Determination of copper status by five biomarkers in serum of healthy women.

BACKGROUND: The essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. OBJECTIVES: The aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. METHOD AND MAIN FINDINGS: This observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. CONCLUSIONS: This study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.

Postprandial Micronutrient Variability and Bioavailability: An Interventional Meal Study in Young vs. Old Participants.

This study explores age- and time-dependent variations in postprandial micronutrient absorption after a micronutrient-rich intervention meal within the Biomiel (bioavailability of micronutrients in elderly) study. Comprising 43 healthy participants, the study compares young (n = 21; mean age 26.90 years) and old (n = 22; mean age 66.77 years) men and women, analyzing baseline concentrations and six-hour postprandial dynamics of iron (Fe), copper (Cu), zinc (Zn), selenium (Se), iodine (I), free zinc (fZn), vitamin C, retinol, lycopene, ß-carotene, α-tocopherol, and γ-tocopherol, along with 25(OH) vitamin D (quantified only at baseline). Methodologically, quantifications in serum or plasma were performed at baseline and also at 90, 180, 270, and 360 min postprandially. Results reveal higher baseline serum Zn and plasma lycopene concentrations in the young group, whereas Cu, Se, Cu/Zn ratio, 25(OH) vitamin D, α-tocopherol, and γ-tocopherol were higher in old participants. Postprandial variability of Zn, vitamin C, and lycopene showed a strong time-dependency. Age-related differences in postprandial metabolism were observed for Se, Cu, and I. Nevertheless, most of the variance was explained by individuality. Despite some limitations, this study provides insights into postprandial micronutrient metabolism (in serum/plasma), emphasizing the need for further research for a comprehensive understanding of this complex field. Our discoveries offer valuable insights for designing targeted interventions to address and mitigate micronutrient deficiencies in older adults, fostering optimal health and well-being across the lifespan.

Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum.

The ageing process is associated with alterations of systemic trace element (TE) homeostasis increasing the risk, e.g. neurodegenerative diseases. Here, the impact of long-term modulation of dietary intake of copper, iron, selenium, and zinc was investigated in murine cerebellum. Four- and 40-wk-old mice of both sexes were supplied with different amounts of those TEs for 26 wk. In an adequate supply group, TE concentrations were in accordance with recommendations for laboratory mice while suboptimally supplied animals received only limited amounts of copper, iron, selenium, and zinc. An additional age-adjusted group was fed selenium and zinc in amounts exceeding recommendations. Cerebellar TE concentrations were measured by inductively coupled plasma-tandem mass spectrometry. Furthermore, the expression of genes involved in TE transport, DNA damage response, and DNA repair as well as selected markers of genomic stability [8-oxoguanine, incision efficiency toward 8-oxoguanine, 5-hydroxyuracil, and apurinic/apyrimidinic sites and global DNA (hydroxy)methylation] were analysed. Ageing resulted in a mild increase of iron and copper concentrations in the cerebellum, which was most pronounced in the suboptimally supplied groups. Thus, TE changes in the cerebellum were predominantly driven by age and less by nutritional intervention. Interestingly, deviation from adequate TE supply resulted in higher manganese concentrations of female mice even though the manganese supply itself was not modulated. Parameters of genomic stability were neither affected by age, sex, nor diet. Overall, this study revealed that suboptimal dietary TE supply does not substantially affect TE homeostasis in the murine cerebellum.

Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P.

Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson's disease. Accordingly, SELENOP levels were low in serum of Wilson's disease patients and Wilson's rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain.

Se supplementation to an in vitro blood-brain barrier does not affect Cu transfer into the brain.

BACKGROUND: Dyshomeostasis of copper (Cu) accompanied by Cu accumulation in certain brain areas has been associated with neurodegenerative diseases. One proposed toxic mode of action following Cu overload is oxidative stress associated with neuronal damage, whereas Selenium (Se) is assumed to play here a protective role. This study investigates the relationship between adequate Se supplementation and the respective consequences for Cu transfer into the brain applying an in vitro model of the blood-brain barrier (BBB). METHODS: Primary porcine brain capillary endothelial cells (PBCECs) seeded on Transwell® inserts were supplemented with selenite starting at cultivation in both compartments. After apical application of 15 or 50 µM CuSO4, transfer of Cu to the basolateral compartment, the brain facing side, was assessed by ICP-MS/MS. RESULTS: Incubation with Cu did not negatively affect the barrier properties, whereas Se had a positive effect. Additionally, Se status improved after selenite supplementation. Transfer of Cu was not affected by selenite supplementation. Under Se-deficient conditions, Cu permeability coefficients decreased with increasing Cu concentrations. CONCLUSION: The results of this study do not indicate that under suboptimal Se supplementation more Cu transfers across the BBB to the brain.

