Selenium Toxicity Research Articles

Acumulación de selenio en setas silvestres comestibles: captación y toxicidadSelenium accumulation in wild edible mushrooms: uptake and toxicity

Selenium is considered as a trace element metal, but in excessive doses it becomes toxic for the consumer's health. In this study, the goal was to determine the accumulation capacity of selenium in edible mushrooms in relation to some factors and their possible toxicological implications. Edible mushrooms (97 samples of 14 species) were collected in Lugo, Galicia (Spain). Anatomical parts, hymenophore and the rest of the fruiting body, were processed by digestion in acid medium in a microwave oven and analyzed by inductively coupled plasma-optical emission spectrometer. Boletus pinicola and Boletus edulis reached the highest mean selenium contents in hymenophore with values of 74.93 and 52.7 mg/kg dry weight, respectively. Organic matter in growth soil between 12–16% favoured its uptake. Finally, taking into account the dose of chronic toxicity of selenium, relatively close to the dietary recommendations (WHO), and the concentrations obtained in the studied mushrooms, a moderate consumption of some species of Boletus is recommended.

Model mechanisms of sulfhydryl oxidation by methyl- and benzeneseleninic acid, inhibitors of zinc-finger transcription factors

The toxicity of selenium is a major barrier to its application to the prevention of cancer, cardiovascular disease, and other chronic ailments. Organic seleninic acids, as well as other reducible selenium compounds, have been shown to react with biological sulfhydryls to disrupt a variety of biochemical signaling pathways, including transcription and recognition by zinc-finger proteins. Using density-functional theory (DFT) and solvent-assisted proton exchange, the thiol reduction mechanisms of methyl- and benzeneseleninic acid have been modeled as distinct two-step pathways with intermediates as either a seleninyl sulfide or a hypervalent selenurane. The activation barrier for the first step to the selenurane intermediate is 10-13kcal/mol lower than the seleninyl sulfide. For the second step, reduction of the selenurane is slightly more energetically favorable than for the seleninyl sulfide, primarily due to the implicit solvation correction. The barrier for step two using either intermediate is greater than that of the first step which is consistent with experimental studies that assign the reduction of the intermediate as the rate-determining step. The summary of the DFT results suggest that the reaction pathway is (1) addition of thiol to the seleninic acid to form a short-lived selenurane; (2) rearrangement of the selenurane to the seleninyl sulfide; and (3) reduction of the seleninyl sulfide by the second equivalent of thiol.

Selenite causes cytotoxicity in rainbow trout ( Oncorhynchus mykiss) hepatocytes by inducing oxidative stress

Selenium is an essential micronutrient to freshwater fish, but can be very toxic at slightly above the threshold level. The liver is known to be the major site of selenium accumulation and metabolism in fish. Recent evidence from mammalian systems suggests that oxidative damage is an important mechanism of selenium toxicity; however this phenomenon has not been investigated in-depth in fish, either in vivo or in vitro. Therefore, the present study was designed to investigate whether selenium (as selenite) exposure causes cytotoxicity in fish by inducing oxidative stress. We used isolated hepatocytes in primary culture from freshwater rainbow trout ( Oncorhynchus mykiss) as the model in vitro experimental system. The 24 h LD 50 of selenite to trout hepatocytes was found to be 587 μM. In order to evaluate the dose-dependent response patterns of various oxidative stress parameters, the trout hepatocytes were exposed to three different doses of selenite [50, 100 and 200 μM (corresponding to approximately 10%, 20% and 35% of 24 h LD 50)] in addition to control (0 μM of selenite) for 24 h. We observed an induction of catalase (CAT) and superoxide dismutase (SOD) activities at 50 and 100 μM of selenite exposure, but not at 200 μM, relative to the control. In contrast, the induction of glutathione peroxidase (GPx) activity was recorded at 100 and 200 μM exposure doses, but not at 50 μM. We also demonstrated that selenite exposure (100–200 μM) increased intracellular ROS formation at an early stage (2 h). The reduced to oxidized glutathione ratio (GSH:GSSG) decreased sharply with increasing selenite dose, indicating the loss of cellular reducing capacity. The cellular lipid peroxidation tended to increase with increasing selenite exposure dose, indicating the occurrence of membrane damage. A 20–40% decrease in cell viability was observed at 100 and 200 μM of selenite exposure. The increase in cell death was associated with a significant increase of caspase-3/7 activity, suggesting the induction of apoptosis. Overall, the present study suggests that selenite exposure at high level causes oxidative damage to trout hepatocytes, probably by inducing the imbalance of intracellular glutathione (GSH) redox.

