TY - JOUR A1 - Maares, Maria A1 - Keil, Claudia A1 - Koza, Jenny A1 - Straubing, Sophia A1 - Schwerdtle, Tanja A1 - Haase, Hajo T1 - In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins JF - International Journal of Molecular Sciences N2 - The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium. KW - intestinal zinc resorption KW - zinc binding KW - mucus layer KW - intestinal mucins KW - in vitro intestinal model KW - goblet cells KW - Caco-2/HT-29-MTX-model Y1 - 2018 U6 - https://doi.org/10.3390/ijms19092662 SN - 1422-0067 VL - 19 IS - 9 ER - TY - JOUR A1 - Duydu, Yalcin A1 - Basaran, Nursen A1 - Aydin, Sevtap A1 - Ustundag, Aylin A1 - Yalcin, Can Özgür A1 - Anlar, Hatice Gul A1 - Bacanli, Merve A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Schwerdtle, Tanja A1 - Werner, Matthias A1 - Meyer, Sören A1 - Bolt, Hermann M. T1 - Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions JF - Archives of toxicology : official journal of EUROTOX N2 - Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 +/- 17.47 (7.95-106.8) mg B/day and 570.6 +/- 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds. KW - Boron exposure KW - Boric acid KW - Reproductive toxicity KW - FSH KW - LH KW - Testosterone KW - Semen parameters Y1 - 2018 U6 - https://doi.org/10.1007/s00204-018-2296-7 SN - 0340-5761 SN - 1432-0738 VL - 92 IS - 10 SP - 3051 EP - 3059 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Alker, Wiebke A1 - Schwerdtle, Tanja A1 - Schomburg, Lutz A1 - Haase, Hajo T1 - A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum JF - International journal of molecular sciences N2 - Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status. KW - zinc KW - free zinc KW - serum KW - biomarker KW - fluorescent probe KW - Zinypr-1 Y1 - 2019 U6 - https://doi.org/10.3390/ijms20164006 SN - 1661-6596 SN - 1422-0067 VL - 20 IS - 16 PB - MDPI CY - Basel ER - TY - JOUR A1 - Witt, Barbara A1 - Ebert, Franziska A1 - Meyer, Sören A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons JF - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology N2 - Scope: In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Methods and results: Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA(V)) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA(V) were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. Conclusion: These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment. KW - Arsenic-containing fatty acids KW - Arsenic-containing hydrocarbons KW - Arsenite KW - Arsenolipids KW - Neurodevelopmental toxicity Y1 - 2017 U6 - https://doi.org/10.1002/mnfr.201700199 SN - 1613-4125 SN - 1613-4133 VL - 61 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Witt, Barbara A1 - Meyer, Sören A1 - Ebert, Franziska A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons JF - Archives of toxicology : official journal of EUROTOX N2 - Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly’s brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized. KW - Arsenolipids KW - Neurons KW - Cytotoxicity KW - Neurotoxicity KW - Arsenic-containing hydrocarbons KW - Arsenic-containing fatty acids Y1 - 2017 U6 - https://doi.org/10.1007/s00204-017-1933-x SN - 0340-5761 SN - 1432-0738 VL - 91 SP - 3121 EP - 3134 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Lossow, Kristina A1 - Schwerdtle, Tanja A1 - Kipp, Anna Patricia T1 - Selen und Jod: essenzielle Spurenelemente für die Schilddrüse T1 - Selenium and iodine - essential trace elements for the thyroid JF - Ernährungs-Umschau : Forschung & Praxis N2 - Selen und Jod sind essenzielle Spurenelemente, die gemeinsam für eine optimale Funktionstüchtigkeit der Schilddrüse erforderlich sind. Der Mangel eines oder beider Elemente führt zu Verschiebungen auf Ebene der Schilddrüsenhormonproduktion mit weitreichenden Konsequenzen für Stoffwechselprozesse, neurologische Entwicklung und Erkrankungen. Auch bei Autoimmunerkrankungen der Schilddrüse spielt die Versorgung mit Jod und Selen eine wichtige Rolle. Als