Selenium homeostasis in human brain cells: Effects of copper (II) and Se species.

BACKGROUND: Both essential trace elements selenium (Se) and copper (Cu) play an important role in maintaining brain function. Homeostasis of Cu, which is tightly regulated under physiological conditions, seems to be disturbed in Alzheimer´s (AD) and Parkinson´s disease (PD) patients. Excess Cu promotes the formation of oxidative stress, which is thought to be a major cause for development and progression of neurological diseases (NDs). Most selenoproteins exhibit antioxidative properties and may counteract oxidative stress. However, expression of selenoproteins is altered under conditions of Se deficiency. Serum Se levels are decreased in AD and PD patients suggesting Se as an important factor in the development and progression of NDs. The aim of this study was to elucidate the interactions between Cu and Se in human brain cells particularly with respect to Se homeostasis. METHODS: Firstly, modulation of Se status by selenite or SeMet were assessed in human astrocytes and human differentiated neurons. Therefore, cellular total Se content, intra- and extracellular selenoprotein P (SELENOP) content, and glutathione peroxidase (GPX) activity were quantified. Secondly, to investigate the impact of Cu on these markers, cells were exposed to copper(II)sulphate (CuSO4) for 48 h. In addition, putative protective effects of Se on Cu-induced toxicity, as measured by cell viability, DNA damage, and neurodegeneration were investigated. RESULTS: Modulation of cellular Se status was strongly dependent on Se species. In detail, SeMet increased total cellular Se and SELENOP content, whereas selenite led to increased GPX activity and SELENOP excretion. Cu treatment resulted in 133-fold higher cellular Cu concentration with a concomitant decrease in Se content. Additionally, SELENOP excretion was suppressed in both cell lines, while GPX activity was diminished only in astrocytes. These effects of Cu could be partially prevented by the addition of Se depending on the cell line and Se species used. While Cu-induced oxidative DNA damage could not be prevented by addition of Se regardless of chemical species, SeMet protected against neurite network degeneration triggered by Cu. CONCLUSION: Cu appears to negatively affect Se status in astrocytes and neurons. Especially with regard to an altered homeostasis of those trace elements during aging, this interaction is of high physiological relevance. Increasing Cu concentrations associated with decreased selenoprotein expression or functionality might be a promoting factor for the development of NDs.

The Nutritional Supply of Iodine and Selenium Affects Thyroid Hormone Axis Related Endpoints in Mice.

Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones but additional trace elements such as iron, zinc, and copper are also involved. To compare the primary effects of inadequate intake of selenium and iodine on the thyroid gland, as well as the target organs of thyroid hormones such as liver and kidney, mice were subjected to an eight-week dietary intervention with low versus adequate selenium and iodine supply. Analysis of trace element levels in serum, liver, and kidney demonstrated a successful intervention. Markers of the selenium status were unaffected by the iodine supply. The thyroid gland was able to maintain serum thyroxine levels even under selenium-deficient conditions, despite reduced selenoprotein expression in liver and kidney, including deiodinase type 1. Thyroid hormone target genes responded to the altered selenium and iodine supply, whereas the iron, zinc, and copper homeostasis remained unaffected. There was a notable interaction between thyroid hormones and copper, which requires further clarification. Overall, the effects of an altered selenium and iodine supply were pronounced in thyroid hormone target tissues, but not in the thyroid gland.

Ageing-associated effects of a long-term dietary modulation of four trace elements in mice.

