硒化合物的制癌效能

硒是大多数动物和人的必需饮食营养物，以硒代半胱氨酸形式掺入12个以上的已知蛋白或酶。大多数但不是所有来自硒化合物的硒可有效地掺代半胱氨酸。硒的主要饮食形式是来自谷物和动物蛋白的L-硒代甲硫氨酸和来自动物蛋白的硒代半胱氨酸。水果和蔬菜通常含很低水平的硒。在经由补充达到超营养硒水平时，大多数但非所有硒化合物可减少动物和人自然发生的、病毒或化学诱导的癌瘤发生率。硒化学预防癌瘤的作用取决于饮食补充剂量和摄入硒的化学形式，在定量上，硒的饮食性化学预防作用在其满足硒酶和硒蛋白的必需作用的硒摄入量和可表达明显毒性的量之间展现。在体外和体内表达明显制癌效能的所有硒化合物的共同特征是它们与巯基的相互作用和产生自由基。     

微量元素硒与甲状腺

硒在甲状腺激素的合成、活化及代谢中发挥着重要作用。甲状腺在人体器官中含硒量最高。甲状腺特别是滤泡上皮细胞表达众多功能性含硒基半胱氨酸的酶，已确定的有：3类谷胱甘肽过氧化物酶、Ⅰ型5′-脱碘酶、硫氧还蛋白还原酶及硒蛋白P。因为甲状腺滤泡上皮细胞不断产生H2O2，故有效的抵御H2O2及活性氧中问产物的侵害对维护正常的甲状腺机能十分重要。动物实验表明即使给予充足的碘，如果有长期严重缺硒也将导致甲状腺坏死、纤维化。如见于扎伊尔中部的硒和碘都缺乏导致地方性克汀病、粘液性水肿。缺硒及血清硒水平低与甲状腺及其它器官肿瘤的发生密切相关。虽然硒摄入量影响含硒基半胱氨酸蛋白的表达及翻译，但硒的组织浓度与各种甲状腺硒蛋白之间尚无直接关系。提示在甲状腺囊肿、癌及自身免疫性疾病中，尚有其它因素参与调控硒蛋白表达的。     

脱碘酶基因多态性与疾病关系的研究进展

微量元素硒（Se）是一种人体必需的微量元素,在人体组织中主要是以硒半胱氨酸（Se-Cys）和硒蛋氨酸（Se—Met）的形式存在,构成了硒蛋白或含硒酶,是许多具有重要生物功能的硒酶的活性中心,与机体的免疫应答及抗氧化作用等生理功能密切相关。哺乳动物体内硒蛋白主要有谷胱甘肽过氧化物酶、脱碘酶家族（脱碘酶1、脱碘酶2和脱碘酶3）、SEPP、硒蛋白W、硒蛋白N和硫氧还蛋白等。脱碘酶是甲状腺激素代谢中最重要的转化酶,对维持机体甲状腺激素水平起着决定作用,很多的研究结果还表明,脱碘酶的基因多态性与许多疾病的发生有关,可能是相关疾病的易感基因。本文就脱碘酶基因多态性与疾病的关系研究做一综述,以期为相关疾病治疗与预防提供新的思路。     

患病婴幼儿童的硒含量

对５３９例患儿硒含量作了检测，结果表明９９％以上的患儿硒含量低于下限值。硒是人体重要含硒酶和硒蛋白的必需组分，具有重要的生物学作用，体内硒的缺乏导致免疫力低下，容易患病，必须注意小儿日常膳食中补硒。     

连续流动氢化物发生原子荧光光谱法测定保健品中的硒

硒是人体必需的微量元素之一 ,具有独特的生物活性。近些年来 ,研究发现硒是人体重要含硒酶与硒蛋白必需的组成部分 ,其在人体内约有 1/ 3参与谷胱甘肽酶的合成 ,催化还原谷胱甘肽还原人体内有害的过氧化物—具有抗氧化的特性 ,并且在人体肌肉细胞的生物氧化过程中发挥电子传递作用[1] ;同时在人的肌体内参与许多重要代谢过程。补充硒可抑制肿瘤和心血管疾病的发生 ,提高人体免疫能力 ,但人体摄入过量硒会引起中毒。因此 ,建立硒的快速、准确测定方法具有重要意义。目前测硒的分析方法有比色法[2 ] 、电化学方法[3 ] 、气相色谱法[4] 、中子…     