Biomarker für den Selenstatus eignet sich der Gehalt des Gesamtselens oder der des Selenoproteins P im Serum. Zur Bestimmung des Jodstatus wird in der Regel der Jodgehalt im Urin herangezogen. Um den Versorgungszustand an diesen und vier weiteren essenziellen Spurenelementen besser zu erfassen, charakterisiert die Forschungsgruppe TraceAge alters- und geschlechtsspezifische Spurenelementprofile und neue funktionelle Biomarker der einzelnen Spurenelemente. Außerdem sollen Interaktionen weiterer Spurenelemente genauer untersucht werden. N2 - Selenium and iodine are essential trace elements that work together to ensure that the thyroid functions optimally. A deficiency in one or both of these elements leads to fluctuations in thyroid hormone production, which have far-reaching consequences in terms of metabolic processes, neurological development, and disease. Iodine and selenium supply also play an important role in autoimmune diseases of the thyroid. Both the total selenium concentration in the serum and the concentration of selenoprotein P are suitable biomarkers for determining selenium status. Iodine concentration in the urine is the most commonly used method of determining iodine status. In order to improve assessment of supply status for these two essential trace elements plus an additional four, the TraceAge research group is identifying age- and sex-specific trace element profiles as well as new functional biomarkers for the individual trace elements. In addition, the research group will investigate interactions with other trace elements in more detail. KW - Selen KW - Jod KW - Schilddrüse KW - Schilddrüsenautoimmunerkrankungen KW - Selenoproteine KW - TraceAge Y1 - 2019 U6 - https://doi.org/10.4455/eu.2019.032 SN - 0174-0008 VL - 66 IS - 9 SP - M531 EP - M536 PB - Umschau-Zeitschriftenverl. CY - Frankfurt, Main ER - TY - JOUR A1 - Meyer, Sören A1 - Matissek, M. A1 - Müller, Sandra Marie A1 - Taleshi, M. S. A1 - Ebert, Franziska A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - In vitro toxicological characterisation of three arsenic-containing hydrocarbons JF - Metallomics N2 - Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk. KW - cod-liver KW - human-cells KW - arsenolipids present KW - excision-repair KW - fatty-acids KW - marine oils KW - RP-HPLC KW - metabolites KW - identification KW - trivalent Y1 - 2014 U6 - https://doi.org/10.1039/c4mt00061g SN - 1756-591X SN - 1756-5901 VL - 2014 IS - 6 SP - 1023 EP - 1033 ER - TY - JOUR A1 - Unterberg, Marlies A1 - Leffers, Larissa A1 - Hübner, Florian A1 - Humpf, Hans-Ulrich A1 - Lepikhov, Konstantin A1 - Walter, Jörn A1 - Ebert, Franziska A1 - Schwerdtle, Tanja T1 - Toxicity of arsenite and thio-DMAV after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics JF - Toxicology Research N2 - This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies. KW - induced malignant-transformation KW - genomic dna methylation KW - vitro toxicological characterization KW - thio-dimethylarsinic acid KW - bladder-cancer KW - methyltransferases dnmt3a KW - cytosine methylation KW - carcinogen exposure KW - mass-spectrometry KW - gene-expression Y1 - 2014 SN - 2045-4538 SN - 2045-452X VL - 3 IS - 6 SP - 456 EP - 464 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Meyer, S. A1 - Raber, G. A1 - Ebert, Franziska A1 - Leffers, L. A1 - Müller, Sandra Marie A1 - Taleshi, M. S. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites JF - Toxicology research N2 - Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids. Y1 - 2015 U6 - https://doi.org/10.1039/c5tx00122f SN - 2045-4538 VL - 5 IS - 4 SP - 1289 EP - 1296 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Zhou, Suqiong A1 - Pan, Yuanwei A1 - Zhang, Jianguang A1 - Li, Yan A1 - Neumann, Falko A1 - Schwerdtle, Tanja A1 - Li, Wenzhong A1 - Haag, Rainer T1 - Dendritic polyglycerol-conjugated gold nanostars with different densities of functional groups to regulate osteogenesis in human mesenchymal stem cells JF - Nanoscale N2 - Nanomaterials play an important role in mimicking the biochemical and biophysical cues of the extracellular matrix in human mesenchymal stem cells (MSCs). Increasing studies have demonstrated the crucial impact of functional groups on MSCs, while limited research is available on how the functional group's density on nanoparticles regulates MSC behavior. Herein, the effects of dendritic polyglycerol (dPG)-conjugated gold nanostars (GNSs) with different densities of functional groups on the osteogenesis of MSCs are systematically investigated. dPG@GNS nanocomposites have good biocompatibility and the uptake by MSCs is in a functional group density-dependent manner. The osteogenic differentiation of MSCs is promoted by all dPG@GNS nanocomposites, in terms of alkaline phosphatase activity, calcium deposition, and expression of osteogenic protein and genes. Interestingly, the dPGOH@GNSs exhibit a slight upregulation in the expression of osteogenic markers, while the different charged densities of sulfate and amino groups show more efficacy in the promotion of osteogenesis. Meanwhile, the sulfated nanostars dPGS20@GNSs show the highest enhancement. Furthermore, various dPG@GNS nanocomposites exerted their effects by regulating the activation of Yes-associated protein (YAP) to affect osteogenic differentiation. These results indicate that dPG@GNS nanocomposites have functional group density-dependent influence on the osteogenesis of MSCs, which may provide a new insight into regulating stem cell fate. Y1 - 2020 U6 - https://doi.org/10.1039/d0nr06570f SN - 2040-3364 SN - 2040-3372 VL - 12 IS - 47 SP - 24006 EP - 24019 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Taylor, Vivien A1 - Goodale, Britton A1 - Raab, Andrea A1 - Schwerdtle, Tanja A1 - Reimer, Ken A1 - Conklin, Sean A1 - Karagas, Margaret R. A1 - Francesconi, Kevin A. T1 - Human exposure to organic arsenic species from seafood JF - The science of the total environment : an international journal for scientific research into the environment and its relationship with man N2 - Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be nontoxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge. KW - Organic arsenic KW - Seafood KW - Arsenosugar KW - Arsenolipid Y1 - 2017 U6 - https://doi.org/10.1016/j.scitotenv.2016.12.113 SN - 0048-9697 SN - 1879-1026 VL - 580 SP - 266 EP - 282 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Ebert, Franziska A1 - Ziemann, Vanessa A1 - Wandt, Viktoria Klara Veronika A1 - Witt, Barbara A1 - Müller, Sandra Marie A1 - Guttenberger, Nikolaus A1 - Bankoglu, Ezgi Eyluel A1 - Stopper, Helga A1 - Raber, Georg A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Cellular toxicological characterization of a thioxolated arsenic-containing hydrocarbon JF - Journal of trace elements in medicine and biology N2 - Arsenolipids, especially arsenic-containing hydrocarbons (AsHC), are an emerging class of seafood originating contaminants. Here we toxicologically characterize a recently identified oxo-AsHC 332 metabolite, thioxo-AsHC 348 in cultured human liver (HepG2) cells. Compared to results of previous studies of the parent compound oxo-AsHC 332, thioxo-AsHC 348 substantially affected cell viability in the same concentration range but exerted about 10-fold lower cellular bioavailability. Similar to oxo-AsHC 332, thioxo-AsHC 348 did not substantially induce oxidative stress nor DNA damage. Moreover, in contrast to oxo-AsHC 332 mitochondria seem not to be a primary subcellular toxicity target for thioxo-AsHC 348. This study indicates that thioxo-AsHC 348 is at least as toxic as its parent compound oxo-AsHC 332 but very likely acts via a different mode of toxic action, which still needs to be identified. Y1 - 2017 U6 - https://doi.org/10.1016/j.jtemb.2020.126563 VL - 61 PB - Elsevier CY - München ER - TY - JOUR A1 - Maares, Maria A1 - Duman, Ayse A1 - Keil, Claudia A1 - Schwerdtle, Tanja A1 - Haase, Hajo T1 - The impact of apical and basolateral albumin on