Water Pollution Related to Agricultural, Industrial, and Urban Activities, and its Effects on the Food Chain: Case Studies from Punjab

In Punjab, a northwestern state of India, groundwater is depleting at a fast rate because of its excessive use and mismanagement. Contamination of groundwater and water bodies from geogenic and anthropogenic sources is also becoming a serious problem. Selenium (Se) toxicity is prevalent in 1,000 ha in Hoshiarpur and Nawanshahar districts where about 11 and 4% of groundwater samples were found unfit for drinking and irrigation purposes, respectively. About 9 and 66% groundwater samples of the Ludhiana and Bathinda districts, respectively, had fluoride concentration more than the safe limit of 1 mg l −1. In the Bathinda district, 15–44% of groundwater samples had boron more than the maximum permissible limit of 2 mg l −1. Arsenic concentration in alluvial aquifers of Punjab ranged from 4 to 688 μg l −1, and the majority of them were found unfit for human consumption considering maximum permissible limit of 10 μg l −1. Excessive applications of fertilizers, manures, and agrichemicals to field and vegetable c...

Bioaccumulation and toxicity of selenium compounds in the green alga Scenedesmus quadricauda

BackgroundSelenium is a trace element performing important biological functions in many organisms including humans. It usually affects organisms in a strictly dosage-dependent manner being essential at low and toxic at higher concentrations. The impact of selenium on mammalian and land plant cells has been quite extensively studied. Information about algal cells is rare despite of the fact that they could produce selenium enriched biomass for biotechnology purposes.ResultsWe studied the impact of selenium compounds on the green chlorococcal alga Scenedesmus quadricauda. Both the dose and chemical forms of Se were critical factors in the cellular response. Se toxicity increased in cultures grown under sulfur deficient conditions. We selected three strains of Scenedesmus quadricauda specifically resistant to high concentrations of inorganic selenium added as selenite (Na2SeO3) – strain SeIV, selenate (Na2SeO4) – strain SeVI or both – strain SeIV+VI. The total amount of Se and selenomethionine in biomass increased with increasing concentration of Se in the culturing media. The selenomethionine made up 30–40% of the total Se in biomass. In both the wild type and Se-resistant strains, the activity of thioredoxin reductase, increased rapidly in the presence of the form of selenium for which the given algal strain was not resistant.ConclusionThe selenium effect on the green alga Scenedesmus quadricauda was not only dose dependent, but the chemical form of the element was also crucial. With sulfur deficiency, the selenium toxicity increases, indicating interference of Se with sulfur metabolism. The amount of selenium and SeMet in algal biomass was dependent on both the type of compound and its dose. The activity of thioredoxin reductase was affected by selenium treatment in dose-dependent and toxic-dependent manner. The findings implied that the increase in TR activity in algal cells was a stress response to selenium cytotoxicity. Our study provides a new insight into the impact of selenium on green algae, especially with regard to its toxicity and bioaccumulation.

Methionine, vitamin E, and selenium toxicity.

Methionine, vitamin E, and selenium toxicity.

