Bioaccumulation of waterborne selenium in the Asiatic clam Corbicula fluminea: influence of feeding-induced ventilatory activity and selenium species

A set of experiments was performed to investigate the bioavailability and the effect of Se on the ventilatory activity of the bivalve Corbicula fluminea, under different conditions of both algal cell densities and dissolved Se chemical forms and concentrations. A first set of experiments was conducted without selenium to investigate the changes in the ventilatory flow rate as a function of the concentration of the unicellular alga Chlamydomonas reinhardtii (10(5)-10(6) cells mL(-1)). For algal concentrations below 2-3x10(5) cells mL(-1), ventilatory activity was highly stimulated whereas it was independent of algal densities for higher values (up to 10(6) cells mL(-1)). To investigate the influence of this first ventilatory drive on selenium contamination process, bivalves were exposed to waterborne selenium at two different algal concentrations, selected to provide contrasting reference ventilatory activities. Three different selenium forms were studied [selenite Se(+IV), selenate Se(+VI) and selenomethionine SeMet] and were added into the water at concentrations of 50 and/or 500 microg L(-1). Each selenium form induced a specific behavioural response, an increase, a decrease or no change of ventilation being observed for Se(+IV), SeMet and Se(+VI), respectively. Selenium accumulation by the organisms was investigated at the organ level for the different exposure conditions. Selenomethionine was the most bioaccumulated form, followed by selenate and selenite, respectively. Despite the bivalves displaying different ventilatory behaviours at low or high algal density, there was no evidence showing reduction or enhancement of Se uptake in the chemical domain investigated.     

Studies on selenium-related compounds VI. Biosynthesis of dimethyl selenide in rat liver after oral administration of sodium selenate

Experiments were made to obtain data on the biological action of selenium in order to establish a standard for water quality for public water supply. Biosynthesis of dimethyl selenide in rat liver after oral administration of Na₂SeO₄ was investigated and the volatile selenium formed was identified. The study showed that dimethyl selenide, as a respiratory metabolite, was probably formed in the rat liver. Differences were noted as to dimethyl selenide formation from sodium selenite and sodium selenate in vitro. The test of single oral administration of sodium selenate indicated that dimethyl selenide formation increased progressively up to about 6 mg/kg and then reached a plateau at this dose. The increased accumulation of selenium in the liver after continuous oral administration was found to stimulate the methylation of selenium to dimethyl selenide. When sodium selenate was orally administered to rats, (CH₃)₂Se was found by TLC, GLC, and GC-mass spectrometry.     

Glutathione peroxidase activity in the selenium-treated alga Scenedesmus quadricauda

The function of selenium in an organism is mediated mostly by selenoproteins including glutathione peroxidase. Glutathione peroxidase is a potent anti-oxidative enzyme, scavenging a variety of peroxides. The green alga Scenedesmus quadricauda was used to investigate the relationship between the toxicity of selenium and the glutathione peroxidase activity. Selenium resistant strains SeIV and SeVI were synchronized and grown in high concentrations of Se (selenite or selenate). As a measure of selenium toxicity the EC(50) values were determined. During growth of the untreated wild type, glutathione peroxidase activity increased slightly and then declined gradually until the end of the cell cycle. A similar pattern was observed in untreated resistant strains and when resistant strains were grown in the presence of selenium in the oxidation state to which they were resistant. In the wild type cultivated with 50 mg Se L(-1) (selenite or selenate), activity increased to a high level and slowly declined until the end of the cell cycle. Similarly, activity increased in strains SeIV and SeVI when grown in the presence of selenium in the oxidation state to which they were not resistant. We followed the effect of selenium on the ultrastructure of S. quadricauda. After exposure to selenite, the chloroplast membranes of wild type were reorganized into thick bundles of thylakoids and the stroma became granulose. When selenate was added, the chloroplast of wild type had a fingerprint-like appearance, the stroma became less dense and starch production increased. In selenium resistant strains, when treated with the selenium form to which they were resistant, the chloroplast was affected, but not to such an extent as in the wild type. The activity of glutathione peroxidase in Scenedesmus was affected by selenium in an oxidation state-dependent manner. The most apparent effects of selenium on the ultrastructure involved impairment of the chloroplast and the overproduction of starch.     

