The role of selenium content of wheat in the human nutrition: A literature review

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Selenomethionine: A Pink Trojan Redox Horse with Implications in Aging and Various Age-Related Diseases

Selenium is an essential trace element. Although this chalcogen forms a wide variety of compounds, there are surprisingly few small-molecule organic selenium compounds (OSeCs) in biology. Besides its more prominent relative selenocysteine (SeCys), the amino acid selenomethionine (SeMet) is one example. SeMet is synthesized in plants and some fungi and, via nutrition, finds its way into mammalian cells. In contrast to its sulfur analog methionine (Met), SeMet is extraordinarily redox active under physiological conditions and via its catalytic selenide (RSeR’)/selenoxide (RSe(O)R’) couple provides protection against reactive oxygen species (ROS) and other possibly harmful oxidants. In contrast to SeCys, which is incorporated via an eloquent ribosomal mechanism, SeMet can enter such biomolecules by simply replacing proteinogenic Met. Interestingly, eukaryotes, such as yeast and mammals, also metabolize SeMet to a small family of reactive selenium species (RSeS). Together, SeMet, proteins containing SeMet and metabolites of SeMet form a powerful triad of redox-active metabolites with a plethora of biological implications. In any case, SeMet and its family of natural RSeS provide plenty of opportunities for studies in the fields of nutrition, aging, health and redox biology

Selenium

prepared by Syracuse Research Corporation under contract no. 205-1999-00024 ; prepared for U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry."September 2003."Chemical manager(s)/author(s): John Risher ... [et al.]--P. ix."A Toxicological Profile for selenium, Draft for Public Comment was released in September, 2001. This edition supersedes any previously released draft or final profile"--P. iii."This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987"--P. v.Also available via the World Wide Web.Includes bibliographical references (p. 315-411)

The Use of Dietary Additives in Fish Stress Mitigation: Comparative Endocrine and Physiological Responses

In the last years, studies on stress attenuation in fish have progressively grown. This is mainly due to the interest of institutions, producers, aquarists and consumers in improving the welfare of farmed fish. In addition to the development of new technologies to improve environmental conditions of cultured fish, the inclusion of beneficial additives in the daily meal in order to mitigate the stress response to typical stressors (netting, overcrowding, handling, etc.) has been an important research topic. Fish are a highly diverse paraphyletic group (over 27,000 species) though teleost infraclass include around 96% of fish species. Since those species are distributed world-wide, a high number of different habitats and vital requirements exist, including a wide range of environmental conditions determining specifically the stress response. Although the generalized endocrine response to stress (based on the release of catecholamines and corticosteroids) is detectable and therefore provides essential information, a high diversity of physiological effects have been described depending on species. Moreover, recent omics techniques have provided a powerful tool for detecting specific differences regarding the stress response. For instance, for transcriptomic approaches, the gene expression of neuropeptides and other proteins acting as hormonal precursors during stress has been assessed in some fish species. The use of different additives in fish diets to mitigate stress responses has been deeply studied. Besides the species factor, the additive type also plays a pivotal role in the differentiation of the stress response. In the literature, several types of feed supplements in different species have been assayed, deriving in a series of physiological responses which have not focused exclusively on the stress system. Immunological, nutritional and metabolic changes have been reported in these experiments, always associated to endocrine processes. The biochemical nature and physiological functionality of those feed additives strongly affect the stress response and, in fact, these can act as neurotransmitters or hormone precursors, energy substrates, cofactors and other essential elements, implyingmulti-systematic and multi-organic responses. In this review, the different physiological responses among fish species fed stress-attenuating diets based on biomolecules and minerals have been assessed, focusing on the endocrine regulation and its physiological effects

Evaluation of the maximum limits for selenium in Atlantic salmon feeds

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Doctor of Philosophy

dissertationLung cancer is the most fatal and second most prevalent type of cancer in the United States with a current five-year survival rate of only 16%. Thus, novel therapeutic agents to both prevent and treat lung cancer are necessary. One such agent is selenium, a micronutrient present in the diet. Epidemiological studies and supplementation trials with selenium have shown it to decrease lung cancer incidence and mortality. Selenium has also been shown to decrease lung tumor burden in animal studies, with the benefit being compound dependent. The mechanisms of action of selenium in cancer remain under investigation, but may relate to cellular redox status regulation. The hypothesis of this work is that distinct selenocompounds alter the cellular redox state of human lung cells through the Nrf2/antioxidant response element (ARE) pathway and the antioxidant selenoprotein thioredoxin reductase 1 (TR1). This hypothesis was tested using three specific aims: 1. Determine the redox effects of selenocompounds in A549 adenocarcinoma cells and BEAS-2B nonmalignant bronchial epithelial cells. 2. Investigate the ability of selenocompounds to activate the Nrf2/ARE pathway in nonmalignant BEAS-2B cells. 3. Determine if TR1 modulates the cytotoxcity of selenocompounds in malignant A549 cells. iv Several selenocompounds were investigated, including the selenoamino acids selenomethionine and selenocystine, the selenocysteine prodrugs 2-butyl selenazolidine- 4(R)-carboxylic acid (BSCA) and 2-cyclohexylselenazolidine-4(R)-carboxylic acid (ChSCA), and methylseleninic acid (MSA). This work indicates that selenium can modulate cellular redox status, but the effects are compound and cell-line specific. Selenocystine and ChSCA induced oxidative stress in A549 cells and activated the Nrf2 pathway in BEAS-2B cells. Selenocystine, ChSCA and BSCA also demonstrated enhanced cytotoxicity in A549 cells with TR1 knockdown, which was related to their ability to deplete intracellular glutathione. MSA produced a reductive stress in A549 cells and activated the Nrf2 pathway in BEAS-2B cells, but its cytotoxicity was not altered by TR1 status. Selenomethionine failed to modulate cellular redox status, activate the Nrf2 pathway, or demonstrate enhanced cytotoxicity with TR1 knockdown. These findings further demonstrate that selenium has compound-dependent redox effects and certain compounds, namely selenocystine and ChSCA, may have actions as both cancer preventive and anti-tumor agents in the lung

