Selenium (Se) is an important micronutrient and essential trace element for both humans and animals, which exist in the environment ubiquitously. Selenium deficiency is an important issue worldwide, ...with various reported cases of its deficiency. Low selenium contents in some specific terrestrial environments have resulted in its deficiency in humans. However, high levels of selenium in the geochemical environment may have harmful influences and can cause a severe toxicity to living things. Due to its extremely narrow deficiency and toxicity limits, selenium is becoming a serious matter of discussion for the scientists who deals with selenium-related environmental and health issues. Based on available relevant literature, this review provides a comprehensive data about Se sources, levels, production and factors affecting selenium bioavailability/speciation in soil, characteristics of Se, biogeochemical cycling, deficiency and toxicity, and its environmental transformation to know the Se distribution in the environment. Further research should focus on thoroughly understanding the concentration, speciation, Se cycling in the environment and food chain to effectively utilize Se resources, remediate Se deficiency/toxicity, and evaluate the Se states and eco-effects on human health.
Sepp1 is a widely expressed extracellular protein that in humans and mice contains 10 selenocysteine residues in its primary structure. Extra-hepatic tissues take up plasma Sepp1 for its selenium via ...apolipoprotein E receptor-2 (apoER2)-mediated endocytosis. The role of Sepp1 in the transport of selenium from liver, a rich source of the element, to peripheral tissues was studied using mice with selective deletion of Sepp1 in hepatocytes (Sepp1c/c/alb-cre+/− mice). Deletion of Sepp1 in hepatocytes lowered plasma Sepp1 concentration to 10% of that in Sepp1c/c mice (controls) and increased urinary selenium excretion, decreasing whole-body and tissue selenium concentrations. Under selenium-deficient conditions, Sepp1c/c/alb-cre+/− mice accumulated selenium in the liver at the expense of extra-hepatic tissues, severely worsening clinical manifestations of dietary selenium deficiency. These findings are consistent with there being competition for metabolically available hepatocyte selenium between the synthesis of selenoproteins and the synthesis of selenium excretory metabolites. In addition, selenium deficiency down-regulated the mRNA of the most abundant hepatic selenoprotein, glutathione peroxidase-1 (Gpx1), to 15% of the selenium-replete value, while reducing Sepp1 mRNA, the most abundant hepatic selenoprotein mRNA, only to 61%. This strongly suggests that Sepp1 synthesis is favored in the liver over Gpx1 synthesis when selenium supply is limited, directing hepatocyte selenium to peripheral tissues in selenium deficiency. We conclude that production of Sepp1 by hepatocytes is central to selenium homeostasis in the organism because it promotes retention of selenium in the body and effects selenium distribution from the liver to extra-hepatic tissues, especially under selenium-deficient conditions.
Background: Sepp1 transports selenium, but its complete role in selenium homeostasis is not known.
Results: Deletion of Sepp1 in hepatocytes increases liver selenium at the expense of other tissues and decreases whole-body selenium by increasing excretion.
Conclusion: Sepp1 production by hepatocytes retains selenium in the organism and distributes it from the liver to peripheral tissues.
Significance: Sepp1 is central to selenium homeostasis.
Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in ...humans.
This study aimed to elucidate the human metabolism of selenium to TMSe.
Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status median urinary selenium (U-Se): 6.4 μg/L in mothers, 14 μg/L in children and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 μg/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction.
TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted ∼10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-μg U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts.
There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.
Selenium is an essential immunonutrient which holds the human’s metabolic activity with its chemical bonds. The organic forms of selenium naturally present in human body are selenocysteine and ...selenoproteins. These forms have a unique way of synthesis and translational coding. Selenoproteins act as antioxidant warriors for thyroid regulation, male-fertility enhancement, and anti-inflammatory actions. They also participate indirectly in the mechanism of wound healing as oxidative stress reducers. Glutathione peroxidase (GPX) is the major selenoprotein present in the human body, which assists in the control of excessive production of free radical at the site of inflammation. Other than GPX, other selenoproteins include selenoprotein-S that regulates the inflammatory cytokines and selenoprotein-P that serves as an inducer of homeostasis. Previously, reports were mainly focused on the cellular and molecular mechanism of wound healing with reference to various animal models and cell lines. In this review, the role of selenium and its possible routes in translational decoding of selenocysteine, synthesis of selenoproteins, systemic action of selenoproteins and their indirect assimilation in the process of wound healing are explained in detail. Some of the selenium containing compounds which can acts as cancer preventive and therapeutics are also discussed. These compounds directly or indirectly exhibit antioxidant properties which can sustain the intracellular redox status and these activities protect the healthy cells from reactive oxygen species induced oxidative damage. Although the review covers the importance of selenium/selenoproteins in wound healing process, still some unresolved mystery persists which may be resolved in near future.
Graphic abstract
Selenoprotein P (Sepp1) is a secreted protein that is made up of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains ...the other 9 selenocysteines. Sepp1 isoforms of varying lengths occur but quantitation of them has not been achieved. Hepatic synthesis of Sepp1 affects whole-body selenium content and the liver is the source of most plasma Sepp1. ApoER2, a member of the lipoprotein receptor family, binds Sepp1 and facilitates its uptake into the testis and retention of its selenium by the brain. Megalin, another lipoprotein receptor, facilitates uptake of filtered Sepp1 into proximal tubule cells of the kidney. Thus, Sepp1 serves in homeostasis and distribution of selenium. Mice with deletion of Sepp1 suffer greater morbidity and mortality from infection with
Trypanosoma congolense than do wild-type mice. Mice that express only the N-terminal domain of Sepp1 have the same severity of illness as wild-type mice, indicating that the protective function of Sepp1 against the infection resides in the N-terminal (redox) domain. Thus, Sepp1 has several functions. In addition, plasma Sepp1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status.
