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.     

Cross-sectional analysis of trace element status in thyroid disease

BackgroundThe synthesis of thyroid hormone depends on a set of trace elements, most importantly selenium and iodine. The dietary supply with certain micronutrients is limited in many areas of the world, including central Europe and large parts of Asia and Africa. Moreover, both thyroid disease risk and therapy effects are modulated by trace element supply and status.ObjectiveAssessment of trace element status in thyroid patients in a European metropolis.Material and MethodsAdult patients visiting a medical praxis in Berlin, Germany, were enrolled into a cross-sectional analysis, and serum samples were obtained from thyroid patients (n = 323) with different conditions including goitre, hypothyroidism, malignancy or autoimmune thyroid disease. Trace elements (iodine, selenium, copper and zinc) were assessed by ICP-MS/MS or total reflection X-ray analysis, along with two protein biomarkers of selenium status (selenoprotein P, glutathione peroxidase), and compared to the clinical phenotype.ResultsThe patients displayed relatively low serum zinc and selenium concentrations as compared to a set (n = 200) of healthy subjects (zinc; 1025+/-233 vs. 1068+/−230 μg/L, p < 0.01, selenium; 76.9+/18.8 vs. 85.1+/−17.4 μg/L, p < 0.0001). A high fraction of patients (37.5%) was classified as selenium-deficient (serum selenium concentrations <70 μg/L), in particular the patients with thyroid malignancy (59%). Serum copper was not different between the groups, and total serum iodine concentrations were unrelated to thyroid disease. Explorative statistical analyses yielded no significant interactions between the trace elements and disease parameters, except for free thyroxine inversely correlating to the copper/selenium ratio.ConclusionsIn adult thyroid patients, there is no relation of circulating copper, iodine, selenium or zinc concentrations to thyroid hormone. However, a large fraction of German thyroid patients displays a considerable selenium deficit, known to constitute a disease risk potentially impairing convalescence and aggravating autoimmune disease processes. It appears advisable to testing thyroid patients for selenium deficiency, and once diagnosed, an increased supply via dietary counselling or active supplementation should be considered.     

Exploring the role of copper and selenium in the maintenance of normal thyroid function among healthy Koreans

BackgroundSelenium and iodine are trace elements well known to have important roles in the synthesis and metabolism of thyroid hormones. However, the effects of other trace elements on thyroid hormones are still inconclusive. We investigated the association between several trace elements and thyroid hormones.MethodsThe data of 448 subjects who were measured for both, trace elements and TSH/free T4, at the Heath Checkup Center were retrospectively reviewed. The presence of thyroiditis (from thyroid echogenicity) and thyroid nodules were reviewed in the subjects who underwent thyroid ultrasonography.ResultsBlood concentrations of manganese, copper, selenium, and molybdenum were associated with TSH or free T4. After adjusting for age, sex, BMI, smoking, and alcohol consumption, blood copper levels were positively associated with free T4 in both sexes and selenium levels were positively associated with free T4 in women. There was no association between trace elements and thyroiditis. Blood copper concentration had a weak non-linear association with the presence of thyroid nodules.ConclusionsThis study demonstrated that blood concentrations of copper and selenium were significantly associated with free T4 in healthy Korean subjects with sufficient iodine intake suggesting their role in maintaining normal thyroid function.     

Does selenium fortification of kale and kohlrabi sprouts change significantly their biochemical and cytotoxic properties?