不同脑细胞系和脑区硒蛋白表达的生化分析

硒存在于各种具有重要生物学意义的硒蛋白中.硒优先掺入脑,提示它对脑的重要性,但到目前为止对脑的硒蛋白组学还知之甚少.因此,研究者利用75硒标记、凝胶电泳分离和放射自显影技术研究了不同脑区、不同亚细胞结构及几种脑细胞系中硒蛋白的表达.通过对硒缺乏大鼠标记硒蛋白的定量分析发现了硒的优先结合蛋白及其分布;共区分出21种硒蛋白,其中一种新的或修饰的15 kDa硒蛋白富含于小脑细胞胞质中.硒蛋白在不同脑区及同一脑区不同亚细胞结构中的表达是不同的.在某些细胞系中发现了一些细胞特异性硒蛋白.硒蛋白在单培养和共培养的内皮细胞与星形胶质细胞中分布模式有差别,这提示由其他细胞产生的中介分子可影响某一特定类型细胞中硒蛋白的表达.这种作用对硒在脑中的摄入和分布有重要意义,同时在其他组织硒代谢中也很重要.     

甲基硒半胱氨酸的生物利用率和毒性的研究

目的:以硒蛋氨酸为参照,研究甲基硒半胱氨酸的生物利用率和毒性。方法:通过硒积累、谷胱甘肽过氧化物酶和硫氧还蛋白还原酶活力比较生物利用率,通过急性毒性和短期硒耐受实验比较毒性。结果:两者对含硒酶的影响相同。硒蛋氨酸产生更高的硒积累,尤其是在高剂量硒水平。急性致死作用和短期硒耐受试验均显示硒蛋氨酸毒性低。结论:与硒蛋氨酸相比,甲基硒半胱氨酸有相等的含硒酶调节能力,特点是硒积累少,但具有较高的毒性。     

硒

<正>膳食硒摄入缺乏和过剩对人类健康影响一直是人们关注的焦点。国外对硒的认识源于动物硒中毒和缺乏。1973年发现硒是谷胱甘肽过氧化物酶(glutathione peroxidase,GPX)的必需组分,第一次揭示了硒具有生物活性。我国对硒的最初认识是上世纪六十年代湖北恩施地区的人体硒中毒。七十年代补硒有效控制克山病暴发流行使我们认识到硒对人体健康的重要性。这也为确认硒是人体必需微量元素奠定了基础。八十年代,硒在预防疾病和人体营养中作用的报告不断涌现。     

富硒灵芝的营养成分及其抗氧化能力研究

硒是人体谷胱甘肽过氧化物酶 (GSH- Px)的组成成分 ,是人体必需的微量元素 ,硒的抗氧化作用已有不少研究[1] 。人体的硒主要来源于食物 ,从营养学和生化代谢角度考虑 ,生物源有机硒以其吸收利用率高、毒副作用小等特点优越于无机硒。灵芝是药食两用菌 ,对增强机体体免疫力、抗癌、抗肿瘤方面研究也早有报导 [2 ] ,灵芝对某些微量元素特别是硒具有高度的富集作用 ,并把无机硒转化为有机硒 ,利于人体摄入。本实验采用的富硒灵芝是灵芝在加硒深层培养中 ,对无机硒进行生物转化而成为富含生物有机硒的灵芝 ,有机硒含量最高可达 60 0 0μg/g。…     

不同化学形式硒的毒性作用机制

硒是一种人体必需微量元素,但摄入过量可导致中毒,不同化学形式硒的毒性有差异,有关硒的毒性作用机制目前尚不清楚,其中最为流行的是活性氧自由基学说,另外,摄入过量的硒也可对机体的酶活性产生影响。     

Biomarkers of Selenium Status

The essential trace element, selenium (Se), has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites.     

Considerations on an Approach for Establishing a Framework for Bioactive Food Components

Bioactive food components have shown potential health benefits for more than a decade. Currently there are no recommended levels of intake [i.e., Dietary Reference Intakes (DRIs)] as there are for nutrients and fiber. DRIs for essential nutrients were based on requirements for each specific nutrient to maintain normal physiologic or biochemical function and to prevent signs of deficiency and adverse clinical effects. They were later expanded to include criteria for reducing the risk of chronic degenerative diseases for some nutrients. There are many challenges for establishing recommendations for intakes of nonessential food components. Although some nonessential food components have shown health benefits and are safe, validated biomarkers of disease risk reduction are lacking for many. Biomarkers of intake (exposure) are limited in number, especially because the bioactive compounds responsible for beneficial effects have not yet been identified or are unknown. Furthermore, given this lack of characterization of composition in a variety of foods, it is difficult to ascertain intakes of nonessential food components, especially with the use of food-frequency questionnaires designed for estimating intakes of nutrients. Various intermediary markers that may predict disease outcome have been used as functional criteria in the DRI process. However, few validated surrogate endpoints of chronic disease risk exist. Nonvalidated intermediary biomarkers of risk may possibly predict clinical outcomes, but more research is needed to confirm the associations between cause and effect. One criterion for establishing acceptable intermediary outcome indicators may be the maintenance of normal physiologic function throughout adulthood, which presumably would lead to reduced chronic disease risk. Multiple biomarkers of outcomes that demonstrate the same health benefit may also be helpful. It would be beneficial to continue to refine the process of setting DRIs by convening a workshop on establishing a framework for nonessential food components that would take into consideration intermediary biomarkers indicative of optimal health.     