Selenium concentrations in the soil environment are directly linked to its transfer in the food chain, eventually causing either deficiency or toxicity associated with several physiological ...dysfunctions in animals and humans. Selenium bioavailability depends on its speciation in the soil environment, which is mainly influenced by the prevailing pH, redox potential, and organic matter content of the soil. The selenium cycle in the environment is primarily mediated through chemical and biological selenium transformations. Interactions of selenium with microorganisms and plants in the soil environment have been studied in order to understand the underlying interplay of selenium conversions and to develop environmental technologies for efficient bioremediation of seleniferous soils. In situ approaches such as phytoremediation, soil amendment with organic matter and biovolatilization are promising for remediation of seleniferous soils. Ex situ remediation of contaminated soils by soil washing with benign leaching agents is widely considered for removing heavy metal pollutants. However, it has not been applied until now for remediation of seleniferous soils. Washing of seleniferous soils with benign leaching agents and further treatment of Se-bearing leachates in bioreactors through microbial reduction will be advantageous as it is aimed at removal as well as recovery of selenium for potential re-use for agricultural and industrial applications. This review summarizes the impact of selenium deficiency and toxicity on ecosystems in selenium deficient and seleniferous regions across the globe, and recent research in the field of bioremediation of seleniferous soils.
Selenium (Se) is an indispensable trace element required for animals and human beings, whereas Se-deficiency can accelerate the development of acute gastric injury induced by over-consumption of ...alcohol. Selenium nanoparticles (SeNPs), as a special Se-supplement with favorable properties and unique bioactivities, are expected to play a passive role in gastroprotection. To the best of our knowledge, the gastroprotective potential of SeNPs is unknown and also, a rapid preparation of orally stable SeNPs available for prospective commercial application in the clinic is needed. Thus, SeNPs-embedded chitosan microspheres (SeNPs-CM) were developed to deliver SeNPs, and their gastroprotective potential was evaluated.
Herein, a rapid, eco-friendly and economic preparation process, composed of synthesis of SeNPs decorated by chitosan (CS), purification of CS-SeNPs by ultra-filtration (UF) and spray-drying of the purified CS-SeNPs, was introduced to prepare SeNPs-CM. The uniformly distributed SeNPs with a nanosize range of 60 nm were loaded into CS-microspheres, and they could be released from the microspheres in gastric conditions. In addition, SeNPs-CM were safer than selenite in terms of Se dose, with a LD
of around 8-fold of that of selenite, and it could efficiently enhance the Se retention in Se-deficient Wistar rats. Furthermore, SeNPs-CM pre-treatment might significantly attenuate the ethanol-induced gastric mucosal damage, based on histological evaluation. It might be partly attributed to the systematic antioxidant activities of SeNPs-CM, reflected by the reduction in lipid peroxidation, the augmentation in antioxidant enzymatic activity as well as decreasing aggressive nitric oxides (NO).
SeNPs-CM could be taken into consideration as a prospective Se-supplement for the oral delivery of SeNPs, with prominent gastroprotective effect against ethanol-induced mucosal injury.
Microbial bio-transformations of the essential trace element selenium are now recognized to occur among a wide variety of microorganisms. These transformations are used to convert this element into ...its assimilated form of selenocysteine, which is at the active center of a number of key enzymes, and to produce selenium nanoparticles, quantum dots, metal selenides, and methylated selenium species that are indispensable for biotechnological and bioremediation applications. The focus of this review is to present the state-of-the-art of all aspects of the investigations into the bacterial transformations of selenium species, and to consider the characterization and biotechnological uses of these transformations and their products.
Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy ...might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.
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BackgroundDespite selenium's toxicity in plants at higher levels, crops supply most of the essential dietary selenium in humans. In plants, inorganic selenium can be assimilated into selenocysteine, ...which can replace cysteine in proteins. Selenium toxicity in plants has been attributed to the formation of non-specific selenoproteins. However, this paradigm can be challenged now that there is increasingly abundant evidence suggesting that selenium-induced oxidative stress also contributes to toxicity in plants.ScopeThis Botanical Briefing summarizes the evidence indicating that selenium toxicity in plants is attributable to both the accumulation of non-specific selenoproteins and selenium-induced oxidative stress. Evidence is also presented to substantiate the claim that inadvertent selenocysteine replacement probably impairs or misfolds proteins, which supports the malformed selenoprotein hypothesis. The possible physiological ramifications of selenoproteins and selenium-induced oxidative stress are discussed.ConclusionsMalformed selenoproteins and oxidative stress are two distinct types of stress that drive selenium toxicity in plants and could impact cellular processes in plants that have yet to be thoroughly explored. Although challenging, deciphering whether the extent of selenium toxicity in plants is imparted by selenoproteins or oxidative stress could be helpful in the development of crops with fortified levels of selenium.
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