Effect of Selenium-Rich Wheat on Rat Spermatogenesis/Wirkung von Selen-haltigem Weizen auf die Spermatogenese der Ratte

Wheat cultivated in seleniferous soils of some districts of Punjab/India contained on an average 12.5 ppm selenium. These grains when fed for 4 weeks to laboratory rats, were found to cause reduction of testicular weights and interruption of spermatogenesis. Seminiferous tubules were severely affected and contained spermatogenic cells at different stages of regression. The population of spermatids was first to be affected as they showed clumping leading to the formation of giant cells. Interstitial tissue in the testes of rats fed on seleniferous wheat grains appeared oedematous and widened than that of controls. The results, therefore, revealed that selenium toxicity, in addition to its known effects in female rats, has an adverse effect on reproduction in the male rats.

High-Dose Selenium for the Mitigation of Radiation Injury: A Pilot Study in a Rat Model

The purpose of this study was to evaluate in an animal model the safety and efficacy of dietary supplementation with high doses of selenium for the mitigation of the type of radiation injury that might be sustained during a nuclear accident or an act of radiological terrorism. Age-matched male rats were exposed to 10 Gy (single dose) of total-body irradiation (TBI) followed by a syngeneic bone marrow transplant, then randomized to standard drinking water or drinking water supplemented with sodium selenite or seleno-l-methionine. At 21 weeks after TBI, most rats on standard drinking water had severe renal failure with a mean blood urea nitrogen (BUN) level of 124 +/- 29 mg/dl (geometric mean +/- SE) whereas rats on selenium-supplemented drinking water (100 microg/day) had a mean BUN level of 67 +/- 12 mg/dl. The mitigating effect of selenium was confirmed by histopathological analyses. None of the animals on high-dose selenium showed signs of selenium toxicity. Our results suggest that dietary supplementation with high-dose selenium may provide a safe, effective and practical way to mitigate radiation injury to kidneys.

Biodynamics, Subcellular Partitioning, and Ultrastructural Effects of Organic Selenium in a Freshwater Bivalve

Selenium is a trace element characterized by concentrations that narrowly range between being essential and being toxic. Even though inorganic selenite and selenate are the predominantchemicalforms ofSe in surfacewaters, the toxicity of Se to aquatic organisms is mostly governed by the bioavailability of organic selenium within food webs. The present study was designed to evaluate organic selenium bioaccumulation and toxicity patterns in the freshwater sentinel species Corbicula fluminea. Waterborne selenomethionine (SeMet) exposure was used to mimic dietary organo-Se uptake. Our results demonstrate that SeMet is accumulated to a relatively high extentwith a concentration factor of 770 (wet weight basis). Higher uptake than depuration rates suggest that bivalves deal with high Se amounts using a strategy of detoxification based on Se sequestration that could involve granules, as shown by a strong increase of Se in the particulate subcellular fraction. Selenium is persistent in the cytosol of bivalves exposed to SeMet where it is found in proteins of a wide range of molecular mass, indicating a possible replacement of methionine by selenomethionine. A subsequent alteration of protein function might be one of the mechanisms of Se toxicity that could explain the histopathological effects we observed in gills by using transmission electronic microscopy. Those analyses showed changes in gill filament ultrastructure and suggested mitochondria asthefirsttargetfor SeMet cytotoxicity, with alterations of the outer membrane and of cristae morphology. Organo-Se would thus not only be toxic via indirect mechanisms of maternal transfer as it was suggested for fish but also directly. Our results on Se distribution agree with studies that used dietary Se transfer, and highlight the relevance (and less expensive way) of using SeMet water-only exposure protocols to mimic the real environment.

Toxicity and Oxidative Stress of Organic and Inorganic Selenium Administered to Rats Daily with Sub-Median Lethal Dose

Toxicity and Oxidative Stress of Organic and Inorganic Selenium Administered to Rats Daily with Sub-Median Lethal Dose

Analysis of Saccharomyces cerevisiae null allele strains identifies a larger role for DNA damage versus oxidative stress pathways in growth inhibition by selenium

