Gender-dependent effects of selenite on the perfused rat heart

Gender differences are related to the manner in which the heart responds to chronic and acute stress conditions of physiological and pathological nature. Depending on dose, sodium selenite acts as an antioxidant proven to have beneficial effects in several pathological conditions G. Drasch, J. Schopfer, and G. N. Schrauzer, Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and non-smokers, and relevance to the cancer protective effects of selenium,Biol. Trace Element Res. 103(2), 103–107 (2005); R. G. Kasseroller and G. N. Schrauzer, Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review,Am. J. Ther. 7(4), 273–279 (2000); G. N. Schrauzer, Anticarcinogenic effects of selenium,Cell. Mol. Life Sci. 57(13–14), 1864–1873 (2000); I. S. Palmer and O. E. Olson, Relative toxicities of selenite and selenate in the drinking water of rats,J. Nutr. 104(3), 306–314 (1974). To date, little is known about the gender-dependent direct effects of toxic doses of selenite on electrophysiology of the cardiovascular system H. A. Schroeder and M. Mitchener, Selenium and tellurium in rats: effect on growth, survival and tumors,J. Nutr. 101(11), 1531–1540 (1971); G. N. Schrauzer, The nutritional significance, metabolism and toxicology of selenomethionine,Adv. Food Nutr. Res. 47, 73–112 (2003). In the present study, the effects of in vitro toxic concentrations of sodium selenite ranging from 10^-6 M to 10^-3 M were tested on both male and female rat heart preparations. The toxic effects seen in an electrocardiogram and left ventricular pressure were dose and sex dependent at most of the tested concentrations. The present study clearly shows that at toxic doses, stress conditions are induced by selenite, resulting in gender-dependent modifications of the heart function. This modification is more pronounced in the contraction cascade of female rats. Males, on the other hand, had been much more affected in excitation-related parameters.     

Biochemical and morphological characteristics of selenite-induced apoptosis in human hepatoma hep G2 cells

Selenium is a cellular growth inhibitor in many mammary tumor cells. To comprehend the mechanism for the selenium-induced cell death, we examined the effects of sodium selenite, which has been one of the most extensively investigated selenium compounds, in human hepatoma Hep G2 cells. Cell viability gradually decreased after treatment with sodium selenite within the concentration range of 10–50 μM. Low (10 μM) selenite has shown a high-percentage laddering pattern compared to the high (25 μM) cytotoxic selenium concentration in agarose gel electrophoresis. G₂M-phase enrichment was also concentration dependent. The most consistent transmission electron microscopic finding was the existence of large lysosomes. Based on these data, we hypothesize that sodium selenite predominantly shows its apoptotic effect over hydrogen selenite accumulation.     

Bioeffects of selenite on the growth of Spirulina platensis and its biotransformation

The bioeffects of selenium on the growth of Spirulina platensis and the selenium distribution were investigated. S. platensis was batch cultured in Zarrouk medium containing increasing concentrations of sodium selenite. The biotransformation characteristic of selenium was analysed by the determination of the detailed selenium distribution forms. At 35 degrees C, 315.2 microEm(-2) x s(-1), sodium selenite concentrations below 400 mg x l(-1) were found to stimulate algal growth, especially in the range of 0.5-40 mg x l(-1). However, above 500 mg x l(-1) sodium selenite was toxic to this alga with the toxicity being related to the sulfite level in the medium. S. platensis was found to resist higher selenite by reducing toxic Se(IV) to nonsoluble Se(0). Selenium was accumulated efficiently in S. platensis during cultivation with accumulated selenium increasing with selenite concentration in the medium. It was demonstrated that inorganic selenite could be transformed into organic forms through binding with protein, lipids and polysaccharides and other cell components. The organic selenium accounted for 85.1% of the total accumulated selenium and was comprised of 25.2% water-soluble protein-bound, 10.6% lipids-bound and 2.1% polysaccharides-bound selenium. Among the organic fractions lipid possessed the strongest ability to accumulate Se (6.47 mg x kg(-1)). The 14.9% inorganic selenium in S. platensis was composed of Se(IV) (13.7%) and Se(VI) (1.2%).     