intestinal zinc resorption in the Caco-2/HT-29-MTX co-culture model JF - Metallomics : integrated biometal science N2 - The molecular mechanisms of intestinal zinc resorption and its regulation are still topics of ongoing research. To this end, the application of suitable in vitro intestinal models, optimized with regard to their cellular composition and medium constituents, is of crucial importance. As one vital aspect, the impact of cell culture media or buffer compounds, respectively, on the speciation and cellular availability of zinc has to be considered when investigating zinc resorption. Thus, the present study aims to investigate the impact of serum, and in particular its main constituent serum albumin, on zinc uptake and toxicity in the intestinal cell line Caco-2. Furthermore, the impact of serum albumin on zinc resorption is analyzed using a co-culture of Caco-2 cells and the mucin-producing goblet cell line HT-29-MTX. Apically added albumin significantly impaired zinc uptake into enterocytes and buffered its cytotoxicity. Yet, undigested albumin does not occur in the intestinal lumen in vivo and impairment of zinc uptake was abrogated by digestion of albumin. Interestingly, zinc uptake, as well as gene expression studies of mt1a and selected intestinal zinc transporters after zinc incubation for 24 h, did not show significant differences between 0 and 10% serum. Importantly, the basolateral application of serum in a transport study significantly enhanced fractional apical zinc resorption, suggesting that the occurrence of a zinc acceptor in the plasma considerably affects intestinal zinc resorption. This study demonstrates that the apical and basolateral medium composition is crucial when investigating zinc, particularly its intestinal resorption, using in vitro cell culture. Y1 - 2018 U6 - https://doi.org/10.1039/c8mt00064f SN - 1756-5901 SN - 1756-591X VL - 10 IS - 7 SP - 979 EP - 991 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Duydu, Yalcin A1 - Basaran, Nursen A1 - Ustundag, Aylin A1 - Aydin, Sevtap A1 - Yalcin, Can Ozgur A1 - Anlar, Hatice Gul A1 - Bacanli, Merve A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Schwerdtle, Tanja A1 - Werner, Matthias A1 - Meyer, Sören A1 - Bolt, Hermann M. T1 - Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey JF - Archives of toxicology : official journal of EUROTOX N2 - Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By contrast, studies on boron-mediated developmental effects in females are scarce. The present study was designed to fill this gap. Hundred and ninety nine females residing in Bandirma and Bigadic participated in this study investigating pregnancy outcomes. The participants constituted a study group covering blood boron from low (< 100 ng B/g blood, n = 143) to high (> 150 ng B/g blood, n = 27) concentrations. The mean blood boron concentration and the mean estimated daily boron exposure of the high exposure group was 274.58 (151.81-975.66) ng B/g blood and 24.67 (10.47-57.86) mg B/day, respectively. In spite of the high level of daily boron exposure, boron-mediated adverse effects on induced abortion, spontaneous abortion (miscarriage), stillbirth, infant death, neonatal death, early neonatal death, preterm birth, congenital anomalies, sex ratio and birth weight of newborns were not observed. KW - Boric acid KW - Boron exposure KW - Biological monitoring KW - Developmental toxicity KW - Pregnancy outcomes Y1 - 2018 U6 - https://doi.org/10.1007/s00204-018-2238-4 SN - 0340-5761 SN - 1432-0738 VL - 92 IS - 8 SP - 2475 EP - 2485 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Turrini, Nikolaus G. A1 - Kroepfl, Nina A1 - Jensen, Kenneth Bendix A1 - Reiter, Tamara C. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja A1 - Kroutil, Wolfgang A1 - Kuehnelt, Doris T1 - Biosynthesis and isolation of selenoneine from genetically modified fission yeast JF - Metallomics : integrated biometal science N2 - Selenoneine, a naturally occurring form of selenium, is the selenium analogue of ergothioneine, a sulfur species with health relevance not only as a purported antioxidant but likely also beyond. Selenoneine has been speculated to exhibit similar effects. To study selenoneine's health properties as well as its metabolic transformation, the pure compound is required. Chemical synthesis of selenoneine, however, is challenging and biosynthetic approaches have been sought. We herein report the biosynthesis and isolation of selenoneine from genetically modified fission yeast Schizosaccharomyces pombe grown in a medium containing sodium selenate. After cell lysis and extraction with methanol, selenoneine was purified by three consecutive preparative reversed-phase HPLC steps. The product obtained at the mg level was characterised by high resolution mass spectrometry, NMR and HPLC/ICPMS. Biosynthesis was found to be a promising alternative to chemical synthesis, and should be suitable for upscaling to produce higher amounts of this important selenium species in the future. Y1 - 2018 U6 - https://doi.org/10.1039/c8mt00200b SN - 1756-5901 SN - 1756-591X VL - 10 IS - 10 SP - 1532 EP - 1538 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Kopp, Johannes Florian A1 - Müller, Sandra Marie A1 - Pohl, Gabriele A1 - Lossow, Kristina A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS JF - Journal of trace elements in medicine and biology N2 - 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 mu L) 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 mu L 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, infra- 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 mu g/L serum and 0.05 mu g/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine. Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.04.015 SN - 0946-672X VL - 54 SP - 221 EP - 225 PB - Elsevier CY - München ER - TY - JOUR A1 - Basaran, Nursen A1 - Duydu, Yalcin A1 - Ustundag, Aylin A1 - Taner, Gokce A1 - Aydin, Sevtap A1 - Anlar, Hatice Gul A1 - Yalcin, Can Özgür A1 - Bacanli, Merve A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Schwerdtle, Tanja A1 - Werner, Matthias A1 - Meyer, Sören A1 - Bolt, Hermann M. T1 - Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions JF - Mutation Research/Genetic Toxicology and Environmental Mutagenesis N2 - Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions. KW - Boric acid KW - Boron exposure KW - DNA damage KW - Comet assay Y1 - 2019 U6 - https://doi.org/10.1016/j.mrgentox.2018.12.013 SN - 1383-5718 SN - 1879-3592 VL - 843 SP - 33 EP - 39 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Li, Mingjun A1 - Schlaich, Christoph A1 - Kulka, Michael Willem A1 - Donskyi, Ievgen S. A1 - Schwerdtle, Tanja A1 - Unger, Wolfgang E. S. A1 - Haag, Rainer T1 - Mussel-inspired coatings with tunable wettability, for enhanced antibacterial efficiency and reduced bacterial adhesion JF - Journal of materials chemistry : B, Materials for biology and medicine N2 - Over the last few decades, there has been a tremendous increase in research on antibacterial surface coatings as an alternative strategy against bacterial infections. Although there are several examples of effective strategies to prevent bacterial adhesion, the effect of the wetting properties on the coating was rarely considered as a crucial factor. Here we report an in-depth study on the effect of extreme wettability on the antibacterial efficiency of a silver nanoparticles ( AgNPs)-based coating. By controlling surface polymerization of mussel-inspired dendritic polyglycerol ( MI-dPG) and post-functionalization, surfaces with wetting properties ranging from superhydrophilic to superhydrophobic were fabricated. Subsequently, AgNPs were embedded into the coatings by applying in situ reduction using the free catechols-moieties present in the MI-dPG coating. The resulting polymer coatings exhibited excellent antibacterial ability against planktonic Escherichia coli ( E. coli) DH5a and Staphylococcus aureus ( S. aureus) SH1000. The