Selenium toxicity is a growing environmental concern due to widespread availability of high-dose selenium supplements and the development of high-selenium agricultural drainage basins. To begin to analyze the effects of selenium toxicity at the genetic level, we have systematically determined which genes are involved in responding to high environmental selenium using a collection of viable haploid null allele strains of Saccharomyces cerevisiae representing three major stress pathways: the RAD9-dependent DNA repair pathway, the RAD6/RAD18 DNA damage tolerance pathway, and the oxidative stress pathway. A total of 53 null allele strains were tested for growth defects in the presence of a range of sodium selenite and selenomethionine (SeMet) concentrations. Our results show that approximately 64-72% of the strains lacking RAD9-dependent DNA repair or RAD6/RAD18 DNA damage tolerance pathway genes show reduced growth in sodium selenite versus approximately 28-36% in SeMet. Interestingly both compounds reduced growth in approximately 21-25% of the strains lacking oxidative stress genes. These data suggest that both selenite and SeMet are likely inducing DNA damage by generating reactive species. The anticipated effects of loss of components of the oxidative stress pathway were not observed, likely due to apparent redundancies in these gene products that may keep the damaging effects in check.

The essential toxin: The changing perception of selenium in environmental sciences

During the last decades, the perception of selenium has undergone substantial changes. While its toxic effects were recognized causing hair and hoof loss in animals during the 1930s, its essential role in microbial, animal and human metabolism has been recognized later, i.e. with the discovery of selenium deficiency causing “white muscle disease” in feedstock in the 1950s. Nowadays, the positive effect of systematic selenium supplementation is discussed in manifold topics such as cancer or diabetes prevention and avian influenza susceptibility. Treatment of selenium containing waste streams poses a notable challenge to environmental engineers, and to date no ultimate solution has been found for e.g. the selenium contamination in agricultural areas of the western USA. For the future, selenium contamination carries an imminent danger, if the increasing energy demand is covered by fossil fuel combustion, which will lead to major selenium emission and toxicity. This review presents current knowledge of selenium’s role in environmental sciences and outlines potentially feasible treatment options targeting a variety of selenium contaminated waste streams.

Effects of a selenium-enriched diet on antioxidant response in adult crayfish ( Procambarus clarkii)

Many diets employed in aquaculture are enriched with selenium to improve the diet quality and its conservation. The aim of the study was to investigate the effects of a diet enriched in selenium (1.21 mg kg −1) on the antioxidant response of Procambarus clarkii (Girard, 1852). Crayfish fed a diet with lower selenium content (0.30 mg kg −1) were the control. Selenium accumulation, enzymatic activities, and total glutathione were evaluated in hepatopancreas of adults of both sexes fed with both diets for 50 days at two experimental times ( T 30, T 50 days). Treated females exhibited the highest selenium bioaccumulation during both experimental times, while treated males displayed the highest selenium concentration after 30 days, compared to control crayfish. A sex-related difference was found for the response of the analyzed enzymes in the selenium diet-treated specimens. In fact, superoxide dismutase, glutathione peroxidase and glyoxalase I activities in males were more sensitive compared with females, showing depleted activities in both experimental times. Catalase activity was induced in females ( T 50), while glutathione S-transferase activity was the highest in treated females and the lowest in treated males, compared with own controls. Only glutathione reductase activity and glutathione content showed the same trend in both sexes, which were both lowered in treated specimens, when compared with control crayfish. This result might be due to the effect of selenium toxicity on this freshwater species. Males and females of P. clarkii showed a different susceptibility to the prooxidant effects in a Se-enriched diet.

Solution NMR Structure of Selenium-binding Protein from Methanococcus vannielii

Selenium is an important nutrient. The lack of selenium will suppress expression of various enzymes that will lead to cell abnormality and diseases. However, high concentrations of free selenium are toxic to the cell because it adversely affects numerous cell metabolic pathways. In Methanococcus vannielii, selenium transport in the cell is established by the selenium-binding protein, SeBP. SeBP sequesters selenium during transport, thus regulating the level of free selenium in the cell, and delivers it specifically to the selenophosphate synthase enzyme. In solution, SeBP is an oligomer of 8.8-kDa subunits. It is a symmetric pentamer. The solution structure of SeBP was determined by NMR spectroscopy. Each subunit of SeBP is composed of an alpha-helix on top of a 4-stranded twisted beta-sheet. The stability of the five subunits stems mainly from hydrophobic interactions and supplemented by hydrogen bond interactions. The loop containing Cys(59) has been shown to be important for selenium binding, is flexible, and adopts multiple conformations. However, the cysteine accessibility is restricted in the structure, reducing the possibility of the binding of free selenium readily. Therefore, a different selenium precursor or other factors might be needed to facilitate opening of this loop to expose Cys(59) for selenium binding.