BackgroundThe sprouts of Brassica vegetables are known from their nutritional and chemopreventive values. Moreover, sprouts fortification with some trace elements, like selenium, may increase their importance in human diet. Thus, the aim of our study was to examine if selenium enrichment of kale and kohlrabi sprouts may influence their biochemical properties (phenolic acids and L-tryptophan content, antioxidant potential) or cytotoxic activity. Additional aim of the study was to evaluate the profile of selenium compounds and to describe the multidimensional interactions between the mentioned parameters.MethodsSelenium content in the sprouts was evaluated by double-channel atomic fluorescence spectrometer AFS-230 with the flow hydride-generation system. Separation of selenium species in water soluble fraction was performed by size-exclusion LC-ICP-MS. The identification and quantification of phenolic acids and L-tryptophan was performed by HPLC. For antioxidant activity DPPH and FRAP methods were used. Cytotoxic activity of the sprouts extracts on a panel of human metastatic carcinoma cells was evaluated by MTT test.ResultsSelenium content in the fortified sprouts was several orders of magnitude higher than in the unfortified ones. Only small percentage of supplemented selenium (ca. 10 %) was incorporated into the sprouts as seleno-L-methionine, while the other detected selenium species remained unidentified. Selenium fortification differently stimulated the production of phenolic acids (sinapic, chlorogenic, isochlorogenic and caffeic acid) in the tested sprouts, depending on the particular species, selenium dose and the investigated compound. PCA analysis revealed strong correlation between antioxidant parameters and phenolic acids and L-tryptophan, while Se correlated only with caffeic acid. The sprouts extracts (≥1 mg/mL) showed cytotoxic potency to all the studied cancer cell lines (SW480, SW620, HepG2, SiHa), regardless the selenium supplementation.ConclusionSe-fortified kale and kohlrabi sprouts are good candidates for functional food ingredients. Moreover, these results indicate that the sprouts enriched with sodium selenite show higher nutritional value, without significant changes in their cytotoxic activity.     

Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis,a mechanistic view

BackgroundMitochondria, the power plants of the cell, are known as a cross-road of different cellular signaling pathways. These cytoplasmic double-membraned organelles play a pivotal role in energy metabolism and regulate calcium flux in the cells. It is well known that mitochondrial dysfunction is associated with different diseases such as neurodegeneration and cancer. A growing body of literature has shown that polyphenolic compounds exert direct effects on mitochondrial ultra-structure and function. Resveratrol is known as one of the most common bioactive constituents of red wine, which improves mitochondrial functions under in vitro and in vivo conditions.Scope of reviewThis paper aims to review the molecular pathways underlying the beneficial effects of resveratrol on mitochondrial structure and functions. In addition, we discuss the chemistry and main sources of resveratrol.Major conclusionsResveratrol represents the promising effects on mitochondria in different experimental models. However, there are several reports on the detrimental effects elicited by resveratrol on mitochondria.General significanceAn understanding of the chemistry and source of resveratrol, its bioavailability and the promising effects on mitochondria brings a new hope to therapy of mitochondrial dysfunction-related diseases.     

Acute human toxicity and mortality after selenium ingestion: A review

BackgroundAlthough selenium is an essential element for humans, acute toxicity has been reported after high oral exposure.MethodsThe published literature on the acute toxicity of oral selenium was gathered and reviewed.ResultsReported symptoms and signs include abdominal symptoms, such as vomiting, diarrhea, pain, and nausea, as well as garlic-like odor on the breath. In cases of severe toxicity, cardiac and pulmonary symptoms may develop and ultimately lead to mortality. Mortality has been described after the ingestion of gun bluing solutions, which often contain selenous acid among other potentially toxic substances. Mortality has also been reported after the ingestion of other forms of selenium. Ingested doses associated with mortality are in the range of 1–100 mg Se/kg body weight. Blood levels associated with mortality are above 300 μg Se/L (normal level: 100 μg/L), whereas urinary levels associated with the same endpoint are above170 μg Se/L (normal level: 20–90 μg/L).ConclusionThe acute toxicity associated with oral selenium ingestion and the blood and urinary levels of selenium in different cases of poisonings were reviewed. Mortality is a risk of acute selenium poisoning. Concentrations of selenium in blood and urine samples in non-fatal cases are close to those observed in fatal cases.     

Effects of boron-containing compounds in the fungal kingdom

BackgroundThe number of known boron-containing compounds (BCCs) is increasing due to their identification in nature and innovative synthesis procedures. Their effects on the fungal kingdom are interesting, and some of their mechanisms of action have recently been elucidated.MethodsIn this review, scientific reports from relevant chemistry and biomedical databases were collected and analyzed.ResultsIt is notable that several BCC actions in fungi induce social and economic benefits for humans. In fact, boric acid was traditionally used for multiple purposes, but some novel synthetic BCCs are effective antifungal agents, particularly in their action against pathogen species, and some were recently approved for use in humans. Moreover, most reports testing BCCs in fungal species suggest a limiting effect of these compounds on some vital reactions.ConclusionsNew BCCs have been synthesized and tested for innovative technological and biomedical emerging applications, and new interest is developing for discovering new strategic compounds that can act as environmental or wood protectors, as well as antimycotic agents that let us improve food acquisition and control some human infections.     