antibacterial efficiency of the coatings was analyzed by using inductively coupled plasma mass spectrometry ( ICP-MS) and bacterial viability tests. Furthermore, the antifouling properties of the coatings in relation to the antibacterial properties were evaluated. Y1 - 2019 U6 - https://doi.org/10.1039/c9tb00534j SN - 2050-750X SN - 2050-7518 VL - 7 IS - 21 SP - 3438 EP - 3445 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Meyer, Sören A1 - Lopez-Serrano, Aniceto A1 - Mitze, Hanna A1 - Jakubowski, Norbert A1 - Schwerdtle, Tanja T1 - Single-cell analysis by ICP-MS/MS as a fast tool for cellular bioavailability studies of arsenite JF - Metallomics : integrated biometal science N2 - Single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) has become a powerful and fast tool to evaluate the elemental composition at a single-cell level. In this study, the cellular bioavailability of arsenite (incubation of 25 and 50 mu M for 0-48 h) has been successfully assessed by SC-ICP-MS/MS for the first time directly after re-suspending the cells in water. This procedure avoids the normally arising cell membrane permeabilization caused by cell fixation methods (e.g. methanol fixation). The reliability and feasibility of this SC-ICP-MS/MS approach with a limit of detection of 0.35 fg per cell was validated by conventional bulk ICP-MS/MS analysis after cell digestion and parallel measurement of sulfur and phosphorus. Y1 - 2017 U6 - https://doi.org/10.1039/c7mt00285h SN - 1756-5901 SN - 1756-591X VL - 10 IS - 1 SP - 73 EP - 76 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Kröpfl, Nina A1 - Marschall, Talke A. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja A1 - Kuehnelt, Doris T1 - Quantitative determination of the sulfur-containing antioxidant ergothioneine by HPLC/ICP- QQQ-MS JF - Journal of Analytical Atomic Spectrometry N2 - Interest in the sulfur-containing antioxidant ergothioneine calls for reliable analytical methods for its quantification. In this work, a method based on reversed-phase high performance liquid chromatography (RP-HPLC) coupled with elemental mass spectrometry detection in mass shift mode (inductively coupled plasma triple quadrupole mass spectrometry, ICP-QQQ-MS) using oxygen as the reaction gas was developed for the element-selective determination of ergothioneine in complex biological matrices. Application of an instrumental setup using a 6-port-valve and the introduction of a methanol gradient allowed the time-efficient analysis of samples containing strongly retained sulfur species besides ergothioneine without compromising ICPMS detection. In aqueous solution, limits of detection and quantification (LOD and LOQ) of the optimized method for m/z 32 -> 48 (SO+) were 0.23 mu g S per L and 0.80 mu g S per L, respectively; measurements in a complex matrix (human hepatocyte carcinoma cells, HepG2) resulted in an LOD of 0.6 mu g S per L and an LOQ of 2.3 mu g S per L. Recoveries of ergothioneine from cell pellets spiked with the analyte before cell lysis (97 +/- 3%) matched those obtained for cell culture medium spiked before syringe filtration (96 +/- 9%) demonstrating that sample preparation did not impair the quantitative determination of ergothioneine. When HepG2 cells were exposed to ergothioneine via the culture medium, they showed low absorption; approximately 3% of the added ergothioneine was found in cell lysates, while most of it (>= 85%) remained in the cell culture medium. The method is capable of separating ergothioneine from other biologically relevant sulfur-containing species and is expected to be of broad future use. Furthermore, the potential use for the simultaneous separation of selenium species, thereby extending the scope of possible applications, was demonstrated by applying it to water extracts of oyster mushrooms. Y1 - 2017 U6 - https://doi.org/10.1039/c7ja00030h SN - 0267-9477 SN - 1364-5544 VL - 32 SP - 1571 EP - 1581 PB - Royal Society of Chemistry CY - Cambridge ER -