Promotion of lipid oxidation by selenate and selenite and indicators of lipid peroxidation in the rat

The AIN-93 reformulation of the AIN-76A rodent diet includes a change in selenium supplement from sodium selenite to sodium selenate to reduce dietary lipid peroxidation. A change to selenate as the standard form of Se in rat diets would render results from previous work using selenite less relevant for comparison with studies using the AIN-93 formulation. To critically examine the rationale for the AIN-93 recommendation, we prepared Torula yeast basal diets patterned as closely as possible after the AIN-93 formulation and supplemented with 0, 0.15 (adequate), or 2.0 (high) mg selenium/kg diet as sodium selenite or sodium selenate. Livers isolated from male Sprague-Dawley rats fed these diets for 15 wk showed no differences in thiobarbituric acid-reactive substances or lipid hydroperoxides measured with the ferrous oxidation in xylenol orange method. Lipids isolated from samples of high-selenate and high-selenite diets showed no differences in conjugated dienes. The addition of selenate or selenite to soybean oil did not result in an altered Oil Stability Index. These results demonstrate that selenate is not less likely than selenite to cause oxidation of other dietary components. Benefits of selenate over selenite in the diets of rodents remain to be demonstrated. Results included in this paper were presented at the meeting of Experimental Biology 98, San Francisco, CA, April 18–22, 1998, and published in abstract form (Moak, M. A., Johnson, B. L., & Christensen, M. J. [1998] On the AIN-93G recommendation for selenium. FASEB J. 12, A824).     

还原亚硒酸盐产生红色单质硒光合细菌菌株的筛选与鉴定

从实验室保藏的光合细菌中筛选出一株对亚硒酸钠还原效率较高的菌株S3,其亚硒酸钠还原产物通过透射电子显微镜及EDX(Electron-Dispersive X-ray)分析确定为红色单质硒。菌株S3的形态学特征、生理生化特征及光合色素扫描结果与固氮红细菌(Rhodobacter azotoformans)的特征基本一致;16S rDNA序列(GenBank登录号为DQ402051)在系统发育树中与固氮红细菌同属一个类群,序列同源性为99%。根据上述结果将菌株S3鉴定为固氮红细菌。初步研究了该菌株还原亚硒酸钠的特性,首次报道固氮红细菌具有还原亚硒酸盐产生红色单质硒的能力,为今后利用微生物方法治理环境中硒污染、利用微生物方法获得活性红色单质硒以及对微生物还原亚硒酸盐产生红色单质硒的机理研究奠定了良好的基础。     

Selenium homeostasis and induction of thioredoxin reductase during long term selenite supplementation in the rat

Selenium is a candidate treatment for liver tumour prevention in chronic liver disease. In this study, we have studied selenium uptake, distribution and accumulation in rats provided with water containing tumour-preventive doses of sodium selenite for 10 weeks. Male Fischer 344 rats were given drinking water containing 1 μg/mL or 5 μg/mL sodium selenite. Selenium levels were monitored in serum and liver tissue over the 10-week period, and the kinetics of induction of the redox-active cytosolic selenoenzyme thioredoxin reductase were followed. Selenite exposure via drinking water caused a dose-dependent increase in blood and liver selenium levels, with plateaus at 6 and 8 weeks, respectively. These plateaus were reached at the same level of selenium regardless of dose, and no further accumulation was observed. A selenium-dependent increase in the activity of TrxR1 in parallel with the increase in liver selenium levels was also seen, and the induction of TrxR1 mRNA was seen only during the first three days of treatment, when the levels of selenium in the liver were increasing. Sodium selenite at 1 and 5 μg/mL did not affect body weight or relative liver mass. We concluded that long-term treatment with selenite did not cause accumulation of selenium and that the activity of TrxR1 in the liver rose with the selenium levels. We therefore suggest that sodium selenite at doses up to 5 μg/mL could be used for long-term tumour prevention.     