Design,synthesis and biological evaluation of novel inosine 5′-monophosphate dehydrogenase (IMPDH) inhibitors

Abstract

This study is based on our attempts to further explore the structure–activity relationship (SAR) of VX-148 (3) in an attempt to identify inosine 5′-mono-phosphate dehydrogenase (IMPDH) inhibitors superior to mycophenolic acid. A five-point pharmacophore developed using structurally diverse, known IMPDH inhibitors guided further design of novel analogs of 3. Several conventional as well as novel medicinal chemistry strategies were tried. The combined structure- and ligand-based approaches culminated in a few analogs with either retained or slightly higher potency. The compounds which retained the potency were also checked for their ability to inhibit human peripheral blood mononuclear cells proliferation. This study illuminates the stringent structural requirements and strict SAR for IMPDH II inhibition.     

Transglycosylation Reactions of Purine Nucleosides. A Review

Abstract

Mechanism, regio- and stereoselectivity, reversibility as well as some practical applications of transglycosylation reactions in the chemistry of purine nucleosides are reviewed. There are two main reaction pathways of glycosylation and transglycosylation in the purine series; i) the better known and generally accepted 3→9 sequence of adenine and its derivatives ii) the equally conceivable 7?9 mechanism for guanine and other 6-oxopurines, which is hereby supported by the author's study.

     

4,5-Dihydro-1H-pyrazole: an indispensable scaffold

Abstract

Pyrazoles, categorized as nitrogen-containing heterocycles, are well known for their interminable participation in the field of perpetual research and development of therapeutical active agents. As a consequence pyrazoles became an inevitable core of numerous drugs having diverse activities. The broad spectrum of activities portrayed by the pyrazoles instigated the researchers to modify the pyrazole ring as 4,5-dihydro-1H-pyrazoles commonly known as 2-pyrazolines. The present review is a concerted effort to retrace compounds covered from 2009-till date which owe diverse biological activities to the 2-pyrazoline scaffold and also condenses the retro-synthetic approaches employed for their synthesis. This endeavor culminated in revelation that inhibitory potential varied when the substituents in particular N-substituents of 2-pyrazolines were altered.     

Gold nanomaterials as key suppliers in biological and chemical sensing,catalysis, and medicine

BackgroundGold nanoparticles (AuNPs) with unique physicochemical properties have received a great deal of interest in the field of biological, chemical and biomedical implementations. Despite the widespread use of AuNPs in chemical and biological sensing, catalysis, imaging and diagnosis, and more recently in therapy, no comprehensive summary has been provided to explain how AuNPs could aid in developing improved sensing and catalysts systems as well as medical settings.Scope of reviewThe chemistry of Au-based nanosystems was followed by reviewing different applications of Au nanomaterials in biological and chemical sensing, catalysis, imaging and diagnosis by a number of approaches, and finally synergistic combination therapy of different cancers. Afterwards, the clinical impacts of AuNPs, future application of AuNPs, and opportunities and challenges of AuNPs application were also discussed.Major conclusionsAuNPs show exclusive colloidal stability and are considered as ideal candidates for colorimetric detection, catalysis, imaging, and photothermal transducers, because their physicochemical properties can be tuned by adjusting their structural dimensions achieved by the different manufacturing methods.General significanceThis review provides some details about using AuNPs in sensing and catalysis applications as well as promising theranostic nanoplatforms for cancer imaging and diagnosis, and sensitive, non-invasive, and synergistic methods for cancer treatment in an almost comprehensive manner.     

