硒缺乏与阿尔茨海默症

微量元素硒对维持中枢神经系统的生物功能具有重要作用。生物摄入硒后优先供给脑部。长期缺硒会引起包括阿尔茨海默症（AD）在内的脑疾病。AD的病理特征为β-．淀粉样肽聚集形成老年斑和tau蛋白过度磷酸化造成神经纤维缠结。氧化应激和信号转导紊乱在AD形成过程中具有重要作用。硒缺乏会影响AD发生发展的各个环节,与认知功能降低和AD形成密切相关。对近年有关硒与AD关系的研究进展进行综述,着重总结了硒缺乏对氧化应激、信号转导以及AD病理特征形成的作用和机制,探讨补硒延缓AD形成的可能性。     

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。     

Selenium and thyroid function in infants, children and adolescents

Selenium is an integral component of the enzymes glutathione peroxidase (GPx) and iodothyronine deiodinases. Although selenium nutrition could conceivably affect thyroid function in infants, children and adolescents, available data suggest that the effect of selenium deficiency on thyroid function is relatively modest. In patients with isolated selenium deficiency (such as patients with phenylketonuria receiving a low-protein diet), peripheral thyroid hormone metabolism is impaired but there are no changes in thyrotropin (TSH) or clinical signs of hypothyroidism, suggesting that these patients are euthyroid. Selenium supplementation may be advisable to optimize tissue GPx activity and prevent potential oxidative stress damage. In areas where combined selenium and iodine deficiencies are present (such as endemic goiter areas in Central Africa), selenium deficiency may be responsible for the destruction of the thyroid gland in myxoedematous cretins but may also play a protective role by mitigating fetal hypothyroidism. In these areas, selenium supplementation should only be advocated at the same time or after iodine supplementation. In patients with absent or decreased production of thyroid hormones and who rely solely on deiodination of exogenous L-thyroxine for generation of the active triiodothyronine (such as patients with congenital hypothyroidism), selenium supplementation may optimize thyroid hormone feedback at the pituitary level and decrease stimulation of the residual thyroid tissue.     

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.     

Selenoprotein gene expression during selenium-repletion of selenium-deficient rats

Selenium repletion of selenium-deficient rats with 20 μg selenium/kg body weight as Na₂SeO₃ was used as a model to investigate the mechanisms that control the distribution of the trace element to specific selenoproteins in liver and thyroid. Cytosolic glutathione peroxidase (cGSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGSHPx), and iodothyronine 5′-deiodinase (IDI) activities were all transiently increased in liver 16 to 32 h after ip injection with selenium. However, only cGSHPx and PHGSHPx activities increased in the thyroid where IDI activity was already increased by selenium deficiency. These responses were owing to synthesis of the seleoproteins on newly synthesised and/or existing mRNAs. The selenoprotein mRNAs in the thyroid gland were increased two- and threefold after the transitory increases in selenoprotein activity. In contrast, there were parallel changes in selenoprotein mRNAs and enzyme activities in the liver, with no prolonged rises in mRNA levels. The organ differences suggest that increased thryotrophin (TSH) concentrations, which are known to induce thyrodial IDI and mRNA, may control the mRNAs for all the thyroidal selenoproteins investigated and be a major mechanism for the preservation of thyroidal selenoproteins when selenium supplies are limited.     

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.     

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.     

Selenium deficiency inhibits prostacyclin release and enhances production of platelet activating factor by human endothelial cells

Selenium is an essential component of glutathione peroxidase, an enzyme which protects cells against peroxidation and controls concentrations of intracellular peroxides. Since selenium deficiency is clinically associated with an increased degree of atherosclerosis, the effects of selenium deficiency on prostacyclin (PGI2) and platelet activating factor (PAF) production by cultured human umbilical vein endothelial cells (HUVEC) were investigated. In selenium-deficient HUVEC, histamine-induced PGI2 synthesis was significantly decreased when compared to selenium-supplemented HUVEC; in contrast, histamine-induced PAF production was increased by selenium deficiency. Histamine-induced inositol trisphosphate and [Ca2+]i responses and the conversion of PGG2 and PGH2 to PGI2 were not altered by selenium deficiency. However, selenium deficiency decreased the conversion of exogenous arachidonate to PGI2 and markedly suppressed glutathione peroxidase activity. These results suggest that selenium deficiency, by decreasing glutathione peroxidase activity, makes HUVEC susceptible to peroxide-induced inhibition of the cyclooxygenase activity of PGH2 synthase, resulting in decreased PGI2 production. These changes may alter platelet function in vivo and thus play a role in the increased incidence of atherosclerosis reported in selenium-deficient individuals.     