细菌还原氧化态硒产生红色单质硒的研究进展

硒是一种生命必需的微量元素,但高浓度时毒性较强且会造成环境污染。许多细菌可以将亚硒酸盐(SeO32-)或硒酸盐(SeO42-)等毒性较高的氧化态硒还原为毒性较小的红色单质硒(Se°),形成硒-蛋白复合物,它们对于获得最佳补硒方式和治理硒环境污染具有应用潜力。近年来,关于这一生物还原过程,人们进行了大量的研究,包括碳源、氧气、元素硫、谷胱甘肽以及一些氧化还原酶和膜转运蛋白等在内的多种物质都被发现可能影响或参与了细菌对硒的代谢。综述了细菌进行生物还原氧化态硒的影响因素及不同细菌产生红色单质硒机理的研究进展。     

Effect of fertilization on selenium content of tea and the nutritional function of Se-enriched tea in rats

The present study examined the effect of fertilization with sodium selenite on the selenium content of tea and the nutritional function of Se-enriched tea. Selenium content of tea leaves was increased up to 0.36 g g^–1 by the application of sodium selenite to soil at 0.5 and 1.0 kg Se ha^–1. Application by a Se-enriched organic manure at a rate of 0.5 kg Se ha^–1 provided a higher biological availability of selenium for plant uptake compared with a similar amount of sodium selenite. Foliar spray of sodium selenite at 50–100 g Se ha^–1 increased the selenium content to 0.32–1.45 g g^–1 in tea leaves sampled at the 8–26 days after spraying. Selenium content in the blood and liver, glutathione peroxidase activity in blood of rats were significantly enhanced by feeding of an extracted solution of Se-enriched tea leaves and sodium selenite. Glutathione peroxidase activity in liver of rats fed with Se-enriched tea was higher than that fed with sodium selenite, indicating that the selenium in Se-enriched tea leaves is a more effective Se source than sodium selenite. Increasing the Se level in food products through the application of a selenium fertilizer is a safe, effective and feasible means of increasing the selenium intake of human and animals in low selenium areas of China.     

Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion.

Glutathione peroxidase and thioredoxin reductase are selenocysteine-dependent enzymes that protect against oxidative injury. This study examined the effects of dietary selenium on the activity of these two enzymes in rats, and investigated the ability of selenium to modulate myocardial function post ischemia-reperfusion. Male wistar rats were fed diets containing 0, 50, 240 and 1000 microg/kg sodium selenite for 5 weeks. Langendorff perfused hearts isolated from these rats were subjected to 22.5 min global ischemia and 45 min reperfusion, with functional recovery assessed. Liver samples were collected at the time of sacrifice, and heart and liver tissues assayed for thioredoxin reductase and glutathione peroxidase activity. Selenium deficiency reduced the activity of both glutathione peroxidase and thioredoxin reductase systemically. Hearts from selenium deficient animals were more susceptible to ischemia-reperfusion injury when compared to normal controls (38% recovery of rate pressure product (RPP) vs. 47% recovery of RPP). Selenium supplementation increased the endogenous activity of thioredoxin reductase and glutathione peroxidase and resulted in improved recovery of cardiac function post ischemia reperfusion (57% recovery of RPP). Endogenous activity of glutathione peroxidase and thioredoxin reductase is dependent on an adequate supply of the micronutrient selenium. Reduced activity of these antioxidant enzymes is associated with significant reductions in myocardial function post ischemia-reperfusion.     

Use of an antiarrhythmic drug against acute selenium toxicity

ObjectiveSelenium is an essential trace element. But, selenium may have toxic effects in high doses. There are no proven antidotes or curative treatments for acut selenium toxicity. Treatment involves stopping the exposure and providing supportive care for symptoms. Therefore, it is necessary to find more effective substances in the treatment of selenium toxicity. The aim of this study was to increase the survival rate of animals by supporting the heart with amiodarone and to determine the effect of amiodarone on the pathological, hematological and biochemical parameters in acute selenium intoxication.Methods64 Wistar-Albino rats were divided into four groups. Group I was given only distilled water, Group II was given 18 mg/kg dose of amiodarone, Group III was given 18 mg/kg amiodarone and 10 mg/kg sodium selenite and Group IV was given sodium selenite 10 mg/kg (LD₅₀ dose)orally.Results11 of the 16 animals in Group IV died within the first 48 h of drug administration. However, no deaths were observed in the rats in Group III. No hematological changes were observed. Biochemically, CK, CK-MB and LDH levels of Group IV were higher than the other groups on both the 2nd and 10th days. In Groups II and III, this serum level decreased, and vitamin B12 levels increased. In macroscopic inspections of the organs of Groups III and IV, slight paleness was detected. Histopathologically, degenerative changes in tissue were observed, especially in Group IV.ConclusionThis study shows that amiodarone application has a reducing effect on selenium toxicity. This was because amiodarone protected the heart by reducing CK and CK-MB levels and increased vitamin B12 levels, which play a role in the synthesis of S-adenosyl methionine that converts selenium into a nontoxic form.     

Extracellular production of hydrogen selenide accounts for thiol-assisted toxicity of selenite against Saccharomyces cerevisiae

Administration of selenium in humans has anticarcinogenic effects. However, the boundary between cancer-protecting and toxic levels of selenium is extremely narrow. The mechanisms of selenium toxicity need to be fully understood. In Saccharomyces cerevisiae, selenite in the millimolar range is well tolerated by cells. Here we show that the lethal dose of selenite is reduced to the micromolar range by the presence of thiols in the growth medium. Glutathione and selenite spontaneously react to produce several selenium-containing compounds (selenodiglutathione, glutathioselenol, hydrogen selenide, and elemental selenium) as well as reactive oxygen species. We studied which compounds in the reaction pathway between glutathione and sodium selenite are responsible for this toxicity. Involvement of selenodiglutathione, elemental selenium, or reactive oxygen species could be ruled out. In contrast, extracellular formation of hydrogen selenide can fully explain the exacerbation of selenite toxicity by thiols. Indeed, direct production of hydrogen selenide with D-cysteine desulfhydrase induces high mortality. Selenium uptake by S. cerevisiae is considerably enhanced in the presence of external thiols, most likely through internalization of hydrogen selenide. Finally, we discuss the possibility that selenium exerts its toxicity through consumption of intracellular reduced glutathione, thus leading to severe oxidative stress.     

Supplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats

Selenium is an essential micronutrient mineral found mainly in soils and has been shown to prevent certain cancers in humans and animals. However, the dose and effects of selenium on liver cancer are controversial. The aim of this study was to investigate the effects of sodium selenite (4 mg/kg in drinking water) on chemically induced hepatocarcinogenesis in rats. Hepatocarcinogenesis was induced by a single intraperitoneal injection of diethyl nitrosamine (DEN) (200 mg/kg body weight) and 2 weeks later, the carcinogenic effect was promoted by 2-acetylaminofluorene (2-AAF) (0.02%). 44 Sprague-Dawley rats were divided into 6 groups: negative control, positive control (DEN+2-AAF), pre-selenium group (sodium selenite for 4 weeks, then DEN+2-AAF), pre-selenium control group (sodium selenite for 4 weeks, no DEN or 2-AAF), post-selenium group (sodium selenite for 8 weeks after 4 weeks of DEN injection) and post-selenium control group (sodium selenite for 8 weeks, no DEN or 2-AAF). Hematoxylin and eosin plus Gordon and Sweet’s methods were used to stain liver tissues. The results showed that the number and sizes of hepatic nodules in pre- and post-selenium treatment groups significantly decreased (P<0.05) compared with the positive control. Microscopic analysis of pre- and post-selenium groups showed that the majority of nodules were hyperplastic with preserved liver architecture, whereas the positive control was full of neoplastic nodules with a completely disrupted liver architecture. Hence, pre- and post-selenium treatments can reduce the extent of liver cancer on chemically induced hepatocarcinogenesis in rats.     

Efficient Preparation of Selenium/Glutathione-Enriched Candida utilis and Its Biological Effects on Rats

The main purpose of this study was to prepare selenium/glutathione-enriched Candida utilis and investigate its effect on growth performance, antioxidant capacity, and immune response in rats. The preparation of the selenium/glutathione-enriched yeast was conducted using fed-batch culture for high cell density. The optimal culture conditions for increased intracellular organic selenium and glutathione contents were as follows: the concentrated medium was fed beginning at 12?h using a polynomial feeding strategy until a total glucose concentration of 150?g/l was reached, and sodium selenite was continuously added together with glucose to a total concentration of 60?mg/l. As a result, 81?% of sodium selenite was assimilated and transformed into organic selenium by C. utilis under optimal conditions, which in turn resulted in greater glutathione accumulation and lower malondialdehyde cellular content in the yeast. To investigate and compare the effects of the prepared selenized C. utilis and other dietary supplements, 40 female rats were divided into five groups of eight rats each, following a randomized block design. Experimental feeding was conducted for a period of 6?weeks. Selenium supplementation with inorganic selenium (sodium selenite) and organic selenium (selenized C. utilis) showed better results than the control and other groups supplemented with yeast with or without glutathione. The body mass of rats, selenium deposition, and oxidative enzymes activities in both serum and liver samples, and immunity responses were all significantly improved by selenium supplementation, and between the two sources, organic selenium was more effective than inorganic selenium.     

The antimutagenic effect of selenium on 7,12-dimethylbenz(a)anthracene and metabolites in the amesSalmonella/microsome system

The antimutagenic effect of selenium as sodium selenite, sodium selenate, selenium dioxide, and seleno-methionine was studied in the AmesSalmonella/microsome mutagenicity test using 7,12-dimethylbenz(a)anthracene (DMBA) and some of its metabolites. Selenium (20 ppm) as sodium selenite reduced the number of histidine revertants on plates containing up to 100 μg DMBA/plate. Increasing concentrations of selenium as sodium selenite, sodium selenate, and selenium dioxide up to 40 ppm Se progressively decreased the number of revertants caused by 50 μg DMBA. DMBA and its metabolites 7-hydroxymethyl-12-methylbenz(a)anthracene, 12-hydroxymethyl-7-methylbenz(a)anthracene, and 3-hydroxy-7,12-dimethylbenz(a)anthracene were mutagenic forSalmonella typhimurium TA100 in the presence of an S-9 mixture. Selenium supplementation as Na₂SeO₃ reduced the number of revertants induced by these metabolites to background levels. The antimutagenic effect of inorganic selenium compounds cannot be explained by toxicity of selenium as determined by viability tests withSalmonella typhimurium TA100. Selenium supplementation in all forms examined, except sodium selenate, decreased the rate of spontaneous reversion. Selenium as sodium selenate was slightly mutagenic at concentrations of 4 ppm or less. Higher concentration of Na₂SeO₄ inhibited the mutagenicity of DMBA. The present studies support the anticarcinogenic potential of selenium and indicate that form and concentration are important factors in this trace element's efficacy.     

Variation in selenium tolerance and accumulation among 19 Arabidopsis thaliana accessions

Selenium (Se) is an essential element for many organisms but also toxic at higher levels. The objective of this study was to identify accessions from the model species Arabidopsis thaliana that differ in Se tolerance and accumulation. Nineteen Arabidopsis accessions were grown from seed on agar medium with or without selenate (50 microM) or selenite (20 microM), followed by analysis of Se tolerance and accumulation. Tissue sulfur levels were also compared. The Se Tolerance Index (root length+Se/root length control) varied among the accessions from 0.11 to 0.44 for selenite and from 0.05 to 0.24 for selenate. When treated with selenite, the accessions differed by two-fold in shoot Se concentration (up to 250 mgkg(-1)) and three-fold in root Se concentration (up to 1000 mgkg(-1)). Selenium accumulation from selenate varied 1.7-fold in shoot (up to 1000 mgkg(-1)) and two-fold in root (up to 650 mgkg(-1)). Across all accessions, a strong correlation was observed between Se and S concentration in both shoot and root under selenate treatment, and in roots of selenite-treated plants. Shoot Se accumulation from selenate and selenite were also correlated. There was no correlation between Se tolerance and accumulation, either for selenate or selenite. The F(1) offspring from a cross between the extreme selenate-sensitive Dijon G and the extreme selenate-tolerant Estland accessions showed intermediate selenate tolerance. In contrast, the F(1) offspring from a cross between selenite-sensitive and -tolerant accessions (Dijon GxCol-PRL) were selenite tolerant. The results from this study give new insight into the mechanisms of plant selenium (Se) tolerance and accumulation, which may help develop better plants for selenium phytoremediation or as fortified foods.     