The argument for increasing selenium intake

The essential trace mineral, Se, is of fundamental importance to human health. As a constituent of selenoproteins it plays both structural and enzymic roles, in the latter context being best known as an antioxidant and catalyst for the production of active thyroid hormone. While Se-deficiency diseases have been recognised for some time, evidence is mounting that less-overt deficiency can also cause adverse health effects and furthermore, that supra-nutritional levels of Se may give additional protection from disease. In the context of these effects, low or diminishing Se status in some parts of the world, notably in some European countries such as the UK, is giving cause for concern. While deficiency has an adverse effect on immunocompetence, Se supplementation appears to enhance the immune response. Se appears to be a key nutrient in counteracting certain viral infections; thus, in a Se-deficient host the benign coxsackie virus becomes virulent, causing heart damage, the influenza virus causes more serious lung pathology and HIV infection progresses more rapidly to AIDS. Long recognised as essential for successful animal reproduction, Se is required for human sperm maturation and sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking Se to cardiovascular disease risk, although other conditions involving oxidative stress and inflammation have shown some association with Se status. There is growing evidence that higher Se intakes are associated with reduced cancer risk. While persuasive evidence already exists to suggest that additional Se would be beneficial in some health conditions, results from intervention trials underway or planned have the potential to reinforce or refute the argument for increasing Se intake.     

Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research

In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available.     

Selenium: its role as antioxidant in human health

Selenium (Se) is an essential trace element, and its low status in humans has been linked to increased risk of various diseases, such as cancer and heart disease. In recent years, Se research has attracted tremendous interest because of its important role in antioxidant selenoproteins for protection against oxidative stress initiated by excess reactive oxygen species (ROS) and reactive nitrogen species (NOS). The synthesis of selenoproteins requires a unique incorporation of amino acid selenocysteine (Sec) into proteins directed by the UGA codon, which is also a termination codon. Interest in Se research has led to the discovery of at least 30 selenoproteins; however, the biochemical functional roles of some of these selenoproteins are still unknown. Besides in the form of selenoproteins, Se can exist in many different chemical forms in biological materials either as organic Se compounds, such as selenomethionine and dimethylselenide, and inorganic selenites and selenates. In foods, Se is predominantly present as selenomethionine, which is an important source of dietary Se in humans, and also as a chemical form that is commonly used for Se supplements in clinical trials. Concern for potential deficiency diseases associated with low Se status has led to the establishment of the recommended daily requirements for Se in many countries. However, excess Se intakes through supplementation and its potential misuse as health therapy could also pose a risk of adverse health effects if its use is not properly regulated.     

Selenium in global food systems

Food systems need to produce enough of the essential trace element Se to provide regular adult intakes of at least 40 microg/d to support the maximal expression of the Se enzymes, and perhaps as much as 300 microg/d to reduce risks of cancer. Deprivation of Se is associated with impairments in antioxidant protection, redox regulation and energy production as consequences of suboptimal expression of one or more of the Se-containing enzymes. These impairments may not cause deficiency signs in the classical sense, but instead contribute to health problems caused by physiological and environmental oxidative stresses and infections. At the same time, supranutritional intakes of Se, i.e. intakes greater than those required for selenocysteine enzyme expression, appear to reduce cancer risk. The lower, nutritional, level is greater than the typical intakes of many people in several parts of the world, and few populations have intakes approaching the latter, supranutritional, level. Accordingly, low Se status is likely to contribute to morbidity and mortality due to infectious as well as chronic diseases, and increasing Se intakes in all parts of the world can be expected to reduce cancer rates.     

Analyzed dietary intakes,plasma concentrations of zinc,copper, and selenium,and related antioxidant enzyme activities in hospitalized elderly women.

The purpose of the study was to assess the actual dietary intakes of zinc (Zn), copper (Cu) and selenium (Se) intakes in relation with some indicators of trace element status in a selected group of hospitalized elderly patients.

24 elderly women aged 76-99 years were recruited in the Geriatric Department of the Grenoble University Hospital.