Inhibition by selenium compounds of catecholamine secretion due to inhibition of Ca2+ influx in cultured bovine adrenal chromaffin cells

Selenium is an essential trace metal element, whereas large doses of selenium exert adverse effects to the human body. We examined the effects of selenium compounds, sodium selenite (Na2SeO3) and sodium selenate (Na2SeO4), on catecholamine secretion from cultured bovine adrenal chromaffin cells. Treatment of chromaffin cells with sodium selenite for 72, 48, and 24 h caused decreases in protein and catecholamine contents, in association with cell damage, at concentrations over 30, 300, and 300 microM, respectively. The cells treated with subtoxic conditions (<100 microM, 48 h) of sodium selenite were used for further experiments. Sodium selenite treatment for 48 h inhibited carbachol (CCh)-induced catecholamine secretion in a concentration-dependent and non-competitive manner, while it did not affect high K+- and veratridine-induced catecholamine secretion. Sodium selenite (100 microM) did not affect CCh- and veratridine-induced 22Na+ influx, while the compound inhibited 45Ca2+ influx induced only by CCh, but not high K+ and veratridine. Sodium selenate even at higher concentrations (1000 microM) did not affect any stimulus-induced catecholamine secretion and 45Ca2+ influx. Thus, sodium selenite may specifically exert adverse effects, such as inhibition of physiological stimulus-induced catecholamine secretion from adrenal chromaffin cells due to inhibition of Ca2+ influx.     

Toxicity of nutritionally available selenium compounds in primary and transformed hepatocytes

The essential trace element selenium is also toxic at low doses. Since supplementation of selenium is discussed as cancer prophylaxis, we investigated whether or not bioavailable selenium compounds are selectively toxic on malignant cells by comparing primary and transformed liver cells as to the extent and mode of cell death. Sodium selenite and selenate exclusively induced necrosis in a concentration-dependent manner in all cell types investigated. In primary murine hepatocytes, the EC50 was 20 microM for selenite, 270 microM for selenate, and 30 microM for Se-methionine. In the human carcinoma cell line HepG2, the EC50 for selenite was 40 microM, and for selenate 1.1 mM, whereas Se-methionine was essentially non-toxic up to 10 mM. Similar results were found in murine Hepa1-6 cells. Exposure of primary murine cells to selenate or selenite resulted in increased lipid peroxidation. Toxicity was inhibited by superoxide dismutase plus catalase, indicating an important role for reactive oxygen intermediates. In primary hepatocytes, metabolical depletion of intracellular ATP by the ketohexose tagatose, significantly decreased the cytotoxicity of Se-methionine, while the one of selenite was increased. These data do not provide any in vitro evidence that bioavailable selenium compounds induce preferentially apoptotic cell death or selectively kill transformed hepatocytes.     