Selenium toxicosis assessment ( in vivo and in vitro) and the protective role of vitamin B12 in male quail ( Coturnix Coturnix)

The present study was undertaken to elucidate the toxicity induced by sodium selenite in male quail through in vivo and in vitro studies and the role played by vitamin B12 in alleviating selenium toxicity. Administration of selenite orally for 1 month induced hepatic oxidative damage. Selenite decreased body weight gain and increased relative liver weight. Selenite reduced hemoglobin and iron concentrations and elevated total bilirubin concentration. Serum transaminases and alkaline phosphatase activities were increased in selenium-intoxicated quails. Total protein concentration was decreased associated with the appearance of prealbumin fraction, an increased γ-globulin and a decreased α- and β-globulins. The highest level of selenium was found in liver followed by kidney, testis, faeces and blood. Supplementation of vitamin B12 orally for 1 month simultaneously with selenite caused less marked biological alteration in the investigated parameters. In vitro study using isolated quail hepatocytes incubated with sodium selenite showed a dose-dependent response for toxicity markers. These results suggest that selenosis can be reduced by vitamin B12 supplementation.

Cyberspace Chat

1. Sharon A. Keene, MD 1. Tucson, Arizona </br>![][1]</img> A warning about Total Body Mega Formula: nutritional supplement causes selenium toxicity and associated hair loss Recently the following cyberchat report occurred regarding extreme hair loss caused by a nutritional supplement

Selenium Toxicity: A Case of Selenosis Caused by a Nutritional Supplement

Background: Selenium is a nonmetal element that serves vital roles in normal physiologic function. Substantial toxicity can occur with excessive selenium consumption. In March 2008, the U.S. Food and Drug Administration (FDA) announced that it had received reports of adverse reactions to over-the-counter liquid nutritional supplements marketed as Total Body Formula and Total Body Mega Formula (distributed by Total Body Essential Nutrition, Atlanta, Georgia) (1). A voluntary recall of these products was implemented. In May 2008, the FDA found substantially elevated selenium levels and modestly elevated chromium levels in the products (2).

Selenium nutrition of hybrid striped bass (Morone chrysops × M. saxatilis) bioavailability, toxicity and interaction with vitamin E

Two concurrent 12-week feeding trials were conducted to evaluate the bioavailability of inorganic sodium selenite and organic seleno-DL-methionine and to investigate the potential interaction between selenium and vitamin E in juvenile hybrid striped bass. In experiment 1, purified diets utilizing casein, gelatin and an amino acid premix as protein sources with a basal selenium concentration of 0.11 mg Se kg⁻¹ were supplemented with either Na₂SeO₃ to provide selenium concentrations of 1.19, 2.00, 5.17 and 21.23 mg Se kg⁻¹ or with seleno-DL-methionine to provide 0.90, 1.26 and 2.55 mg Se kg⁻¹ and fed to juvenile hybrid striped bass in aquaria. A second experiment evaluated potential interactions by feeding these purified diets with or without supplemental vitamin E or sodium selenite, singularly or in combination. No overt selenium deficiency signs were exhibited by fish in either of the experiments; however, signs of selenium toxicity including retarded weight gain (WG), reduced feed intake and feed efficiency ratio (FER) as well as increased mortality, were observed in fish fed the diet containing more than 20 mg Se kg⁻¹. Whole-body selenium and whole-body selenium retention were linearly influenced by sodium selenite and selenomethionine. However, there was no significant effect of dietary selenium, vitamin E or their interaction on WG, FER and survival. Slope-ratio analysis showed that bioavailability of seleno-DL-methionine as a selenium source for juvenile hybrid striped bass was significantly (P < 0.01) higher (3.3-fold) than sodium selenite.