The time-trend and the relation between smoking and circulating selenium concentrations in Norway

ObjectivesThe objectives of this study were to investigate biomarkers of selenium status in relation to smoking habits and to analyze the time-trend of selenium in serum (S-Se) in Norway during the time period 1995–2006.MethodsThe impact of smoking habits was investigated in a population recruited to a cross-sectional study of blue-collar workers in the southern part of the country (n=98). The time-trend was studied in all subjects who delivered blood samples for the determination of S-Se to a large commercial clinical chemistry laboratory in Norway.ResultsSmokers had 0.14 and 0.20 μmol/L lower concentrations of selenium in whole blood (B-Se) and serum, respectively, than non-smokers. The amount of smoking, as assessed by the serum cotinine concentration, was negatively associated with the B-Se concentration (Pearson's r=?0.43). The 1/3 of the blue-collar workers with the lowest concentrations of B-Se or S-Se had lower activity of glutathione peroxidase in serum (S-GSHpx) than the remaining subjects. Snuff users had about the same levels of B-Se and S-Se as the non-smokers, although they had about the same amount of nicotine metabolites in urine and serum as the smokers. A decreasing trend of S-Se was observed during the observation period from 1995 to 2006. The mean concentration was 1.26 μmol/L in 1995, while the lowest mean concentration was measured in 2003 (1.01 μmol/L).ConclusionSmoking, but not snuffing, is associated with lower concentrations of B-Se and S-Se. The reduction of B-Se is negatively associated with the nicotine biomarker cotinine in serum. A substantial proportion of blue-collar workers had not maximized the activity of S-GSHpx. Selenium status may have become poorer since 1995.     

X-ray spectroscopy and imaging of selenium in living systems

Background

Selenium is an essential element with a rich and varied chemistry in living organisms. It plays a variety of important roles ranging from being essential in enzymes that are critical for redox homeostasis to acting as a deterrent for herbivory in hyperaccumulating plants. Despite its importance there are many open questions, especially related to its chemistry in situ within living organisms.

Selenium and vitamin E ameliorate lead acetate-induced hepatotoxicity in rats via suppression of oxidative stress,mRNA of heat shock proteins,and NF-kB production

BackgroundLead exposure results in a terrible rise in heat shock protein levels.ObjectiveThis research was conducted to look at the effects of lead poisoning on heat shock response, oxidative stress, and inflammatory markers in albino rats, as well as the power of selenium and vitamin E to resist lead toxic effects.MethodsEight groups of albino rats are used. Each group contained six rats where the first group represented the negative control, and the other groups were treated with olive oil, vitamin E, selenium, lead, (vitamin E + lead), (selenium + lead), and (vitamin E + selenium + lead). All the treatments lasted for 28 days. Then, the mRNA expression of interested heat shock proteins (HSP90, HSP70, and HSP60) was assessed. For oxidative stress disruption, we investigated nitric oxide (NO) and malondialdehyde (MDA) content, and enzymatic and non-enzymatic antioxidants activity respectively in rat livers.Resultsour results revealed the synergetic protective effect of the combination of two antioxidants (vitamin E and selenium) against lead poising. This was clear in regulating HSPs expression, inflammatory markers, glucose, lipid profile, liver functions, and antioxidant enzymes more than the treatment with one antioxidant.ConclusionPb is a toxic material that can induce HSPs and inflammatory markers expression. Selenium and vitamin E can give excellent effects in ameliorating Pb toxicity when used together.     

Sensory ecology of salps (Tunicata,thaliacea): More questions than answers

There is still relatively little known about the natural history of gelatinous animals in the plankton, and their sensory ecology remains largely a matter of surmise, based on limited morphological, physiological and behavioral data. Pelagic tunicates are among the most widely distributed and abundant of the gelatinous zooplank‐ton, and display a range of behavior that is apparently cued by aspects of their environment. Different kinds of information may be important for different scales of behavior. Feeding and predator avoidance are likely to be affected by near‐field stimuli from visual, chemical or mechanical sources, while far‐field information such as gravity, light, temperature, or pressure are likely to cue behavior spanning larger time and space scales, such as vertical or ontogenetic migration, aggregation and reproductive cycles. A variety of sensory structures have been described in pelagic tunicates, including photoreceptors of varying complexity, and several structures that have been suggested to be mechano‐ or chemoreceptors. Focussing on salps, this paper describes behavior that depends on sensory information, reviews the known structure and function of sensory receptors, and suggests some hypotheses on mechanisms defining the sensory ecology of these planktonic organisms.     

