzyme genes, and enzyme activities in hypocotyl were investigated. The CuZn-SOD, GSH-Px, GST, and APX gene expression levels and their enzyme activities in selenite treatments were 1.0-3.6-fold of the control. Selenite also significantly increased the glutathione and ascorbate concentrations by mediating the ascorbate-glutathione cycle, and the selenite-induced hydrogen peroxide may act as a second messenger in the signaling pathways. This work has revealed a complex antioxidative response to selenite in peanut seedling. Understanding these mechanisms may help future research in increasing selenite tolerance and selenium accumulation in peanut and other crops.

Cerebral Area Differential Redox Response of Neonatal Rats to Selenite-Induced Oxidative Stress and to Concurrent Administration of Highbush Blueberry Leaf Polyphenols.

Our goal was to delineate the mechanisms of selenite-induced oxidative stress in neonatal rats and investigate the potential of blueberry leaf polyphenols to counteract the induced stress. Vaccinium corymbosum leaf decoction (BLD) was analyzed by UPLC-MS and LC-DAD, along with its in vitro antioxidant activity (DPPH radical scavenging, FRAP, ferrous chelation). Newborn suckling Wistar rats were randomly divided into three groups: 'Se' and 'SeBLD' received 20 µmol Na2SeO3/kg BW subcutaneously (PN day 10); 'SeBLD' received 100 mg dry BLD/kg BW intraperitoneally (PN11 and 12) and Group 'C' received normal saline. Βiochemical analysis revealed tissue-specific effects of selenite. Brain as a whole was more resistant to selenite toxicity in comparison to liver; midbrain and cerebellum were in general not affected, but cortex was moderately disturbed. Liver lipid peroxidation, GSH, SOD, CAT, GPx were significantly affected, whereas proteolytic activity was not. BLD, which is rich in chlorogenic acid and flavonols (especially quercetin derivatives), exerted significant antioxidant protective effects in all regions. In conclusion, we provide for the first time an insight to the neonatal rat cerebral and liver redox response against a toxic selenite dose and blueberry leaf polyphenols.

Trans-sulfuration Pathway Seleno-amino Acids Are Mediators of Selenomethionine Toxicity in Saccharomyces cerevisiae.

Toxicity of selenomethionine, an organic derivative of selenium widely used as supplement in human diets, was studied in the model organism Saccharomyces cerevisiae. Several DNA repair-deficient strains hypersensitive to selenide displayed wild-type growth rate properties in the presence of selenomethionine indicating that selenide and selenomethionine exert their toxicity via distinct mechanisms. Cytotoxicity of selenomethionine decreased when the extracellular concentration of methionine or S-adenosylmethionine was increased. This protection resulted from competition between the S- and Se-compounds along the downstream metabolic pathways inside the cell. By comparing the sensitivity to selenomethionine of mutants impaired in the sulfur amino acid pathway, we excluded a toxic effect of Se-adenosylmethionine, Se-adenosylhomocysteine, or of any compound in the methionine salvage pathway. Instead, we found that selenomethionine toxicity is mediated by the trans-sulfuration pathway amino acids selenohomocysteine and/or selenocysteine. Involvement of superoxide radicals in selenomethionine toxicity in vivo is suggested by the hypersensitivity of a Δsod1 mutant strain, increased resistance afforded by the superoxide scavenger manganese, and inactivation of aconitase. In parallel, we showed that, in vitro, the complete oxidation of the selenol function of selenocysteine or selenohomocysteine by dioxygen is achieved within a few minutes at neutral pH and produces superoxide radicals. These results establish a link between superoxide production and trans-sulfuration pathway seleno-amino acids and emphasize the importance of the selenol function in the mechanism of organic selenium toxicity.

Selenite-induced toxicity in cancer cells is mediated by metabolic generation of endogenous selenium nanoparticles.