Effect of selenate on growth and photosynthesis of Chlamydomonas reinhardtii

Algal communities play a crucial role in aquatic food webs by facilitating the transfer of dissolved inorganic selenium (both an essential trace element and a toxic compound for a wide variety of organisms) to higher trophic levels. The dominant inorganic chemical species of selenium in freshwaters are selenite (SeO(3)(2-)) and selenate (SeO(4)(2-)). At environmental concentrations, selenite is not likely to have direct toxic effects on phytoplankton growth [Morlon, H., Fortin, C., Floriani, M., Adam, C., Garnier-Laplace, J., Boudou, A., 2005a. Toxicity of selenite in the unicellular green alga Chlamydomonas reinharditii: comparison between effects at the population and sub-cellular level. Aquat. Toxicol. 73(1), 65-78]. The effects of selenate, on the other hand, are poorly documented. We studied the effects of selenate on Chlamydomonas reinhardtii growth (a common parameter in phytotoxicity tests). Growth inhibition (96-h IC(50)) was observed at 4.5+/-0.2 microM selenate (p<0.001), an effective concentration which is low compared to environmental concentrations. Growth inhibition at high selenium concentrations may result from impaired photosynthesis. This is why we also studied the effects of selenate on the photosynthetic process (not previously assessed in this species to our knowledge) as well as selenate's effects on cell ultrastructure. The observed ultrastructural damage (chloroplast alterations, loss of appressed domains) confirmed that chloroplasts are important targets in the mechanism of selenium toxicity. Furthermore, the inhibition of photosynthetic electron transport evaluated by chlorophyll fluorescence induction confirmed this hypothesis and demonstrated that selenate disrupts the photosynthetic electron chain. Compared to the classical 'growth inhibition' parameter used in phytotoxicity tests, cell diameter and operational photosynthetic yield were more sensitive and may be convenient tools for selenate toxicity assessment in non-target plants.     

Elemental selenium particles at nano-size (Nano-Se) are more toxic to Medaka (Oryzias latipes) as a consequence of hyper-accumulation of selenium: a comparison with sodium selenite

Recent studies have shown that elemental selenium particles at nano-size (Nano-Se) exhibited comparable bioavailability and less toxicity in mice and rats when compared to sodium selenite, selenomethinine and methylselenocysteine. However, little is known about the toxicity profile of Nano-Se in aquatic animals. In the present study, toxicities of Nano-Se and selenite in selenium-sufficient Medaka fish were compared. Selenium bioaccumulation and subsequent clearance in fish livers, gills, muscles and whole bodies were examined after 10 days of exposure to Nano-Se and selenite (100mug Se/L) and again after 7 days of depuration. Both forms of selenium exposure effectively increased selenium concentrations in the investigated tissues. Surprisingly, Nano-Se was found to be more hyper-accumulated in the liver compared to selenite with differences as high as sixfold. Selenium clearance of both Nano-Se and selenite occurred at similar ratios in whole bodies and muscles but was not rapidly cleared from livers and gills. Nano-Se exhibited strong toxicity for Medaka with an approximately fivefold difference in terms of LC(50) compared to selenite. Nano-Se also caused larger effects on oxidative stress, most likely due to more hyper-accumulation of selenium in liver. The present study suggests that toxicity of nanoparticles can largely vary between different species and concludes that the evaluation of nanotoxicology should be carried out on a case-by-case basis.     

Maternal selenium deficiency enhances the fetolethal toxicity of methyl mercury

The effect of maternal selenium deficiency on methyl mercury fetotoxicity was examined in the ICR strain of mice. Pregnant mice were fed either selenium-deficient diets based on torula yeast or selenium-supplemented diets which were identical to the former except that 0.1, 0.2, or 0.4 mg of selenium per kilogram of diet was added as sodium selenite. Fetolethality of methyl mercury was exacerbated by maternal selenium deficiency when mothers were administered sc 15, 25, or 35 mumol/kg/day of methylmercuric chloride (MMC) on the 13, 14, and 15th days of pregnancy. One-tenth part per million of selenium in the diet was sufficient to protect the fetuses against MMC fetolethality when dams were administered 25 mumol/kg/day of MMC. Mercury concentrations in maternal and fetal tissues were independent of the dietary selenium level. Selenium concentration and glutathione peroxidase (GSH-Px) activity in maternal tissues were unaffected by MMC administration. In fetal liver, on the other hand, selenium concentration was increased and GSH-Px activity was decreased concurrently by maternal MMC administration in the selenium-supplemented groups. Therefore, as far as GSH-Px activity was concerned, the bioavailability of selenium was markedly decreased in fetal liver by maternal injection of MMC. The increase in selenium content in fetal liver, which was observed only in the selenium-supplemented groups, may play an important role in protection against fetolethal toxicity of MMC.     