The Effect of Vitamin E, Selenomethionine and Sodium Selenite Supplementation in Laying Hens

In trial 1, 3 levels of dl-α-tocopheryl acetate (0, 50, 100 IU/kg), and 3 levels of supplemental sodium selenite (SS) (0, 0.25, 0.50 ppm), were added to a corn-soybean meal basal diet to evaluate their effects on egg quality variables, and deposition in egg yolk. Adding 50 IU/kg dl- α-tocopheryl acetate in the diet lowered aged yolk pH. Alpha-tocopherol in yolks increased with increasing vitamin E. As Se level increased in the diet, yolk Se content increased. There was a vitamin E by Se interaction affecting yolk Se content, but the highest level of Se in the yolk achieved when using 0.5 ppm Se from either source with no vitamin E. Trial 2 was conducted to investigate the effects of using organic vs. inorganic Se on egg quality, egg yolk vitelline membrane strength, and glutathione peroxidase activity in the liver and shell gland of hens. Hens were fed a corn-soybean meal basal diet supplemented with 0, 0.2 ppm selenomethionine (SM), 0.2 ppm SS, 0.4 SM, or 0.4 ppm SS. Supplementing SS at 0.2 ppm or SM at 0.4 ppm had the same effect to improve the VMS. In trial 3, hens were fed the same dietary treatments as in the second trial and added to a semi-purified corn starch-soybean meal basal diet. Yolk Se content was higher in all treatments supplemented with Se from either source than the control diet. There was an interaction effect of Se source and level on albumen Se content; albumen Se content increased when SM levels in the diet increased, whereas when SS levels increased in the diet, there was no increase in egg albumen Se content. In summary, our results indicate that vitamin E and Se supplementation from the organic and inorganic sources can be a good practice to increase some of the egg quality parameters, but more research need to be conducted when the basal levels of Se are low. Advisor: Sheila E. Scheidele

Cellular transport, metabolism and toxicity of selenium in rainbow trout (Oncorhynchus mykiss)

The present research was designed to investigate the mechanisms of cellular transport, metabolism and toxicity of selenium [inorganic (selenite) and organic (selenomethionine)] in a model teleost, rainbow trout (Oncorhynchus mykiss), using both in vitro and in vivo experimental approaches. The transport properties of selenite and its thiol (glutathione and cysteine) reduced forms were examined in isolated enterocytes and hepatocytes. The kinetics of selenite uptake revealed a linear profile in both cell types, suggesting a low affinity transport process. However, the uptake kinetics was different between the two cell types in the presence of extracellular glutathione, since a concentration-dependent Hill uptake kinetics was recorded in enterocytes, while a linear kinetics persisted in hepatocytes. Both cysteine and glutathione augmented cellular selenium accumulation in these cells. The selenium transport was found to be energy independent, but sensitive to the extracellular pH and inorganic mercury. The pharmacological examination suggested that the cellular transport of selenite is primarily mediated by anion transport systems (e.g., sulphite transporters and/or bicarbonate transporters), although cell-specific differences in transport efficiency was apparent. The metabolism of selenite, selenate and selenomethionine in hepatocytes was examined using X-ray absorption near edge structure spectroscopy (XANES). Inorganic and organic forms of selenium appeared to be metabolized via different cellular pathways, as both selenite and selenate were found to be metabolized into elemental selenium, whereas selenocystine constituted the primary metabolite of selenomethionine. My findings also suggested direct enzymatic transformation of selenomethionine into methylselenol at high exposure level, a process that leads to enhanced intracellular reactive oxygen species generation because of the redox-reactive properties of methylselenol. To validate the metabolite profile of selenium observed in in vitro studies, the tissue-specific differences in selenium metabolism in vivo was analyzed in fish exposed to elevated dietary selenomethionine for two weeks. Similar to the observation in hepatocytes, selenocystine and selenomethionine were found to be the major selenium species across tissues, although there were differences in their relative proportion in different tissues. In addition, a good correlation between the total selenium burden and selenocystine fraction was recorded among all the major tissues except gonads. To understand the role of oxidative stress in cellular toxicity of selenium, isolated trout hepatocytes were exposed to increasing dosage of selenite and selenomethionine over a period of 24h. Selenite was found to be 10 times more toxic than selenomethionine to the hepatocytes. Both selenite and selenomethionine induced rapid generation of reactive oxygen species, which subsequently triggered an upregulation of enzymatic antioxidants. Interestingly, a sharp dose-dependent decrease in intracellular thiol redox (reduced to oxidized glutathione ratio) was recorded with exposure to both selenite and selenomethionine, indicating that glutathione plays an important role in mediating selenium toxicity. At the high exposure dosage, both selenium compounds compromised membrane and DNA integrity, disrupted intracellular calcium homeostasis, and induced enzymatic apoptosis pathway, ultimately leading to cell death via aponecrosis. These findings suggested that high selenium exposure causes cellular toxicity by inducing a rapid loss of the intracellular reducing milieu. Overall, the findings from the present study provided novel information on the transport, metabolism and toxicity of selenium in fish. This fundamental information will be useful in understanding the chemical species-specific toxicity of selenium in fish, and may help in identifying cellular biomarkers for assessing the health of selenium-impacted natural fish populations