The biogeochemistry of selenium in Sunan grassland, Gansu, Northwest China, casts doubt on the belief that Marco Polo reported selenosis for the first time in history

In order to clarify the historic academic problem of whether or not livestock poisoning in ancient Suzhou of Northwest China, recorded by Marco Polo in 1295, was selenosis, this study deals with the biogeochemistry of selenium in Sunan County in the Hexi Corridor, which is part of ancient Suzhou in China. It was found that quite a number of farm animals had suffered from intoxication and died as a result of grazing poisonous grasses, mostly Oxytropis DC, Stellera chamaejasme, and Achnatheru inebrians. Toxic symptoms of livestock grazing on Oxytropis DC are similar to those of selenium toxicity, for instance, hair loss and hoof lesions as described by Marco Polo. Therefore, we thought that toxic grass, probably Oxytropis DC, led to the intoxication of livestock recorded by Marco Polo. Average Se concentrations in two members of this species were 0.112 +/- 0.038 mg/kg for the root of Oxytropis glabra, 0.102 +/- 0.027 mg/kg for the stem and leaf of Oxytropis glabra, and 0.066 +/- 0.009 mg/kg for Oxytropis ochrocephala. The average soil selenium concentration was 0.205 +/- 0.127 mg/kg on grassland producing Oxytropis glabra and 0.152 +/- 0.024 mg/kg on grassland producing Oxytropis ochrocephala. The average Se concentration in other plants was 0.076 mg/kg in the root of Ephedra monosperma Mey, 0.029 mg/kg in the root of Rheum palmatum, 0.031 mg/kg in the root of Stellera chamaejasme, 0.037 mg/kg in Achnatherum inebrians, and 0.067 mg/kg in forage grass (Achnatherum splendens ohwi). Selenium concentrations in soils and plants in Sunan County are far less than the thresholds causing selenium toxicity in livestock. As a result, this study concludes that the livestock poisoning recorded by Marco Polo in 1295 might not have been selenosis.

Proteomic analysis of selenium embryotoxicity in cultured postimplantation rat embryos

Developmental toxicity of selenium (Se) is a nutritional, environmental and medicinal concern. Here, we investigated Se embryotoxicity by proteomic analysis of cultured rat embryos. Rat embryos at day 9.5 or 10.5 of gestation were cultured for 48 or 24 h, respectively, in the presence of sodium selenate (100 or 150 microM) or sodium selenite (20 or 30 microM). Proteins from the embryo proper and yolk sac membrane were analyzed by two-dimensional electrophoresis for quantitative changes from those in control embryos. Proteins with quantitative changes were identified by mass spectrometric analysis. Growth inhibition and morphological abnormalities of cultured embryos were observed in all the Se treatment groups. By the analysis of the embryo proper, actin-binding proteins were identified as proteins with quantitative changes by selenate: increased phosphorylated-cofilin 1, increased phosphorylated-destrin, decreased drebrin E, and decreased myosin light polypeptide 3. Many proteins showed similar changes between selenate and selenite, including increased ATP-synthase, decreased acidic ribosomal phosphoprotein P0, and decreased pyrroline-5-carboxylate reductase-like. In the yolk sac membrane, antioxidant proteins were identified for protein spots with quantitative changes by selenite: increased peroxiredoxin 1 and increased glutathione S-transferase. The identified proteins with quantitative changes by selenate or selenite were considered to be candidate proteins involved in Se embryotoxicity: the actin-binding proteins for selenate embryotoxicity, proteins with the similar changes for the common Se embryotoxicity and antioxidant proteins for modification of Se embryotoxicity by redox-related treatments. These proteins may also be used as biomarkers in developmental toxicity studies.