Selenium status in an iodine deficient population of the West Ivory Coast

Selenium is an essential trace element which is part of the active site of seleno-dependent glutathione peroxidase and type 1 deiodinase. Therefore, it plays a key role in thyroid hormone metabolism. The present work was undertaken in order to evaluate selenium status in two Ivory Coast populations: the first with high (Glanlé) and the second with low (Abidjan) prevalence of iodine deficiency. Selenium, glutathione peroxidase, glutathione reductase, glutathione and diglutathione were determined in blood and/or urine. In plasma and erythrocytes, selenium and glutathione peroxidase were dramatically low in Glanlé. Compared to Abidjan, selenium, glutathione peroxidase, vitamin E and riboflavin status were decreased whereas diglutathione was increased in Glanlé. The results clearly demonstrate a selenium deficiency and suggest an oxidant stress in Glanlé. Causes and consequences of this selenium deficiency and oxidant stress remain to be determined.     

Accumulation and metabolism of selenium by yeast cells

This paper examines the process of selenium bioaccumulation and selenium metabolism in yeast cells. Yeast cells can bind elements in ionic from the environment and permanently integrate them into their cellular structure. Up to now, Saccharomyces cerevisiae, Candida utilis, and Yarrowia lipolytica yeasts have been used primarily in biotechnological studies to evaluate binding of minerals. Yeast cells are able to bind selenium in the form of both organic and inorganic compounds. The process of bioaccumulation of selenium by microorganisms occurs through two mechanisms: extracellular binding by ligands of membrane assembly and intracellular accumulation associated with the transport of ions across the cytoplasmic membrane into the cell interior. During intracellular metabolism of selenium, oxidation, reduction, methylation, and selenoprotein synthesis processes are involved, as exemplified by detoxification processes that allow yeasts to survive under culture conditions involving the elevated selenium concentrations which were observed. Selenium yeasts represent probably the best absorbed form of this element. In turn, in terms of wide application, the inclusion of yeast with accumulated selenium may aid in lessening selenium deficiency in a diet.     

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.     

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.     

Assessing the dispersive and electrostatic components of the selenium–aromatic interaction energy by DFT

Selenium has been increasingly recognized as an important element in biological systems, which participates in numerous biochemical processes in organisms, notably in enzyme reactions. Selenium can substitute sulfur of cysteine and methionine to form their selenium analogues, selenocysteine (Sec) and selenomethionine (SeM). The nature of amino acid pockets in proteins is dependent on their composition and thus different non-covalent forces determine the interactions between selenium of Sec or SeM and other functional groups, resulting in specific biophysical behavior. The discrimination of selenium toward sulfur has been reported. In order to elucidate the difference between the nature of S-π and Se-π interactions, we performed extensive DFT calculations of dispersive and electrostatic contributions of Se-π interactions in substituted benzenes/hydrogen selenide (H₂Se) complexes. The results are compared with our earlier reported S-π calculations, as well as with available experimental data. Our results show a larger contribution of dispersive interactions in Se-π systems than in S-π ones, which mainly originate from the attraction between Se and substituent groups. We found that selenium exhibits a strong interaction with aromatic systems and may thus play a significant role in stabilizing protein folds and protein–inhibitor complexes. Our findings can also provide molecular insights for understanding enzymatic specificity discrimination between single selenium versus a sulfur atom, notwithstanding their very similar chemical properties.     

Inhibition of type I and type II iodothyronine deiodinase activity in rat liver, kidney and brain produced by selenium deficiency.