Trace elements (TEs) are essential for diverse processes maintaining body function and health status. The complex regulation of the TE homeostasis depends among others on age, sex, and nutritional status. If the TE homeostasis is disturbed, negative health consequences can result, e.g., caused by impaired redox homeostasis and genome stability maintenance. Based on age-related shifts in TEs which have been described in mice well-supplied with TEs, we aimed to understand effects of a long-term feeding with adequate or suboptimal amounts of four TEs in parallel. As an additional intervention, we studied mice which received an age-adapted diet with higher concentrations of selenium and zinc to counteract the age-related decline of both TEs. We conducted comprehensive analysis of diverse endpoints indicative for the TE and redox status, complemented by analysis of DNA (hydroxy)methylation and markers denoting genomic stability maintenance. TE concentrations showed age-specific alterations which were relatively stable and independent of their nutritional supply. In addition, hepatic DNA hydroxymethylation was significantly increased in the elderly mice and markers indicative for the redox status were modulated. The reduced nutritional supply with TEs inconsistently affected their status, with most severe effects regarding Fe deficiency. This may have contributed to the sex-specific differences observed in the alterations related to the redox status and DNA repair activity. Overall, our results highlight the complexity of factors impacting on the TE status and its physiological consequences. Alterations in TE supply, age, and sex proved to be important determinants that need to be taken into account when considering TE interventions for improving general health and supporting convalescence in the clinics.

Variability in Macro- and Micronutrients of 15 Commercially Available Microalgae Powders.

The nutrient composition of 15 commercially available microalgae powders of Arthrospira platensis, Chlorella pyrenoidosa and vulgaris, Dunaliella salina, Haematococcus pluvialis, Tetraselmis chuii, and Aphanizomenon flos-aquae was analyzed. The Dunaliella salina powders were characterized by a high content of carbohydrates, saturated fatty acids (SFAs), omega-6-polyunsaturated fatty acids (n6-PUFAs), heavy metals, and α-tocopherol, whereas the protein amounts, essential amino acids (EAAs), omega-3-PUFAs (n3-PUFAs), vitamins, and minerals were low. In the powder of Haematococcus pluvialis, ten times higher amounts of carotenoids compared to all other analyzed powders were determined, yet it was low in vitamins D and E, protein, and EAAs, and the n6/n3-PUFAs ratio was comparably high. Vitamin B12, quantified as cobalamin, was below 0.02 mg/100 g dry weight (d.w.) in all studied powders. Based on our analysis, microalgae such as Aphanizomenon and Chlorella may contribute to an adequate intake of critical nutrients such as protein with a high content of EAAs, dietary fibers, n3-PUFAs, Ca, Fe, Mg, and Zn, as well as vitamin D and E. Yet, the nutritional value of Aphanizomenon flos-aquae was slightly decreased by high contents of SFAs. The present data show that microalgae are rich in valuable nutrients, but the macro- and micronutrient profiles differ strongly between and within species.

A matter of concern - Trace element dyshomeostasis and genomic stability in neurons.

Neurons are post-mitotic cells in the brain and their integrity is of central importance to avoid neurodegeneration. Yet, the inability of self-replenishment of post-mitotic cells results in the need to withstand challenges from numerous stressors during life. Neurons are exposed to oxidative stress due to high oxygen consumption during metabolic activity in the brain. Accordingly, DNA damage can occur and accumulate, resulting in genome instability. In this context, imbalances in brain trace element homeostasis are a matter of concern, especially regarding iron, copper, manganese, zinc, and selenium. Although trace elements are essential for brain physiology, excess and deficient conditions are considered to impair neuronal maintenance. Besides increasing oxidative stress, DNA damage response and repair of oxidative DNA damage are affected by trace elements. Hence, a balanced trace element homeostasis is of particular importance to safeguard neuronal genome integrity and prevent neuronal loss. This review summarises the current state of knowledge on the impact of deficient, as well as excessive iron, copper, manganese, zinc, and selenium levels on neuronal genome stability.

Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis.

SCOPE: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. METHODS AND RESULTS: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. CONCLUSIONS: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.

Trace element profile and incidence of type 2 diabetes, cardiovascular disease and colorectal cancer: results from the EPIC-Potsdam cohort study.