Vicia root-mirconucleus and sister chromatid exchange assays on the genotoxicity of selenium compounds

Selenium (Se) is an important metalloid with industrial, environmental, biological and toxicological significance. Excessive selenium in soil and water may contribute to environmental selenium pollution, and affect plant growth and human health. By using Vicia faba micronucleus (MN) and sister chromatid exchange (SCE) tests, possible genotoxicity of sodium selenite and sodium biselenite was evaluated in this study. The results showed that sodium selenite, at concentrations from 0.01 to 10.0mg/L, induced a 1.9-3.9-fold increase in MN frequency and a 1.5-1.6-fold increase in SCE frequency, with a statistically significantly difference from the control (P<0.05 and 0.01, respectively). Sodium selenite also caused mitotic delay and a 15-80% decrease in mitotic indices (MI), but at the lowest concentration (0.005mg/L), it slightly stimulated mitotic activity. Similarly, the frequencies of MN and SCE also increased significantly in sodium biselenite treated samples, with MI decline only at relatively higher effective concentrations. Results of the present study suggest that selenite is genotoxic to V. faba root cells and may be a genotoxic risk to human health.     

The Effect of Different Levels of Selenium in Mineral Mixtures and Salt Licks on Selenium Status in Sheep

This paper describes 3 experiments comparing the effect of 10, 25 and 40 mg Se/kg, as sodium selenite, in mineral mixtures and salt licks fed to sheep. The supplement was given during the indoor season from October to May to 7 different flocks, each consisting of 50 to 100 sheep, in areas with selenium deficiency problems. The average selenium level in the basic diets did not exceed 0.05 mg/kg. Selenium status was monitored in the blood of ewes and lambs, and in milk. Blood selenium in lambs correlated well with blood selenium in their dams (r = 0.85). Selenium levels in milk on day 1 (colostrum) correlated well with selenium levels in dams (r = 0.92) and in offspring (r = 0.87). Statistically significant differences were found between the different flocks. In areas with extreme selenium deficiency, 10 mg Se/kg in mineral mixtures and salt licks proved insufficient. A content of 25 mg Se/kg, providing a daily intake of about 0.4 mg selenium, resulted in selenium levels in ewes’ blood, ewes’ milk and in the offspring that should prevent selenium deficiency disease without causing any toxic effects.     

Influence of selenium on mercuric chloride cellular uptake and toxicity indicating protection: studies on cultured K-562 cells

Selenium and mercuric chloride (MC) interactions regarding cellular uptake and selenium protection on MC toxicity have been studied. Human K-562 cells were pretreated or simultaneously treated with either selenite (5 or 50 microM) or selenomethionine (10 or 50 microM) together with MC (35 or 50 microM). Both treatments with selenite showed an increase of mercury uptake with increased selenium dose. In the pretreated or simultaneously treated selenite and 35 microM MC combinations, no inhibition of growth was seen, whereas all 50-microM MC combinations were toxic to the cells. A selenite-dependent protection was obtained for both exposure protocols when considering the cellular uptake of mercury. The cells died when the accumulation on d 4 reached more than about 0.8 x 10(-15) mol/cell of mercury, whereas they survived up to twofold more mercury uptake when exposed to selenite. Selenomethionine gave, with a few exceptions, similar effects as selenite on MC uptake and toxicity.     

Toxicity of selenium to Lemna minor in relation to sulfate concentration

The aquatic plant Lemna minor L. was treated with sodium selenite or sodium selenate to test the toxicity of these salts in relation to high or low levels of sulfate in the culture medium. Several morphophysiological aspects, such as multiplication rate (MR), ratio of the number of fronds to number of colonies (Nfr/Ncol), frond size, cell ultrastructure, pigment content and guaiacol peroxidase (EC 1.11.1.7) activity were evaluated. Their variations might be an indirect means of evaluating the degree of susceptibility or tolerance of this plant to selenium (Se). Sodium selenite or sodium selenate treatments at concentrations ranging from 1 to 256 μ M generally decreased the investigated parameters. Moreover, the sulfate concentration influenced the toxicity of both Se salts. In general, with treatments in a medium containing a high sulfate (HS) content, sodium selenite appeared more toxic than sodium selenate, whereas in a low sulfate (LS) medium, sodium selenate seemed more toxic. MR was significantly increased at 1–4 μ M selenite and LS or 8 μ M selenate and HS levels, suggesting that Se may be an essential nutrient for this plant.