Selenite has been a touted cancer chemopreventative agent but generates conflicting outcomes. Multiple mechanisms of selenite cytotoxicity in cancer cells are thought to be induced by metabolites of selenite. We observed that intracellular metabolism of selenite generates endogenous selenium nanoparticles (SeNPs) in cancer cells. Critical proteins that bind with high affinity to elemental selenium during SeNPs self-assembly were identified through proteomics analysis; these include glycolytic enzymes, insoluble tubulin, and heat shock proteins 90 (HSP90). Sequestration of glycolytic enzymes by SeNPs dramatically inhibits ATP generation, which leads to functional and structural disruption of mitochondria. Transcriptome sequencing showed tremendous down-regulation of mitochondrial respiratory NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and ATP synthase (complex V) in response to glycolysis-dependent mitochondrial dysfunction. Sequestration of insoluble tubulin led to microtubule depolymerization, altering microtubule dynamics. HSP90 sequestration led to degradation of its downstream effectors via autophagy, ultimately resulting in a cell-signaling switch to apoptosis. Additionally, the surface effects of SeNPs generated oxidative stress, thus contributing to selenite cytotoxicity. Herein, we reveal that the multiple mechanisms of selenite-induced cytotoxicity are caused by endogenous protein-assisted self-assembly of SeNPs and suggest that endogenous SeNPs could potentially be the primary cause of selenite-induced cytotoxicity.

Effects of selenium on development, survival, and accumulation in the honeybee (Apis mellifera L.).

Apis mellifera L. (Hymenoptera: Apidae) is an important agricultural pollinator in the United States and throughout the world. In areas of selenium (Se) contamination, honeybees may be at risk because of the biotransfer of Se from plant products such as nectar and pollen. Several forms of Se can occur in accumulating plants. In the present study, the toxicity of 4 compounds (selenate, selenite, methylselenocysteine, and selenocystine) to honeybee adult foragers and larvae was assessed using dose-response bioassays. Inorganic forms were more toxic than organic forms for both larvae (lethal concentration [LC50] selenate = 0.72 mg L(-1) , LC50 selenite = 1.0 mg L(-1) , LC50 methylselenocysteine = 4.7 mg L(-1) , LC50 selenocystine = 4.4 mg L(-1) ) and foragers (LC50 selenate = 58 mg L(-1) , LC50 selenite = 58 mg L(-1) , LC50 methylselenocysteine = 161 mg L(-1) , LC50 selenocystine = 148 mg L(-1) ). Inorganic forms of Se caused rapid mortality, and organic forms had sublethal effects on development. Larvae accumulated substantial amounts of Se only at the highest doses, whereas foragers accumulated large quantities at all doses. The present study documented very low larval LC50 values for Se; even modest transfer to brood will likely cause increased development times and mortality. The toxicities of the various forms of Se to honeybee larvae and foragers are discussed in comparison with other insect herbivores and detritivores.

Selenoprotein W as biomarker for the efficacy of selenium compounds to act as source for selenoprotein biosynthesis.

Selenium is an essential trace element and, like all elements, present in many different compounds with unequivocal functions. This fact is only sporadically mentioned when recommended intake or supplementation is indicated just as "selenium." In mammals, selenium is an integral part of selenoproteins as selenocysteine. Selenocysteine is formed from serine at the respective tRNA((ser)sec), a reaction that requires selenophosphate formed from selenide and ATP. Thus, only compounds that can be metabolized into selenide can serve as sources for selenoprotein biosynthesis. We therefore tested the ability of selenium compounds such as sodium selenite, methylseleninic acid (MeSeA), Se-methyl selenocysteine, and selenomethionine to increase the activity, protein, or mRNA levels of commonly used biomarkers of the selenium status, glutathione peroxidase-1 (GPx1) and thioredoxin reductase, and of putatively new biomarkers, selenoprotein W1 (SepW1), selenoprotein H, and selenoprotein 15 in three different cell lines. Selenite and MeSeA were most efficient in increasing all markers tested, whereas the other compounds had only marginal effects. Effects were higher in the noncancerous young adult mouse colon cells than in the cancer cell lines HepG2 and HT-29. At the protein level, SepW1 responded as well as GPx1 and at the mRNA level, even better. Thus, the outcome of selenium treatment strongly depends on the chemical form, the cell type, and the biomarker used for testing efficacy.