Availability and metabolism of 77Se-methylseleninic acid compared simultaneously with those of three related selenocompounds

Nutritional selenocompounds are considered to be transformed into the common intermediate selenide for utilization as selenoenzymes and/or for excretion as selenosugar and trimethylselenonium (TMSe). Therefore, selenocompounds can only be traced with a labeled selenium atom. Methylseleninic (MSA(IV)) has been proposed to be a third nutritional selenium source, the other two being inorganic selenocompounds and organic selenoamino acids, and to be a proximate selenochemical for producing the assumed biologically active form methylselenol. Here we applied a new tracer method to compare the availability and metabolism of MSA(IV) with those of three related selenocompounds under exactly identical host and tracing conditions. (82)Se-Selenite, (78)Se-selenate, (77)Se-MSA(IV) and (76)Se-methylselenonic acids (MSA(VI)) were simultaneously administered orally, each at the dose of 25 microg Se/kg body weight, to rats that had been depleted of endogenous natural abundance selenium with a single stable isotope ((80)Se). Time-related changes in the concentrations and/or distributions of the four labeled isotopes in the serum, liver, kidney, pancreas, lung and urine were determined simultaneously by inductively coupled argon plasma mass spectrometry (ICP MS) and/or HPLC-ICP MS. The availability with different isotope ratios was in the decreasing order of selenate>selenite=MSA(IV)>MSA(VI). Although selenate and MSA(VI) were distributed in organs and urine partly in their intact forms, MSA(IV) and selenite were not detected in the intact forms at all. MSA(IV) and MSA(VI) but not selenite or selenate produced TMSe in organs other than the liver, suggesting the transformation of MSA(IV) into methylselenol, and then either into selenide for the synthesis of selenoproteins and selenosugar or directly into TMSe. Thus, selenosugar and TMSe were produced widely in the organs. However, TMSe was not detected in the liver. The organ- and selenium source-specific production of TMSe was discussed as to the differences in selenium sources, and demethylation and methylation activity.     

Acute toxicity of inorganic selenium to Daphnia magna (Straus) and the effect of sub-acute exposure upon growth and reproduction

The acute toxicities of sodium selenite (Na₂SeO₃) and sodium selenate (Na₂SeO₄) to Daphnia magna were determined in defined culture at 22°C. For adults, the 48-h LC₅₀ values were 0.68 ppm selenium as selenite and 0.75 ppm selenium as selenate. Juveniles were more sensitive, with a 48-h LC₅₀ of 0.55 ppm selenium as selenate. Eggs and embryos were found to be much less sensitive, with a 72-h LC₅₀ of 1.4 ppm selenium as selenate.

Sub-acute exposure of D. magna to sodium selenate caused suppression of growth over instars 1–5 and reduced egg production in instar 9 when adults were exposed to test solutions from instar 6 onwards. These sublethal effects were found at concentrations in the range proposed as suitable for the use of selenium in the amelioration of mercury contamination.     

Dietary selenium reduces the formation of aberrant crypts in rats administered 3,2'-dimethyl-4-aminobiphenyl.

Human epidemiologic studies suggest that low selenium status is associated with increased cancer risk and that selenium supplementation is associated with reduction in the incidence of several cancers, including colorectal cancer. Aromatic and heterocyclic amine carcinogens are thought to be important in the etiology of human colorectal cancer, but no information is available on the effects of selenium on aromatic amine-induced colon cancer. In order to investigate this effect, aberrant crypt foci (ACF), the putative preneoplastic lesions of colon cancer in humans and rodents, were used as a biomarker to test the hypothesis that selenium supplementation can reduce aromatic amine-induced colon carcinogenesis. Male weanling F344 inbred rats were fed a basal torula yeast selenium-deficient diet supplemented with 0, 0.1, or 2. 0 mg selenium/kg diet as selenite, selenate, or selenomethionine (SeMet). Animals were fed the diets for 4 weeks and then administered 1 sc injection/week for 2 weeks of 3, 2'-dimethyl-4-aminobiphenyl (DMABP; 100 mg/kg) or vehicle (peanut oil). At 12 weeks, the rats were euthanized and the colon and rectum were removed, opened longitudinally, and fixed in 70% ethanol. Glutathione peroxidase activities in erythrocytes and liver cytosol and selenium concentrations in the colon/rectum and kidney increased significantly (p < 0.05) and in a dose-dependent manner with each of the three selenium diets. No ACF were identified in vehicle-treated rats. In DMABP-treated rats, ACF frequencies decreased significantly (p < 0.05) in groups supplemented with 0.1 or 2.0 mg selenium/kg diet as selenite and selenate but not SeMet. There were no significant differences in ACF and aberrant crypts between rats fed 0.1 vs 2.0 mg selenium/kg diet. These results suggest that dietary selenium, depending on chemical form, can reduce aromatic amine-induced colon carcinogenesis.     

Biomonitoring Equivalents for selenium

Selenium is an essential nutrient for human health with a narrow range between essentiality and toxicity. Selenium is incorporated into several proteins that perform important functions in the body. With insufficient selenium intake, the most notable effect is Keshan disease, an endemic cardiomyopathy in children. Conversely, excessive selenium intake can result in selenosis, manifested as brittle nails and hair and gastro-intestinal disorders. As such, guidance values have been established to protect against both insufficient and excessive selenium exposures. Dietary Reference Intakes (DRIs) have been established as standard reference values for nutritional adequacy in North America. To protect against selenosis resulting from exposure to excessive amounts of selenium, several government and non-governmental agencies have established a range of guidance values. Exposure to selenium is primarily through the diet, but monitoring selenium intake is difficult. Biomonitoring is a useful means of assessing and monitoring selenium status for both insufficient and excessive exposures. However, to be able to interpret selenium biomonitoring data, levels associated with both DRIs and toxicity guidance values are required. Biomonitoring Equivalents (BEs) were developed for selenium in whole blood, plasma and urine. The BEs associated with assuring adequate selenium intake (Estimated Average Requirements – EAR) are 100, 80 and 10 μg/L in whole blood, plasma and urine, respectively. The BEs associated with protection against selenosis range from 400 to 480 μg/L in whole blood, 180–230 μg/L in plasma, and 90–110 μg/L in urine. These BE values can be used by both regulatory agencies and public health officials to interpret selenium biomonitoring data in a health risk context.     

Modification of Chemical Toxicity by Selenium Deficiency

Modification of Chemical Toxicity by Selenium Deficiency. Burk,R.F. and Lane, J.M. (1983). Fundam. Appl. Toxicol. 3: 218–221.Selenium deficiency causes a number of hepatic metabolic alterationsin the rat which could lead to changes in chemical toxicity.It causes a decrease in glutathione peroxidase activity, anincrease in glutathione S-transferase activity, and an increasein the rate of glutathione synthesis. The hepatotoxicities ofthree compounds which bind to glutathione S-transferase; iodipamide,acetaminophen, and aflatoxin B₁, are decreased by selenium deficiency.The toxicity of redox cycling compounds is generally increasedby selenium deficiency and is accompanied by evidence of lipidperoxidation. Thus, nitrofurantoin (100 mg/kg) causes renaltubular necrosis in selenium-deficient rats but not in controls.Selenium-deficient rats are much more sensitive to diquat toxicitythan are controls. Lethality of diquat in selenium-deficientrats appears to be causally linked to lipid peroxidation. Lethalityof diquat in control rats is not linked to lipid peroxidation.The effect of selenium does not appear to be mediated by glutathioneperoxidase, however, indicating that selenium has another oxidantdefense function. Another interesting observation made was thatincreases in inspired O₂ tension decreased ethane production(lipid peroxidation) in selenium-deficient and in control ratsgiven diquat. Thus, O₂ appears to prevent diquat-induced lipidperoxidation.     

Hepatic glutathione metabolism and lipid peroxidation in response to excess dietary selenomethionine and selenite in mallard ducklings

Studies were conducted with mallard (Anas platyrhynchos) ducklings to determine the effects of excess dietary selenium (Se) on hepatic glutathione concentration and associated enzymes, and lipid peroxidation. Day-old ducklings were fed 0.1, 10, 20, or 40 ppm Se as seleno-DL-methionine or sodium selenite for 6 wk. Selenium from selenomethionine accumulated in a dose-dependent manner in the liver, resulting in a decrease in the concentration of hepatic-reduced glutathione (GSH) and total hepatic thiols (SH). These effects were accompanied by a dose-dependent increase in the ratio of oxidized glutathione (GSSG) to GSH, and an increase in malondialdehyde concentration as evidence of lipid peroxidation. Hepatic and plasma GSH peroxidase activity was initially elevated at 10 ppm Se as selenomethionine, whereas GSSG reductase activity was elevated at higher dietary concentrations of Se. Selenium from sodium selenite accumulated in the liver to an apparent maximum at 10 ppm in the diet, resulting in an increase in hepatic GSH and GSSG accompanied by a small decrease in total hepatic SH. Sodium selenite resulted in an increase in hepatic GSSG reductase activity at 10 ppm and in plasma GSSG reductase activity at 40 ppm. A small increase in lipid peroxidation occurred at 40 ppm. These findings indicate that excess dietary Se as selenomethionine has a more pronounced effect on hepatic glutathione metabolism and lipid peroxidation in ducklings than does selenite, which may be related to the pattern of accumulation. Effects of Se as selenite appear to be less pronounced in ducklings than reported in laboratory rodents. The effects of selenomethionine, which occurs in vegetation, are of particular interest with respect to the health of wild aquatic birds in seleniferous locations.     

Toxic effect of various selenium compounds on the rat in the early postnatal period

The toxic effect of selenium compounds (sodium selenate,d,l-selenomethionine,d,l-selenocystine, dimethyl selenide, and trimethylselenonium ion) was tested in 10-day old male rats. Increasing doses of the compounds were administered an s.c. injection and control animals were not injected. All compounds tested were lethal. Eye lens cataract was induced by the administration of selenate,d,l-selenomethionine, andd,l-selenocystine, while dimethyl selenide and trimethylselenonium ion failed to cause cataract. The cataractogenic effect of the above compounds may be attributed to their interference with glutathione metabolism.     

Effect of selenium on the uptake of methyl mercury across perfused gills of rainbow trout Oncorhynchus mykiss

The uptake of methyl mercury was measured across the perfused gills of rainbow trout Oncorhynchus mykiss. The effect of selenium, either in the blood (perfusion medium), or in the water was investigated. Methyl mercury was effectively taken up from the water across the gills into the perfusate. The uptake rate reached a stable level after 30 min perfusion. When the gills were placed in mercury free water after exposure to mercury in the water for 1 h, they continued to liberate significant amounts of accumulated mercury into the perfusate. Exposure to selenite (SeIV) or selenate (VI) (0.075–0.75 μM) in the external medium did not affect the uptake of methyl mercury across the gills or the liberation of the metal from the gills. Internal selenite or selenate (7.5 μM) augmented the uptake of methyl mercury across the gills and internal selenite also increased the amounts of liberated methyl mercury from the gills in the unload period. Internal selenium, increased the mercury accumulation in the gills, whereas, external selenium did not alter the mercury accumulation in the gills. Uptake of selenium from the water across the gills occurred very slowly.     

