富硒酵母中硒赋态的研究

硒是人体必需的一种微量元素,参与合成硒代半胱氨酸、硒代甲硫氨酸以及多种硒代蛋白(酶),具有抗肿瘤、抗氧化、增强人体免疫等多种生物学活性,与人体的健康有着密切关系.硒以不同的形式存在于自然界中,大致可分为无机硒和有机硒两种,其生物活性与毒性也各有不同.富硒酵母作为补充硒元素的主要形式之一,具有生物利用度高、食用安全、毒性低等优点.研究富硒酵母中的硒的赋态,对合理摄取硒元素,促进人体健康具有重要意义,因此成为近年来研究的热点.     

硒的生物学功能及其补充剂的研究现状

硒是人体必需的、只能外源性补充的微量元素之一,人体缺硒可以导致癌症和多种疾病。本文阐述了硒的抗肿瘤、防衰老、抗氧化和增强机体免疫力等多种生物学功能,并概述了硒补充剂的研究现状,进而对硒补充剂的开发进行了展望。     

Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice

Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through which selenium exerts powerful antioxidant effects. Selenium also elicits pro-oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or bioavailability and toxicity, of selenium depend on its chemical form. Selenomethionine is considered to be the most appropriate supplemental form due to its excellent bioavailability and lower toxicity compared to various selenium compounds. The present studies reveal that, compared with selenomethionine, elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase but has much lower toxicity as indicated by median lethal dose, acute liver injury, and short-term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with reduced risk of selenium toxicity.     

Selenium interactions and toxicity: a review

Selenium is an essential trace element for mammals. Through selenoproteins, this mineral participates in various biological processes such as antioxidant defence, thyroid hormone production, and immune responses. Some reports indicate that a human organism deficient in selenium may be prone to certain diseases. Adverse health effects following selenium overexposure, although very rare, have been found in animals and people. Contrary to selenium, arsenic and cadmium are regarded as toxic elements. Both are environmental and industrial pollutants, and exposure to excessive amounts of arsenic or cadmium can pose a threat to many people’s health, especially those living in polluted regions. Two other elements, vanadium and chromium(III) in trace amounts are believed to play essential physiological functions in mammals. This review summarizes recent studies on selenium interactions with arsenic and cadmium and selenium interactions with vanadium and chromium in mammals. Human studies have demonstrated that selenium may reduce arsenic accumulation in the organism and protect against arsenic-related skin lesions. Selenium was found to antagonise the prooxidant and genotoxic effects of arsenic in rodents and cell cultures. Also, studies on selenium effects against oxidative stress induced by cadmium in various animal tissues produced promising results. Reports suggest that selenium protection against toxicity of arsenic and cadmium is mediated via sequestration of these elements into biologically inert conjugates. Selenium-dependent antioxidant enzymes probably play a secondary role in arsenic and cadmium detoxification. So far, few studies have evaluated selenium effects on chromium(III) and vanadium actions in mammals. Still, they show that selenium may interact with these minerals. Taken together, the recent findings regarding selenium interaction with other elements extend our understanding of selenium biological functions and highlight selenium as a potential countermeasure against toxicity induced by arsenic and cadmium.     

Influence of selenium sources on age-related and mild heat stress-related changes of blood and liver glutathione redox cycle in broiler chickens (Gallus domesticus)

Selenium is an essential trace element that up-regulates a major component of the antioxidant defense mechanism by controlling the body's glutathione (GSH) pool and its major Se-containing antioxidant enzyme, glutathione peroxidase (GPX). Evidence has emerged suggesting that organic selenium, natural seleno-amino acids found in plants, grains and selenized yeast, maintains the antioxidant defense system more efficiently than inorganic selenium. Inorganic selenium is a pro-oxidant, whereas organic selenium possesses antioxidant properties itself. As a pro-oxidant, inorganic selenium is not suitable for animals or humans. Therefore, we examined the GSH–GPX system in broiler chickens and determined that organic selenium was indeed more beneficial than inorganic selenium. Chickens fed the organic selenium as Sel-Plex^®, a selenized yeast, had elevated GPX activity in both blood and liver in a thermoneutral environment and after heat distress. More importantly, the ability to reduce the oxidized glutathione (GSSG to 2 GSH) was enhanced and facilitated by maintenance of glutathione reductase activity. Organic selenium-fed chickens were less affected by mild heat distress than inorganic selenium-fed chickens, and this assessment was based upon less induction of heat shock protein 70 (hsp70) in organic selenium-fed chickens. Our results clearly show that heat distress, a potent inducer of oxidative stress and hsp70, can be partially ameliorated by feeding organic selenium. We attribute this observation to an enhanced GSH–GPX antioxidant system in organic selenium-fed chickens.     

Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion

Selenium is an essential dietary component for animals including humans, and there is increasing evidence for the efficacy of certain forms of selenium as cancer-chemopreventive compounds. In addition, selenium appears to have a protective effect at various stages of carcinogenesis including both the early and later stages of cancer progression. Mechanisms for selenium-anticancer action are not fully understood; however, several have been proposed: antioxidant protection, enhanced carcinogen detoxification, enhanced immune surveillance, modulation of cell proliferation (cell cycle and apoptosis), inhibition of tumor cell invasion and inhibition of angiogenesis. Research has shown that the effectiveness of selenium compounds as chemopreventive agents in vivo correlates with their abilities to affect the regulation of the cell cycle, to stimulate apoptosis and to inhibit tumor cell migration and invasion in vitro. This article reviews the status of knowledge concerning selenium metabolism and its anticancer effects with particular reference to the modulation of cell proliferation and the inhibition of tumor cell invasion.     

富硒益生菌的功效研究进展

硒是人体必需的微量元素,对人体健康有重要作用。益生菌能够将硒元素转化为有机硒,降低硒的毒性,同时硒又提高了益生菌的生物活性,富硒益生菌具备了硒和益生菌的双重功效。本文主要综述了近年来富硒益生菌的功效,如抗氧化、抑制有害菌、调节肠道菌群、抗癌等。     

Selenium,selenoproteins and cancer of the thyroid

Selenium is an essential mineral element with important biological functions for the whole body through incorporation into selenoproteins. This element is highly concentrated in the thyroid gland. Selenoproteins provide antioxidant protection for this tissue against the oxidative stress caused by free radicals and contribute, via iodothyronine deiodinases, to the metabolism of thyroid hormones. It is known that oxidative stress plays a major role in carcinogenesis and that in recent decades there has been an increase in the incidence of thyroid cancer. The anti-carcinogenic action of selenium, although not fully understood, is mainly attributable to selenoproteins antioxidant properties, and to the ability to modulate cell proliferation (cell cycle and apoptosis), energy metabolism, and cellular immune response, significantly altered during tumorigenesis. Researchers have suggested that different forms of selenium supplementation may be beneficial in the prevention and treatment of thyroid cancer; however, the studies have several methodological limitations. This review is a summary of the current knowledge on how selenium and selenoproteins related to thyroid cancer.     

Selenium as an adjuvant for modification of radiation response

Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.     

Selenium and sulfur in antioxidant protective systems: relationships with vitamin E and malaria.

The metabolic relationships among the antioxidant nutrients selenium, sulfur, and vitamin E are particularly close. Selenium and vitamin E have long been known to spare one another in certain nutritional diseases of animals, and selenium has been considered to have a key antioxidant defense function as a component of glutathione peroxidase. However, the antioxidant role of glutathione peroxidase has been questioned and new proteins containing selenium have been identified: phospholipid hydroperoxide glutathione peroxidase, selenoprotein P, and iodothyronine deiodinase. Glutathione peroxidase activity independent of selenium resides in the glutathione S-transferases. Glutathione participates in both enzymatic and nonenzymatic antioxidant defense systems. Some low-molecular weight selenium compounds (e.g., ebselen) exhibit glutathione peroxidase-like action. Certain low molecular weight thiols decompose peroxides nonenzymatically (e.g., the ovothiols). Murine malaria appears to be a useful experimental model for investigating interrelationships of selenium and vitamin E. Vitamin E deficiency protects against the parasite, especially when the mice are concurrently fed peroxidizable fat such as fish or linseed oils. Selenium deficiency, on the other hand, has little or no protective effect against the parasite. Any practical utility of pro-oxidant diets in combating human malaria remains to be determined.     

Selenium: potent stimulator of tyrosyl phosphorylation and activator of MAP kinase

Selenium, an essential biological trace element, is an integral component of several enzymes, and its use as a nutritional supplement has been popularized recently due to its potential role in low concentrations as an antioxidant and in higher concentrations as an anticancer agent. Selenium has also been reported to act as an insulin-mimetic agent with regard to normalization of blood glucose levels and regulation of some insulin-mediated metabolic processes. Little work, however, has been done concerning the pathway(s) by which this insulin-mimetic action occurs. In this study, we investigated the mechanism by which selenate exhibits insulin-mimetic properties in two different insulin responsive cell types, primary rat hepatocytes and 3T3 L1 adipocytes. We found that two proteins associated with the insulin signal cascade, the β-subunit of the insulin receptor and IRS-1, increased in tyrosyl phosphorylation in the presence of selenium. The third identified selenium activated signal protein, MAP kinase, has been implicated not only in the insulin signal transduction pathway but also in other growth factor-mediated responses. Using an in-gel activity assay for MAP kinase, we demonstrated that both the p42 and p44 MAP kinases are activated when either hepatocytes or adipocytes are incubated in the presence of selenate. In addition to the activation of these specific proteins, we found that selenium also eventually profoundly affected overall tyrosyl phosphorylation. Our results therefore show that selenium not only increased the phosphorylation of proteins identified in the insulin signal cascade but also affected the overall phosphorylation state of the cell.     

Absorption,distribution, metabolism and excretion (ADME) of oral selenium from organic and inorganic sources: A review

BackgroundSelenium is a trace element traditionally ingested either in its organic form via food or in its inorganic form through nutritional supplements, while selenium formulated as nanoparticles is a putative long-acting alternative. To understand the physiology and toxicology of the different selenium formulations, it is important to determine how their selenium content is absorbed, distributed, metabolised and excreted; therefore, we reviewed their biokinetics following oral exposure.MethodsWe retrieved and reviewed the literature on the absorption, distribution, metabolism, and excretion of oral exposure to different forms of selenium.ResultsSelenium in both the organic form (containing carbon to selenium chemical bonds) and the inorganic form is absorbed into the blood in humans. The mean normal blood level of many studies was 139 μg/L. There are indications that selenium from organic sources is more bioavailable than selenium from inorganic sources. Selenium is distributed throughout the body, including in breast milk. The elimination of selenium mainly involves the faecal and urinary pathways, whereas breath, saliva and hair are minor contributors. Urinary metabolites include trimethylselenium ions, selenosugars and Se-methylselenoneine.ConclusionSelenium is absorbed to a high extent, and selenium from organic sources is more bioavailable than from inorganic sources. Selenium, as expected as an essential trace element, is distributed throughout the body. Selenium is extensively metabolised, and various excretion metabolites have been identified in both urine and breath, while some selenium is also excreted via faeces.     

Selenium, a versatile trace element: current research implications

Selenium (Se), a trace element, has evolved from its toxic properties to an essential element. Se was known a potent antioxidant through glutathione peroxidase (selenium being part of this molecule). Later, many other selenium-binding proteins were discovered and their functions were tried to be known with unsuccessful results in many cases. Se is known to be involved in carcinogenesis, immune function, male reproduction, cardiovascular diseases etc. The specific mechanism of the involvement of the element is still not known. Recent research with application of modern research tools viz. bioinformatics, cDNA microarray and transgenesis have revealed the mechanism of selenium involvement in various processes. This review highlights mysterious and useful roles of selenium in biological processes.     

Interplay between Selenium Levels,Selenoprotein Expression,and Replicative Senescence in WI-38 Human Fibroblasts

Selenium is an essential trace element, which is incorporated as selenocysteine into at least 25 selenoproteins using a unique translational UGA-recoding mechanism. Selenoproteins are important enzymes involved in antioxidant defense, redox homeostasis, and redox signaling pathways. Selenium levels decline during aging, and its deficiency is associated with a marked increase in mortality for people over 60 years of age. Here, we investigate the relationship between selenium levels in the culture medium, selenoprotein expression, and replicative life span of human embryonic lung fibroblast WI-38 cells. Selenium levels regulate the entry into replicative senescence and modify the cellular markers characteristic for senescent cells. Whereas selenium supplementation extends the number of population doublings, its deficiency impairs the proliferative capacity of WI-38 cells. We observe that the expression of several selenoproteins involved in antioxidant defense is specifically affected in response to cellular senescence. Their expression is selectively controlled by the modulation of mRNA levels and translational recoding efficiencies. Our data provide novel mechanistic insights into how selenium impacts the replicative life span of mammalian cells by identifying several selenoproteins as new targets of senescence.     

Uptake, distribution, and speciation of selenoamino acids by human cancer cells: X-ray absorption and fluorescence methods

Selenium compounds exhibit chemopreventative properties at supranutritional doses, but the efficacy of selenium supplementation in cancer prevention is dependent on the chemical speciation of the selenium supplement and its metabolites. The uptake, speciation, and distribution of the common selenoamino acid supplements, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys), in A549 human lung cancer cells were investigated using X-ray absorption and fluorescence spectroscopies. X-ray absorption spectroscopy of bulk cell pellets treated with the selenoamino acids for 24 h showed that while selenium was found exclusively in carbon-bound forms in SeMet-treated cells, a diselenide component was identified in MeSeCys-treated cells in addition to the carbon-bound selenium species. X-ray fluorescence microscopy of single cells showed that selenium accumulated with sulfur in the perinuclear region of SeMet-treated cells after 24 h, but microprobe selenium X-ray absorption near-edge spectroscopy in this region indicated that selenium was carbon-bound rather than sulfur-bound. X-ray absorption and X-ray fluorescence studies both showed that the selenium content of MeSeCys-treated cells was much lower than that of SeMet-treated cells. Selenium was distributed homogeneously throughout the MeSeCys-treated cells.     

Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate

Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified.Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents.     

Increase in selenium requirements with physical activity loads in well-trained athletes is not linear

Selenium requirements in athletes are supposed to be increased with energy expenditure (EE) to preserve selenium status and an optimal antioxidant balance. The question of whether selenium intakes are related to EE and whether plasma selenium status induces up-regulation in erythrocyte endogenous antioxidant defense and decreases plasma oxidative damage markers in athletes was addressed. 118 well-trained athletes completed 7 d food and activities records in a cross-sectional study. Blood was sampled on day 8. Among the athletes, 23% of the males and 66% of the females had selenium intakes below two-third of the French RDA. Plasma selenium concentrations in most of less trained athletes were lower than the postulated concentration to be required to maximize erythrocyte GSH-Px activity. Athletes with the highest daily EE had the highest selenium intakes, percentage of vegetal protein intakes and plasma selenium concentrations. Only 2.6% of the athletes exhibited low plasma selenium concentrations (< 0.75 micromol/l). The relation between plasma selenium and EE was polynomial (r = 0.50; P < 0.005). Erythrocyte GSH-Px activity in athletes was not linked to selenium status. Selenium requirements are increased in athletes without being linearly related to EE.     

Selenium vitaminology: The connection between selenium,vitamin C,vitamin E,and ergothioneine

Selenium is connected to three small molecule antioxidant compounds, ascorbate, α-tocopherol, and ergothioneine. Ascorbate and α-tocopherol are true vitamins, while ergothioneine is a “vitamin-like” compound. Here we review how selenium is connected to all three. Selenium and vitamin E work together as a team to prevent lipid peroxidation. Vitamin E quenches lipid hydroperoxyl radicals and the resulting lipid hydroperoxide is then converted to the lipid alcohol by selenocysteine-containing glutathione peroxidase. Ascorbate reduces the resulting α-tocopheroxyl radical in this reaction back to α-tocopherol with concomitant production of the ascorbyl radical. The ascorbyl radical can be reduced back to ascorbate by selenocysteine-containing thioredoxin reductase. Ergothioneine and ascorbate are both water soluble, small molecule reductants that can reduce free radicals and redox-active metals. Thioredoxin reductase can reduce oxidized forms of ergothioneine. While the biological significance of this is not yet realized, this discovery underscores the centrality of selenium to all three antioxidants.     

Metabolic and functional defects in selenium deficiency

This paper is concerned with present-day knowledge of the biological role of selenium, of its interaction with other nutrients including trace elements, and with the importance of selenium in human nutrition and health. Selenium has been shown to be an integral part of glutathione peroxidase, which catalyses the reduction of a large range of lipid hydroperoxides and hydrogen peroxide. The interrelation between vitamin E, selenium and polyunsaturated fatty acids is complex. First, selenium in glutathione peroxidase may control intracellular levels of hydrogen peroxide, which affect the formation of active oxygen metabolites that may serve as initiators of lipid peroxidation; this role of selenium is closely related to that of superoxide dismutases, which control intracellular levels of the superoxide anion. Secondly, vitamin E may control the formation of lipid hydroperoxides through its antioxidant function, as well as possibly entering into a structural relation with membrane phospholipids. Thirdly, glutathione peroxidase may catalyse the reduction of lipid hydroperoxides, formed from membrane lipids, to hydroxyacids without detriment to the cellular economy. In the field of human nutrition, the lack of selenium has been shown to be the cause of a cardiomyopathy known as Keshan disease, occurring in the People's Republic of China. Blood selenium levels in patients from this area are compared with blood selenium levels in three other parts of the world and the conclusion is reached that the blood selenium level of populations in Keshan disease regions are exceptionally low and that Keshan disease is the first demonstration that selenium is an essential trace element for man.     

Involvement of selenoprotein P in protection of human astrocytes from oxidative damage

Selenoprotein P (SeP) is a highly glycosylated, selenium-rich plasma protein. Aside from its role as selenium carrier protein, an antioxidative function of SeP has been suggested. Astrocytes, which detoxify reactive oxygen species in the brain, were described as potential target cells of SeP. We investigated the expression of SeP in human astrocytes and its involvement in the protection of these cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage. We show that primary human astrocytes and the human astrocytoma cell line MOG-G-CCM express SeP as an unglycosylated protein, which is not secreted. SeP expression in astrocytes is constitutive. Preincubation of astrocytes with hepatocyte-derived SeP mimicks the protective effect of low-molecular-weight selenocompounds such as sodium selenite or selenomethionine against oxidative damage, shielding astrocytes from t-BHP-induced cytotoxicity. Selenium supplementation of astrocytes counteracts oxidative stress via an increase in expression and activity of the selenoenzyme cytosolic glutathione peroxidase (cGPx). Furthermore, specific downregulation of SeP expression by small interfering RNA decreases cell viability of human astrocytes and makes them more susceptible to t-BHP-induced cytotoxicity. Our results implicate an antioxidant activity of constitutively expressed SeP in selenium-deficient astrocytes, while during adequate selenium supply the enhanced protection against oxidative stress is exerted by cGPx.