Zn, Cu, and Se dietary intakes were estimated by duplicate portion analysis. Plasma trace element concentrations, Cu-Zn superoxide dismutase (Cu-Zn SOD) and Se glutathione peroxidase (Se GSH-Px) activities were determined in parallel.

Mean daily intakes of Zn (5.6 mg), Cu (0.67 mg), and Se (23 micrograms) were low, in relation with poor energy intake and nutrient densities. Zn and Se levels in plasma were lower and plasma Cu increased compared to reference values obtained from healthy younger subjects. Thirty-eight percent of the elderly patients had plasma Zn concentrations < 10.7 mumol/l, but Cu status appeared adequate as suggested by the lack of decline in Cu-Zn SOD activity. A high proportion of plasma Se concentrations < 0.76 mumol/l and the parallel decrease in erythrocyte and plasma GSH-Px activities suggest a Se deficiency in this population.

Our findings indicate that French hospitalized elderly patients may be at risk of Zn and Se marginal status and present altered antioxidant defenses in relation with low dietary intakes. It underlines the interest of supplementation studies in this population.     

Functional indicators of iodine and selenium status.

The micronutrient I, which has only one known biological function as a component of thyroid hormones, contrasts with Se, which is essential for many biochemical pathways through a range of Se-containing proteins. Thus, for I it is less complicated to propose and validate biochemical or functional markers which represent the adequacy or otherwise of dietary intake than it is to perform the same task for Se. Plasma thyroid-stimulating hormone provides a good indicator of functional I status, since levels of the hormone increase to compensate for any inadequacy in available dietary I. This increase occurs even when problems are caused by goitrogens restricting utilization of dietary I that otherwise would be adequate. In contrast, there are many potential indicators of Se status, especially since the many Se-containing proteins relate to different biochemical functions in the body. However, determination of the different GSH peroxidase (EC 1.11.1.9) activities in blood or tissue may give a useful indication of 'functional Se status', since these selenoproteins are often the most sensitive indicators of dietary Se intake. This approach has been successful in many experiments where animals of a similar genetic background have consumed diets which differ only in their Se content. Unfortunately, use of indicators of Se status in human populations may be complicated by differences (possibly genetic) between individuals that increase variability of selenoenzyme activities. The most appropriate indicator of functional Se status may also vary with other dietary conditions such as vitamin E or I deficiencies which may interact with Se deficiency. However, taking particular circumstances into account, determination of blood or tissue selenoprotein activity can provide a useful marker of adequacy of dietary Se supply for maintaining optimal health.     

Biomarkers of intermediate endpoints in environmental and occupational health

The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal aberrations (CA), sister chromatid exchanges and micronuclei (MN). The validation of biomarkers includes measurements of sensitivity and specificity of biomarkers and round robin tests to ensure reproducible protocols within different laboratories. The predictive value of biomarkers with respect to adverse health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained cytogeneticists. Less time consuming, but robust biomarkers, sensitive to environmental exposures are suggested. From the selection of developed biomarkers, the comet assay is highly sensitive to lifestyle exposures, often confounding the output, while MN in lymphocytes seem promising with respect to laboratory and health effect (cancer) validity. Also, new biomarkers exploiting the new 'omics' technologies are being developed. A number of ethical issues arise from the use of biomarkers with a predictive value aiming at respecting the autonomy of the study person in participation (only upon written informed consent and with obligations of withdrawal at any time), access to personal information (right to know and right not to know the study result) and securing proper data management (data protection to avoid misuse in employment, insurance, loaning and learning opportunities).     

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development

The proposed National Children's Study has helped raise awareness of the issues related to children's health and the importance of monitoring the growth and development of children from preconception through adulthood. Many genetic predispositions can adversely impact the normal development process, and various environmental exposures have been linked to adverse reproductive health in rodent models and a small number of accidental human exposures. To monitor reproductive health and identify adverse effects at the earliest possible juncture, investigators must develop a network of biomarkers covering all stages and aspects of reproductive development and function. Biomarkers are biological indicators that can be measured repeatedly and are informative on one or more aspects of biological development or function. They can range from the anatomical level down to the molecular level and may provide information on the nature of an exposure, the effect of an exposure, or the susceptibility of individuals or populations to the toxic effects of an exposure. In theory, biomarkers can be used to monitor a wide variety of conditions and responses ranging from abnormal development to early indicators of late-onset disease. The main stumbling block with this theory has been finding appropriate biomarkers for particular conditions and exposures. Such biomarkers must be easily accessible, robust, and sensitive. Ideally, they will be expressed across a large section of the population, and can be monitored quickly, easily, conveniently, and with minimal cost. In this review, we discuss some of the current and emerging biomarkers of human pubertal development.