Selenium deficiency for periods of 5 or 6 weeks in rats produced an inhibition of tri-iodothyronine (T3) production from added thyroxine (T4) in brain, liver and kidney homogenate. This inhibition was reflected in plasma T4 and T3 concentrations, which were respectively increased and decreased in selenium-deficient animals. Although plasma T4 levels increased in selenium-deficient animals, this did not produce the normal feedback inhibition on thyrotropin release from the pituitary. Selenium deficiency was confirmed in the animals by decreased selenium-dependent glutathione peroxidase (Se-GSH-Px) activity in all of these tissues. Administration of selenium, as a single intraperitoneal injection of 200 micrograms of selenium (as Na2SeO3)/kg body weight completely reversed the effects of selenium deficiency on thyroid-hormone metabolism and partly restored the activity of Se-GSH-Px. Selenium administration at 10 micrograms/kg body weight had no significant effect on thyroid-hormone metabolism or on Se-GSH-Px activity in any of the tissues studied. The characteristic changes in plasma thyroid-hormone levels that occurred in selenium deficiency appeared not to be due to non-specific stress factors, since food restriction to 75% of normal intake or vitamin E deficiency produced no significant changes in plasma T4 or T3 concentration. These data are consistent with the view that the Type I and Type II iodothyronine deiodinase enzymes are seleno-enzymes or require selenium-containing cofactors for activity.     

Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and zebrafish embryos against ethanol induced oxidative stress

Alcoholic cardiomyopathy is the damage caused to the heart muscles due to high level of alcohol consumption resulting in enlargement and inflammation of the heart. Selenium is an important trace element that is beneficial to human health. Selenium protects the cells by preventing the formation of free radicals in the body. In the present study, protein mediated synthesis of SeNPs was investigated. Two different sizes of SeNPs were synthesized using BSA and keratin. The synthesized SeNPs were characterized by scanning electron microscopy (SEM) with elemental composition analysis Energy Dispersive X-ray spectroscopy(EDX) and X-ray diffraction (XRD). This study demonstrates the in vitro and in vivo antioxidative effects of sodium selenite and SeNPs. Further selenium and SeNPs were evaluated for their ability to protect against 1% ethanol induced oxidative stress in H9C2 cell line. The selenium and SeNPs were found to reduce the 1% ethanol-induced oxidative damage through scavenging intracellular reactive oxygen species. The selenium and SeNPs could also prevent pericardial edema induced ethanol treatment and reduced apoptosis and cell death in zebrafish embryos. The results indicate that selenium and SeNPs could potentially be used as an additive in alcoholic beverage industry to control the cardiomyopathy.     

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.     

Serum Total Selenium Status in Greek Adults and Its Relation to Age. The ATTICA Study Cohort

The trace element selenium is an essential micronutrient for human health and its low levels in serum are implicated in the pathogenesis of several chronic diseases. Therefore, the determination of total selenium in serum may contribute to the assessment of the health and nutritional status of certain populations. The objective of the present work was to determine total selenium in the serum of 506 healthy volunteers that participated in the ATTICA study. Selenium was determined in serum by using the technique of inductively coupled plasma mass spectrometry. The mean serum selenium concentration was determined to be 91.8 ± 33.7 μg/L (N = 506); 87.6% of women and 88.5% of men had serum selenium concentration below 125 μg/L, the cutoff considered to be required for optimal glutathione peroxidase activity. No association was found between serum selenium levels and the gender of the participants while a significant decline of selenium with age (p < 0.0001) was observed. According to our results, no anthropometric, lifestyle, nutritional, or biochemical indices were able to affect the association between serum selenium and age. This result may indicate that other factors such as selenium distribution as well as retention may be affecting the relationship between serum selenium and age.     

Selenium and cardiovascular disease.

For humans, ecological and epidemiological results are reported that show a relationship between the serum selenium concentration and cardiovascular disease in populations where low serum selenium concentrations are found, e.g., in Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland, and Sweden, subnormal serum selenium and partially whole blood selenium concentrations are reported in patients with acute myocardial infarction. For patients with coronary arteriosclerosis, subnormal serum selenium concentrations are reported from the USA and Germany and subnormal whole blood selenium concentrations from Germany. Subnormal serum and subnormal whole blood selenium concentrations of patients with cardiomyopathy are reported from non Keshan disease affected areas in Germany, France, and China. In selenium deficiency, an accumulation of lipid peroxides in the heart may occur, especially under ischemic conditions and if ischemic tissue is reperfused. Lipid peroxides in the heart may damage the cell membrane and may lead to an impaired calcium transport with an uncontrolled calcium accumulation in the cell. This may result in an activation of phospholipids, and, in consequence, to an enhanced formation of arachidonic acid. An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxane, causing enhanced blood pressure and platelet aggregability. From animal experiments, it is known that selenium protects against cardiotoxic elements, cardiotoxic xenobiotics, and viral infections that affect the heart. Selenium deficiency may also be a secondary factor in the causation of hypertension and myocardial ischemia.