PURPOSE: We aimed to examine the prospective association between manganese, iron, copper, zinc, iodine, selenium, selenoprotein P, free zinc, and their interplay, with incident type 2 diabetes (T2D), cardiovascular disease (CVD) and colorectal cancer (CRC). METHODS: Serum trace element (TE) concentrations were measured in a case-cohort study embedded within the EPIC-Potsdam cohort, consisting of a random sub-cohort (n = 2500) and incident cases of T2D (n = 705), CVD (n = 414), and CRC (n = 219). TE patterns were investigated using principal component analysis. Cox proportional hazard models were fitted to examine the association between TEs with T2D, CVD and CRC incidence. RESULTS: Higher manganese, zinc, iodine and selenium were associated with an increased risk of developing T2D (HR Q5 vs Q1: 1.56, 1.09-2.22; HR per SD, 95% CI 1.18, 1.05-1.33; 1.09, 1.01-1.17; 1.19, 1.06-1.34, respectively). Regarding CVD, manganese, copper and copper-to-zinc ratio were associated with an increased risk (HR per SD, 95% CI 1.13, 1.00-1.29; 1.22, 1.02-1.44; 1.18, 1.02-1.37, respectively). The opposite was observed for higher selenium-to-copper ratio (HR Q5 vs Q1, 95% CI 0.60, 0.39-0.93). Higher copper and zinc were associated with increasing risk of developing CRC (HR per SD, 95% CI 1.29, 1.05-1.59 and 1.14, 1.00-1.30, respectively). Selenium, selenoprotein P and selenium-to-copper-ratio were associated to decreased risk (HR per SD, 95% CI 0.82, 0.69-0.98; 0.81, 0.72-0.93; 0.77, 0.65-0.92, respectively). Two TE patterns were identified: manganese-iron-zinc and copper-iodine-selenium. CONCLUSION: Different TEs were associated with the risk of developing T2D, CVD and CRC. The contrasting associations found for selenium with T2D and CRC point towards differential disease-related pathways.

Vitamin and Mineral Status in a Vegan Diet.

BACKGROUND: In Germany, public interest in a vegan diet is steadily growing. There are, however, no current data on the macro- and micronutrient status of vegans. METHODS: In a cross-sectional study entitled "The Risks and Benefits of a Vegan Diet" (RBVD), we investigated the dietary intake, basic laboratory parameters, vitamin status, and trace-element status of 36 vegans and 36 persons on an omnivorous diet. Each group consisted of 18 men and 18 women aged 30-60. RESULTS: Nearly all the vegans and one-third of the persons on a mixed diet had consumed supplements in the previous 4 weeks. Vegans and nonvegans had similar energy intake but differed in the intake of both macronutrients (e.g., dietary fiber) and micronutrients (e.g., vitamins B12, B2, D, E, and K, as well as folate, iodine, and iron). There were no intergroup differences in the biomarkers of vitamin B12, vitamin D, or iron status. The ferritin values and blood counts indicated iron deficiency in four vegans and three non-vegans. Measurements in 24-hour urine samples revealed lower calcium excretion and markedly lower iodine excretion in vegans compared to non-vegans; in one-third of the vegans, iodine excretion was lower than the WHO threshold value (<20 µg/L) for severe iodine deficiency. CONCLUSION: Vitamin B12 status was similarly good in vegans and non-vegans, even though the vegans consumed very little dietary B12. This may be due to the high rate of supplementation. The findings imply a need to also assure adequate iodine intake in the population, especially among persons on a vegan diet.

Copper interferes with selenoprotein synthesis and activity.

Selenium and copper are essential trace elements for humans, needed for the biosynthesis of enzymes contributing to redox homeostasis and redox-dependent signaling pathways. Selenium is incorporated as selenocysteine into the active site of redox-relevant selenoproteins including glutathione peroxidases (GPX) and thioredoxin reductases (TXNRD). Copper-dependent enzymes mediate electron transfer and other redox reactions. As selenoprotein expression can be modulated e.g. by H2O2, we tested the hypothesis that copper status affects selenoprotein expression. To this end, hepatocarcinoma HepG2 cells and mice were exposed to a variable copper and selenium supply in a physiologically relevant concentration range, and transcript and protein expression as well as GPX and TXNRD activities were compared. Copper suppressed selenoprotein mRNA levels of GPX1 and SELENOW, downregulated GPX and TXNRD activities and decreased UGA recoding efficiency in reporter cells. The interfering effects were successfully suppressed by applying the copper chelators bathocuproinedisulfonic acid or tetrathiomolybdate. In mice, a decreased copper supply moderately decreased the copper status and negatively affected hepatic TXNRD activity. We conclude that there is a hitherto unknown interrelationship between copper and selenium status, and that copper negatively affects selenoprotein expression and activity most probably via limiting UGA recoding. This interference may be of physiological relevance during aging, where a particular shift in the selenium to copper ratio has been reported. An increased concentration of copper in face of a downregulated selenoprotein expression may synergize and negatively affect the cellular redox homeostasis contributing to disease processes.