Selenium intake and status of postpartum women and postnatal depression during the first year after childbirth in New Zealand – Mother and Infant Nutrition Investigation (MINI) study

BackgroundSelenium (Se) plays an important role in selenoproteins as an antioxidant, and is involved in thyroid function, mental health and child development. Selenium is low in the local food supplies in NZ. Low selenium intake has been reported in women of childbearing age and postmenopausal women, however, there is little research relating to breastfeeding women and their infants.PurposeThe study investigates maternal and infant selenium intake and status during the first year postpartum, and possible relationships to postnatal depression and anxiety.Basic proceduresThe Mother and Infant Nutrition Investigation (MINI) study is an observational longitudinal cohort study. In total 87 breastfeeding mother-infant pairs were recruited and followed up at 3, 6 and 12 months postpartum. Maternal selenium intake was estimated from a four-day diet diary (4DDD). Selenium concentrations were measured in maternal spot urine, breastmilk and plasma; and infant spot urine samples. Postnatal depression was screened by the Edinburgh Postnatal Depression Scale (EPDS) questionnaire.Main findingsMedian maternal selenium intake was 62 (50, 84) μg/day, with 56 % below the Estimated Average Requirement (EAR) of 65 μg/day. At 3, 6, and 12 months postpartum, median maternal urinary selenium:creatinine ratios were 29.0 (22.4, 42.0), 29.5 (23.1, 28.4), and 30.9 (24.3, 35.3) μg/g; median infant urinary selenium concentrations (IUSC) were 8 (6,13), 11 (6, 15), and 24 (10, 40) μg/L; median breastmilk selenium concentrations (BMSC) were 13 (11, 14), 11 (9, 11) and 12 (11, 13) μg/L; 18 %, 11 % and 14 % of women reported probable minor depression based on the EPDS scores equal or above 10. Estimated median infant selenium intake at 3 and 6 months were 9 (8, 11) and 8 (7, 10) μg/day with 85 % and 93 % below the Adequate Intake of 12 μg/day. Median maternal plasma selenium was 105.8 μg/L at 6 months postpartum. Minor depression at three months postpartum was significantly different across tertiles of plasma selenium concentrations (p = 0.041).Principle conclusionsSuboptimal selenium intake was observed among breastfeeding mothers and their infants in the MINI study. Potentially, some women had insufficient selenium status. Relation between selenium status and risk of postnatal depression and anxiety was inconclusive.Further research is required to explore effects on maternal thyroid function and infant neurodevelopment among women with inadequate selenium intake and status.     

Cytotoxic iron chelators: characterization of the structure,solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (<Emphasis Type="Bold">H</Emphasis>PKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto–enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe^II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.Electronic Supplementary Material Supplementary material is available in the online version of this article at .Abbreviations DFO desferrioxamine - HPKIH di-2-pyridyl ketone isonicotinoyl hydrazone - HNIH 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone - HPCIH 2-pyridinecarbaldehyde isonicotinoyl hydrazone - HPIH pyridoxal isonicotinoyl hydrazone - L linear DNA - OC open circular DNA - SC supercoiled DNA     

The Stumble—From Pipe Cleaner to Bone Builder

ObjectiveTo review the history of the transition of bisphosphonate use from bench chemistry to clinical applications.MethodsPertinent medical literature, including limited-distribution as well as peer-reviewed publications, was reviewed.ResultsBisphosphonates were originally developed to interfere with calcium deposition. An expanded understanding of bone physiology, as well as a growing appreciation of bisphosphonate chemistry, allowed a broadening range of clinical applications.ConclusionThe use of bisphosphonates in clinical medicine depended on a series of fortuitous events that, at the time, were “stumbles,” not unlike the discoveries of Fleming and Newton. The logical sequence is more apparent in retrospect. (Endocr Pract. 2007;13:194-197)     

富硒条件下蜜环菌菌株硒耐受性及胞外酶生物活性的研究

[目的]通过对蜜环菌(Armillaria mellea)的富硒驯化,研究各菌株硒耐受性、有机硒含量及生物活性的变化规律,从而获得生物活性更强的蜜环菌,并对富硒蜜环菌的生物学特征进行初步研究.[方法]以Na2SeO3为无机硒试剂对蜜环菌进行富硒驯化;采用氢化物原子荧光光谱法测定蜜环菌的硒含量,热水浴法测定蜜环菌的无机硒...