Embryotoxicity and dose-response relationships of selenium in hamsters

Pregnant hamsters were treated with selenite, selenate, and selenomethionine during the critical stages of embryogenesis. The dosing regimens were oral, intravenous, and osmotic minipump infusion. Malformations, mainly encephaloceles, were noted with oral and intravenous selenite and selenate but were associated with maternal toxicity manifested by inanition and weight loss. Fetal body weights and lengths were reduced in a dose-dependent manner with the inorganic forms. Single oral doses of selenomethionine above 77 mumol/kg induced similar malformations but not when the dose was delivered orally over four days nor by minipump over several days. Fetal body weights and lengths were decreased by selenomethionine in a dose-dependent manner. Maternal toxicity was pronounced with the higher doses of selenomethionine. Assigning a specific teratogenic effect to selenium is confounded by maternal toxicity.     

Selenium compounds modulate the calcium release channel/ryanodine receptor of rabbit skeletal muscle by oxidizing functional thiols

Selenium compounds, such as sodium selenite and Ebselen were shown to increase high affinity ryanodine binding to the skeletal muscle type ryanodine receptor (RyR1) at nanomolar concentrations, and inhibit the receptor at low micromolar concentrations. This biphasic response was observed in both concentration and time-dependent assays. Extensive washing did not reverse either the stimulation or suppression of receptor binding, but both were prevented or reversed by addition of reduced glutathione, GSH. Selenium compounds were also shown to induce Ca(2+) release from the isolated sarcoplasmic reticulum vesicles. Sodium selenite and Ebselen stimulated the skeletal muscle ryanodine receptor by oxidizing 14 of 47 free thiols per monomer on RyR1 (as detected with the alkylating agent 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin) (CPM). Oxidation of the remaining thiols by these selenium compounds resulted in inhibition of the ryanodine receptor.     

Effect of dietary selenium on the metabolism of aflatoxin B1 in turkeys

To investigate the biochemical mechanism of the previously reported protective effect of dietary selenium against aflatoxin toxicity, the hepatic metabolism of aflatoxin B1 in turkey poults was examined at various dietary selenium concentrations. Diets were supplemented with 0.2, 2.0 or 4.0 ppm selenium (as sodium selenite) and 500 ng aflatoxin B1/g diet in an 18-day trial. Free and conjugated aflatoxin and metabolites were quantified using high-performance liquid chromatography. The proportion of liver aflatoxins in conjugated forms increased and the ratio of free aflatoxin B1/M1 decreased with increasing dietary selenium concentrations. These in vivo results provide evidence of selenium-induced enhancement of aflatoxin detoxification processes. In a similar experiment using 2.0 ppm selenium and 750 ng aflatoxin B1/g diet, the concentration of hepatic reduced glutathione, cytochrome P-450 and the activity of enzymes involved in the metabolism of aflatoxin B1 and glutathione were determined. Although the selenium supplement increased glutathione peroxidase activity, dietary selenium had no effect on reduced glutathione or cytochrome P-450 concentrations or on the activities of glutathione transferase E, glucuronyl transferase and cytochrome c reductase. These data indicate that the protective action of selenium is not mediated by an increase in glutathione availability for aflatoxin conjugation or by effects on the activities of these enzymes as measured in vitro.     

Effects of selenium on toxicity and ultrastructural localization of mercury in cultured murine macrophages

The effects of selenium on cellular toxicity and histochemical distribution of mercury were examined in a cell culture system of mouse peritoneal macrophages. Selenium protected against the toxicity of mercury in cultures exposed to 4 microM of mercuric chloride. Selenomethionine caused a significant increase in cell survival throughout the experiments, while sodium selenite delayed the toxicity of mercury for a while, after which selenite itself had a toxic effect. The amount of mercury visualized by autometallography was increased in macrophage cultures pre-exposed to sodium selenite or selenomethionine. The additional mercury made visible by this histochemical demonstration was located in the cytoplasm as well as in the lysosomes.