Functional Biomarkers for the Selenium Status in a Human Nutritional Intervention Study.

Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se.

Changes of trace element status during aging: results of the EPIC-Potsdam cohort study.

PURPOSE: We aimed to evaluate age-dependent changes of six trace elements (TE) [manganese (Mn), iron (Fe), zinc (Zn), copper (Cu), iodine (I), and selenium (Se)] over a 20-year period. METHODS: TE concentrations were determined using repeated serum samples taken at baseline and after 20 years of follow-up from 219 healthy participants of the EPIC-Potsdam study, using inductively coupled plasma tandem mass spectrometry. For each TE, absolute and relative differences were calculated between the two time points, as well as the proportion of individuals within normal reference ranges. Interdependence between age-related TE differences was investigated using principal component analysis (PCA). Relationships between selected factors (lifestyle, sociodemographic, anthropometric factors, and hypertension) and corresponding TE longitudinal variability were examined using multivariable linear regression models. RESULTS: Median age of our study sample was 58.32 years (4.42) at baseline and 40% were females. Median Mn, Zn, Se concentrations and Se to Cu ratio significantly decreased during aging while median Fe, Cu, I concentrations and Cu to Zn ratio significantly increased. A substantial percentage of the participants, at both time points, had Zn concentrations below the reference range. The first PCA-extracted factor reflected the correlated decline in both Mn and Zn over time while the second factor reflected the observed (on average) increase in both Cu and I over time. Overall, none of the investigated factors were strong determinants of TE longitudinal variability, except possibly dietary supplement use, and alcohol use for Fe. CONCLUSIONS: In conclusion, in this population-based study of healthy elderly, decrease in Mn, Zn, and Se concentrations and increase in Fe, Cu, and I concentrations were observed over 20 years of follow-up. Further research is required to investigate dietary determinants and markers of TE status as well as the relationships between TE profiles and the risk of age-related diseases.

Cross-sectional analysis of trace element status in thyroid disease.

BACKGROUND: The 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. OBJECTIVE: Assessment of trace element status in thyroid patients in a European metropolis. MATERIAL AND METHODS: Adult 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. RESULTS: The 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. CONCLUSIONS: In 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.

Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper.

Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice.

A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS.

In order to assess the individual trace element status of humans for either medical or scientific purposes, amongst others, blood serum levels are determined. Furthermore, animal models are used to study interactions of trace elements. Most published methods require larger amounts (500-1000 µL) of serum to achieve a reliable determination of multiple trace elements. However, oftentimes, these amounts of serum cannot be dedicated to a single analysis and the amount available for TE-determination is much lower. Therefore, a published ICP-MS/MS method for trace element determination in serum was miniaturized, optimized and validated for the measurement of Mn, Fe, Cu Zn, I and Se in as little as 50 µL of human and murine serum and is presented in this work. For validation, recoveries of multiple LOTs and levels from commercially available human reference serum samples were determined, intra- and inter-day variations were assessed and limits of detection and quantification determined. It is shown, that the method is capable of giving accurate and reproducible results for all six elements within the relevant concentration ranges for samples from humans living in central Europe as well as from laboratory mice. As a highlight, the achieved limits of detection and quantification for Mn were found to be at 0.02 µg/L serum and 0.05 µg/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine.

Treatment of Caenorhabditis elegans with Small Selenium Species Enhances Antioxidant Defense Systems.

SCOPE: Small selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo. METHODS AND RESULTS: In the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data. CONCLUSION: Se species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake.