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 - GEN 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 T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1086 KW - zinc KW - free zinc KW - serum KW - biomarker KW - fluorescent probe KW - Zinypr-1 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-472833 SN - 1866-8372 IS - 1086 ER - TY - JOUR A1 - Aschner, Michael A. A1 - Palinski, Catherine A1 - Sperling, Michael A1 - Karst, U. A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Imaging metals in Caenorhabditis elegans JF - Metallomics : integrated biometal science N2 - Systemic trafficking and storage of essential metal ions play fundamental roles in living organisms by serving as essential cofactors in various cellular processes. Thereby metal quantification and localization are critical steps in understanding metal homeostasis, and how their dyshomeostasis might contribute to disease etiology and the ensuing pathologies. Furthermore, the amount and distribution of metals in organisms can provide insight into their underlying mechanisms of toxicity and toxicokinetics. While in vivo studies on metal imaging in mammalian experimental animals are complex, time- and resource-consuming, the nematode Caenorhabditis elegans (C. elegans) provides a suitable comparative and complementary model system. Expressing homologous genes to those inherent to mammals, including those that regulate metal homeostasis and transport, C. elegans has become a powerful tool to study metal homeostasis and toxicity. A number of recent technical advances have been made in the development and application of analytical methods to visualize metal ions in C. elegans. Here, we briefly summarize key findings and challenges of the three main techniques and their application to the nematode, namely sensing fluorophores, microbeam synchrotron radiation X-ray fluorescence as well as laser ablation ( LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS). Y1 - 2017 U6 - https://doi.org/10.1039/c6mt00265j SN - 1756-5901 SN - 1756-591X VL - 9 SP - 357 EP - 364 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Baesler, Jessica A1 - Kopp, Johannes F. A1 - Pohl, Gabriele A1 - Aschner, Michael A1 - Haase, Hajo A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Zn homeostasis in genetic models of Parkinson’s disease in Caenorhabditis elegans JF - Journal of trace elements in medicine and biology KW - Caenorhabditis elegans KW - Zinc KW - Zinc homeostasis KW - Parkinson disease KW - Labile zinc Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.05.005 SN - 0946-672X VL - 55 SP - 44 EP - 49 PB - Elsevier GMBH CY - München ER - TY - JOUR A1 - Baesler, Jessica A1 - Kopp, Johannes Florian A1 - Pohl, Gabriele A1 - Aschner, Michael A1 - Haase, Hajo A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Zn homeostasis in genetic models of Parkinson’s disease in Caenorhabditis elegans JF - Journal of Trace Elements in Medicine and Biology N2 - While the underlying mechanisms of Parkinson’s disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD. KW - Caenorhabditis elegans KW - Zinc KW - Zinc homeostasis KW - Parkinson disease KW - Labile zinc Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.05.005 VL - 55 SP - 44 EP - 49 PB - Elsevier CY - München ER - TY - GEN A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1364 KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-514995 SN - 1866-8372 IS - 8 ER - TY - JOUR A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis JF - Molecular Nutrition and Food Research N2 - 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. KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - https://doi.org/10.1002/mnfr.202001176 SN - 1613-4133 SN - 1613-4125 VL - 65 IS - 8 SP - 1 EP - 11 PB - Wiley-VCH GmbH CY - Weinheim 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 - Başaran, Nurşen A1 - Duydu, Yalçın A1 - Üstündağ, Aylin A1 - Taner, Gökçe A1 - Aydin Dilsiz, Sevtap A1 - Anlar, Hatice Gül A1 - Yalçin, Can Özgür A1 - Bacanli, Merve A1 - Golka, Klaus A1 - Schwerdtle, Tanja A1 - Bolt, Hermann M. T1 - Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females DNA damage in lymphocytes and buccal cells of boron exposed females JF - Journal of trace elements in medicine and biology N2 - Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boronpoor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). 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 Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.03.004 SN - 0946-672X VL - 53 SP - 150 EP - 153 PB - Elsevier B.V. CY - München ER - TY - JOUR A1 - Bornhorst, Julia A1 - Ebert, Franziska A1 - Meyer, Sören A1 - Ziemann, Vanessa A1 - Xiong, Chan A1 - Guttenberger, Nikolaus A1 - Raab, Andrea A1 - Baesler, Jessica A1 - Aschner, Michael A1 - Feldmann, Jörg A1 - Francesconi, Kevin A1 - Raber, Georg A1 - Schwerdtle, Tanja T1 - Toxicity of three types of arsenolipids BT - species-specific effects in Caenorhabditis elegans JF - Metallomics N2 - Although fish and seafood are well known for their nutritional benefits, they contain contaminants that might affect human health. Organic lipid-soluble arsenic species, so called arsenolipids, belong to the emerging contaminants in these food items; their toxicity has yet to be systematically studied. Here, we apply the in vivo model Caenorhabditis elegans to assess the effects of two arsenic-containing hydrocarbons (AsHC), a saturated arsenic-containing fatty acid (AsFA), and an arsenic-containing triacylglyceride (AsTAG) in a whole organism. Although all arsenolipids were highly bioavailable in Caenorhabditis elegans, only the AsHCs were substantially metabolized to thioxylated or shortened metabolic products and induced significant toxicity, affecting both survival and development. Furthermore, the AsHCs were several fold more potent as compared to the toxic reference arsenite. This study clearly indicates the need for a full hazard identification of subclasses of arsenolipids to assess whether they pose a risk to human health. Y1 - 2020 U6 - https://doi.org/https://doi.org/10.1039/d0mt00039f SN - 1756-591X SN - 1756-5901 VL - 12 IS - 5 SP - 794 EP - 798 PB - Oxford University Press CY - Cambridge ER - TY - JOUR A1 - Bornhorst, Julia A1 - Kipp, Anna P. A1 - Haase, Hajo A1 - Meyer, Soeren A1 - Schwerdtle, Tanja T1 - The crux of inept biomarkers for risks and benefits of trace elements JF - Trends in Analytical Chemistry N2 - Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE. KW - Trace elements KW - Copper KW - Zinc KW - Manganese KW - Selenium KW - Biomarker KW - Inductively coupled plasma mass spectrometry KW - Hyphenated techniques KW - Isotope ratios Y1 - 2018 U6 - https://doi.org/10.1016/j.trac.2017.11.007 SN - 0165-9936 SN - 1879-3142 VL - 104 SP - 183 EP - 190 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Bzymek, Robert A1 - Horsthemke, Markus A1 - Isfort, Katrin A1 - Mohr, Simon A1 - Tjaden, Kerstin A1 - Mueller-Tidow, Carsten A1 - Thomann, Marlies A1 - Schwerdtle, Tanja A1 - Baehler, Martin A1 - Schwab, Albrecht A1 - Hanley, Peter J. T1 - Real-time two- and three-dimensional imaging of monocyte motility and navigation on planar surfaces and in collagen matrices: roles of Rho JF - Scientific reports N2 - We recently found that macrophages from RhoA/RhoB double knockout mice had increased motility of the cell body, but severely impaired retraction of the tail and membrane extensions, whereas RhoA-or RhoB-deficient cells exhibited mild phenotypes. Here we extended this work and investigated the roles of Rho signaling in primary human blood monocytes migrating in chemotactic gradients and in various settings. Monocyte velocity, but not chemotactic navigation, was modestly dependent on Rho-ROCK-myosin II signaling on a 2D substrate or in a loose collagen type I matrix. Viewed by time-lapse epi-fluorescence microscopy, monocytes appeared to flutter rather than crawl, such that the 3D surface topology of individual cells was difficult to predict. Spinning disk confocal microscopy and 3D reconstruction revealed that cells move on planar surfaces and in a loose collagen matrix using prominent, curved planar protrusions, which are rapidly remodeled and reoriented, as well as resorbed. In a dense collagen type I matrix, there is insufficient space for this mode and cells adopt a highly Rho-dependent, lobular mode of motility. Thus, in addition to its role in tail retraction on 2D surfaces, Rho is critical for movement in confined spaces, but is largely redundant for motility and chemotaxis in loose matrices. Y1 - 2016 U6 - https://doi.org/10.1038/srep25016 SN - 2045-2322 VL - 6 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Chakraborty, Sudipta A1 - Chen, Pan A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Bowman, Aaron B. A1 - Aschner, Michael A. T1 - Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C. elegans N2 - Overexposure to the essential metal manganese (Mn) can result in an irreversible condition known as manganism that shares similar pathophysiology with Parkinson's disease (PD), including dopaminergic (DAergic) cell loss that leads to motor and cognitive impairments. However, the mechanisms behind this neurotoxicity and its relationship with PD remain unclear. Many genes confer risk for autosomal recessive, early-onset PD, including the parkin/PARK2 gene that encodes for the E3 ubiquitin ligase Parkin. Using Caenorhabditis elegans (C. elegans) as an invertebrate model that conserves the DAergic system, we previously reported significantly increased Mn accumulation in pdr-1/parkin mutants compared to wildtype (WT) animals. For the current study, we hypothesize that this enhanced accumulation is due to alterations in Mn transport in the pdr-1 mutants. While no change in mRNA expression of the major Mn importer proteins (smf-1-3) was found in pdr-1 mutants, significant downregulation in mRNA levels of the putative Mn exporter ferroportin (fpn-1.1) was observed. Using a strain overexpressing fpn-1.1 in worms lacking pdr-1, we show evidence for attenuation of several endpoints of Mn-induced toxicity, including survival, metal accumulation, mitochondrial copy number and DAergic integrity, compared to pdr-1 mutants alone. These changes suggest a novel role of pdr-1 in modulating Mn export through altered transporter expression, and provides further support of metal dyshomeostasis as a component of Parkinsonism pathophysiology. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 290 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-99508 ER - TY - JOUR A1 - Chakraborty, Sudipta A1 - Chen, Pan A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Bowman, Aaron B. A1 - Aschner, Michael A. T1 - Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C-elegans JF - Metallomics : integrated biometal science Y1 - 2015 U6 - https://doi.org/10.1039/c5mt00052a SN - 1756-5901 SN - 1756-591X VL - 7 IS - 5 SP - 847 EP - 856 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Cramer, Sandra A1 - Tacke, Sebastian A1 - Bornhorst, Julia A1 - Klingauf, Jürgen A1 - Schwerdtle, Tanja A1 - Galla, Hans-Joachim T1 - The Influence of Silver Nanoparticles on the Blood-Brain and the Blood-Cerebrospinal Fluid Barrier in vitro JF - Journal of Nanomedicine & Nanotechnology N2 - The use of silver nanoparticles in medical and consumer products such as wound dressings, clothing and cosmetic has increased significantly in recent years. Still, the influence of these particles on our health and especially on our brain, has not been examined adequately up to now. We studied the influence of AgEO- (Ethylene Oxide) and AgCitrate-Nanoparticles (NPs) on the protective barriers of the brain, namely the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (blood-CSF) barrier in vitro. The NPs toxicity was evaluated by examining changes in membrane integrity, cell morphology, barrier properties, oxidative stress and inflammatory reactions. AgNPs decreased cell viability, disturbed barrier integrity and tight junctions and triggered oxidative stress and DNA strand breaks. However, all mentioned effects were, at least partly, suppressed by a Citrate-coating and were most pronounced in the cells of the BBB as compared to the epithelial cells representing the blood-CSF barrier. AgEO- but not AgCitrate-NPs also triggered an inflammatory reaction in porcine brain capillary endothelial cells (PBCEC), which represent the BBB. Our data indicate that AgNPs may cause adverse effects within the barriers of the brain, but their toxicity can be reduced by choosing an appropriate coating material. Y1 - 2014 U6 - https://doi.org/10.4172/2157-7439.1000225 SN - 2157-7439 VL - 5 IS - 5 ER - TY - JOUR A1 - Crone, Barbara A1 - Aschner, Michael A. A1 - Schwerdtle, Tanja A1 - Karst, Uwe A1 - Bornhorst, Julia T1 - Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS JF - Metallomics N2 - cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable. Y1 - 2015 U6 - https://doi.org/10.1039/c5mt00096c SN - 1756-591X SN - 1756-5901 VL - 2015 IS - 7 SP - 1189 EP - 1195 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Crone, Barbara A1 - Aschner, Michael A. A1 - Schwerdtle, Tanja A1 - Karst, Uwe A1 - Bornhorst, Julia T1 - Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS N2 - cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 192 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-80031 SP - 1189 EP - 1195 ER - TY - JOUR A1 - Crone, Barbara A1 - Aschner, Michael A. A1 - Schwerdtle, Tanja A1 - Karst, Uwe A1 - Bornhorst, Julia T1 - Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS JF - Metallomics : integrated biometal science N2 - cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 mm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose) metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable. Y1 - 2015 U6 - https://doi.org/10.1039/c5mt00096c SN - 1756-5901 SN - 1756-591X VL - 7 IS - 7 SP - 1189 EP - 1195 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Draude, F. A1 - Pelster, A. A1 - Koersgen, M. A1 - Kassenboehmer, R. A1 - Schwerdtle, Tanja A1 - Muething, J. A1 - Arlinghaus, H. F. T1 - ToF-SIMS imaging of plasma membrane lipids with sub-micrometer resolution JF - Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films N2 - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for label-free analyses of the molecular lateral distribution of two different epithelial cell membranes (PANC-1 and UROtsa). The goal of the research was to enhance the ion yield of specific membrane molecules for improving the membrane imaging capability of ToF-SIMS on the nanoscale lateral dimension. For this task, a special silicon wafer sandwich preparation technique was optimized using different wafer materials, spacers, and washing procedures. Under optimized preparation conditions, the yield could be significantly enhanced, allowing imaging of the inhomogeneous distribution of phosphocholine (common head group for phosphatidylcholine and sphingomyelin) of a PANC-1 cell membrane's outer lipid layer with a lateral resolution of less than 200nm. Copyright (c) 2014 John Wiley & Sons, Ltd. KW - ToF-SIMS KW - high-resolution imaging KW - membrane analysis KW - lipid analysis KW - yield enhancement KW - sample preparation Y1 - 2014 U6 - https://doi.org/10.1002/sia.5576 SN - 0142-2421 SN - 1096-9918 VL - 46 SP - 127 EP - 130 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Draude, Felix A1 - Körsgen, Martin A1 - Pelster, Andreas A1 - Schwerdtle, Tanja A1 - Müthing, Johannes A1 - Arlinghaus, Heinrich F. T1 - Characterization of freeze-fractured epithelial plasma membranes on nanometer scale with ToF-SIMS JF - Analytical & bioanalytical chemistry N2 - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to characterize the freeze-fracturing process of human epithelial PANC-1 and UROtsa cells. For this purpose, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine standard samples were investigated to find specific signals with both high specificity and signal intensity. The results were used to investigate single cells of subconfluent cell layers prepared with a special silicon wafer sandwich preparation technique. This freeze-fracturing technique strips cell membranes off the cells, isolating them on opposing silicon wafer substrates. Criteria were found for defining regions with stripped off cell membranes and, on the opposing wafer, complementary regions with the remaining cells. Measured ethanolamine/choline and serine/choline ratios in these regions clearly showed that in the freeze-fracturing process, the lipid bilayer of the plasma membrane is split along its central zone. Accordingly, only the outer lipid monolayer is stripped off the cell, while the inner lipid monolayer remains attached to the cell on the opposing wafer, thus allowing detailed analysis of a single lipid monolayer. Furthermore, it could be shown that using different washing procedures did not influence the transmembrane lipid distribution. Under optimized preparation conditions, it became feasible to detect lipids with a lateral resolution of approximately 100 nm. The data indicate that ToF-SIMS would be a very useful technique to study with very high lateral resolution changes in lipid composition caused, for example, by lipid storage diseases or pharmaceuticals that interfere with the lipid metabolism. KW - ToF-SIMS imaging KW - Life science KW - Lipid KW - Freeze-fracturing KW - Membrane KW - Transmembrane asymmetry Y1 - 2015 U6 - https://doi.org/10.1007/s00216-014-8334-2 SN - 1618-2642 SN - 1618-2650 VL - 407 IS - 8 SP - 2203 EP - 2211 PB - Springer CY - Heidelberg ER - TY - GEN A1 - Duydu, Yalcin A1 - Basaran, Nursen A1 - Aydin, Sevtap A1 - Ustundag, Aylin A1 - Goktas, Hatica Gul A1 - Yalcin, Can Özgür A1 - Bacanli, Merve A1 - Sarigol, Zehra A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Schwerdtle, Tanja A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Bolt, Hermann M. T1 - Investigation of boron mediated reproductive and developmental effects in highly boron exposed population T2 - Toxicology letters Y1 - 2017 U6 - https://doi.org/10.1016/j.toxlet.2017.07.259 SN - 0378-4274 SN - 1879-3169 VL - 280 SP - S94 EP - S94 PB - Elsevier CY - Clare 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 - 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 - Duydu, Yalcin A1 - Basaran, Nursen A1 - Yalcin, Can Özgür A1 - Ustundag, Aylin A1 - Aydin, Sevtap 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 - Bolt, Hermann M. T1 - Boron-exposed male workers in Turkey BT - no change in sperm Y:X chromosome ratio and in offspring's sex ratio JF - Archives of toxicology : official journal of EUROTOX N2 - Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. In the present study, 304 male workers in Bandirma and Bigadic (Turkey) with different degrees of occupational and environmental exposure to boron were investigated. Boron was quantified in blood, urine and semen, and the persons were allocated to exposure groups along B blood levels. In the highest ("extreme") exposure group (n = 69), calculated mean daily boron exposures, semen boron and blood boron concentrations were 44.91 +/- 18.32 mg B/day, 1643.23 +/- 965.44 ng B/g semen and 553.83 +/- 149.52 ng B/g blood, respectively. Overall, an association between boron exposure and Y:X sperm ratios in semen was not statistically significant (p > 0.05). Also, the mean Y:X sperm ratios in semen samples of workers allocated to the different exposure groups were statistically not different in pairwise comparisons (p > 0.05). Additionally, a boron-associated shift in sex ratio at birth towards female offspring was not visible. In essence, the present results do not support an association between boron exposure and decreased Y:X sperm ratio in males, even under extreme boron exposure conditions. KW - Paternal exposure KW - Boron exposure KW - Y:X chromosome ratio KW - Sex ratio at birth Y1 - 2019 U6 - https://doi.org/10.1007/s00204-019-02391-z SN - 0340-5761 SN - 1432-0738 VL - 93 IS - 3 SP - 743 EP - 751 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Dünkelberg, Sophie A1 - Maywald, Martina A1 - Schmitt, Anne Kristina A1 - Schwerdtle, Tanja A1 - Meyer, Sören A1 - Rink, Lothar T1 - The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells JF - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology N2 - Scope: Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium. Methods and Results: Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium. Conclusion: This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways. KW - Foxp3 KW - regulatory T cells KW - sodium KW - T helper 17 cells KW - zinc Y1 - 2020 U6 - https://doi.org/10.1002/mnfr.201900245 SN - 1613-4133 VL - 64 IS - 2 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Ebert, Franziska A1 - Meyer, Sören A1 - Leffers, Larissa A1 - Raber, Georg A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Toxicological characterisation of a thio-arsenosugar-glycerol in human cells JF - Journal of trace elements in medicine and biology N2 - Arsenosugars are water-soluble arsenic species predominant in marine algae and other seafood including mussels and oysters. They typically occur at levels ranging from 2 to 50 mg arsenic/kg dry weight. Most of the arsenosugars contain arsenic as a dimethylarsinoyl group (Me2As(O)-), commonly referred to as the oxo forms, but thio analogues have also been identified in marine organisms and as metabolic products of oxo-arsenosugars. So far, no data regarding toxicity and toxicokinetics of thio-arsenosugars are available. This in vitro-based study indicates that thio-dimethylarsenosugar-glycerol exerts neither pronounced cytotoxicity nor genotoxicity even though this arsenical was bioavailable to human hepatic (HepG2) and urothelial (UROtsa) cells. Experiments with the Caco-2 intestinal barrier model mimicking human absorption indicate for the thio-arsenosugar-glycerol higher intestinal bioavailability as compared to the oxo-arsenosugars. Nevertheless, absorption estimates were much lower in comparison to other arsenicals including arsenite and arsenic-containing hydrocarbons. Arsenic speciation in cell lysates revealed that HepG2 cells are able to metabolise the thio-arsenosugar-glycerol to some extent to dimethylarsinic acid (DMA). These first in vitro data cannot fully exclude risks to human health related to the presence of thio-arsenosugars in food. (C) 2016 Elsevier GmbH. All rights reserved. KW - Arsenic KW - Thio-arsenosugar-glycerol KW - Toxicity KW - Toxicokinetics KW - Genotoxicity KW - Metabolism Y1 - 2016 U6 - https://doi.org/10.1016/j.jtemb.2016.04.013 SN - 0946-672X VL - 38 SP - 150 EP - 156 PB - Springer Publishing Company CY - Jena ER - TY - JOUR A1 - Ebert, Franziska A1 - Thomann, Marlies A1 - Witt, Barbara A1 - Müller, Sandra Marie A1 - Meyer, Sören A1 - Weber, Till A1 - Christmann, Markus A1 - Schwerdtle, Tanja T1 - Evaluating long-term cellular effects of the arsenic species thio-DMA(V): qPCR-based gene expression as screening tool JF - Journal of trace elements in medicine and biology N2 - Thio-dimethylarsinic acid (thio-DMA(V)) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMA(V) exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21 days) in vitro incubation of thio-DMA(V) on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMAv incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMA(V) causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1,Lig1, XRCC1,DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMA(V) after long-term incubation. (C) 2016 Elsevier GmbH. All rights reserved. KW - Thio-dimethylarsinic acid KW - Long-term cellular toxicity KW - qPCR-based gene expression screening KW - GADD45A and GADD45G KW - DNMT1 KW - Cellular damage response Y1 - 2016 U6 - https://doi.org/10.1016/j.jtemb.2016.06.004 SN - 0946-672X VL - 37 SP - 78 EP - 84 PB - Yokohama Publishers CY - Jena 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 - Finke, Hannah A1 - Wandt, Viktoria Klara Veronika A1 - Ebert, Franziska A1 - Guttenberger, Nikolaus A1 - Glabonjat, Ronald A. A1 - Stiboller, Michael A1 - Francesconi, Kevin A. A1 - Raber, Georg A1 - Schwerdtle, Tanja T1 - Toxicological assessment of arsenic-containing phosphatidylcholines in HepG2 cells N2 - Arsenolipids include a wide range of organic arsenic species that occur naturally in seafood and thereby contribute to human arsenic exposure. Recently arsenic-containing phosphatidylcholines (AsPCs) were identified in caviar, fish, and algae. In this first toxicological assessment of AsPCs, we investigated the stability of both the oxo- and thioxo-form of an AsPC under experimental conditions, and analyzed cell viability, indicators of genotoxicity and biotransformation in human liver cancer cells (HepG2). Precise toxicity data could not be obtained owing to the low solubility in the cell culture medium of the thioxo-form, and the ease of hydrolysis of the oxo-form, and to a lesser degree the thioxo-form. Hydrolysis resulted amongst others in the respective constituent arsenic-containing fatty acid (AsFA). Incubation of the cells with oxo-AsPC resulted in a toxicity similar to that determined for the hydrolysis product oxo-AsFA alone, and there were no indices for genotoxicity. Furthermore, the oxo-AsPC was readily taken up by the cells resulting in high cellular arsenic concentrations (50 μM incubation: 1112 ± 146 μM As cellular), whereas the thioxo-AsPC was substantially less bioavailable (50 μM incubation: 293 ± 115 μM As cellular). Speciation analysis revealed biotransformation of the AsPCs to a series of AsFAs in the culture medium, and, in the case of the oxo-AsPC, to as yet unidentified arsenic species in cell pellets. The results reveal the difficulty of toxicity studies of AsPCs in vitro, indicate that their toxicity might be largely governed by their arsenic fatty acid content and suggest a multifaceted human metabolism of food derived complex arsenolipids. KW - Biochemistry KW - Biological Sciences KW - Science and Mathematics KW - Books KW - Journals Y1 - 2020 U6 - https://doi.org/10.1039/d0mt00073f VL - 12 IS - 7 SP - 1159 EP - 1170 PB - Oxford University CY - Cambridge ER - TY - JOUR A1 - Finke, Hannah A1 - Winkelbeiner, Nicola Lisa A1 - Lossow, Kristina A1 - Hertel, Barbara A1 - Wandt, Viktoria Klara Veronika A1 - Schwarz, Maria A1 - Pohl, Gabriele A1 - Kopp, Johannes Florian A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice BT - trace element status, genomic stability, inflammation, and epigenetics JF - Molecular nutrition & food research N2 - Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied. Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass‐spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron‐related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation. Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects. Y1 - 2020 U6 - https://doi.org/10.1002/mnfr.202000325 SN - 1613-4125 VL - 64 IS - 16 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Frede, Katja A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja A1 - Baldermann, Susanne T1 - Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells JF - Journal of agricultural and food chemistry : a publication of the American Chemical Society N2 - The degeneration of the retinal pigment epithelium caused by oxidative damage is a stage of development in age related macular degeneration (AMD). The carotenoid lutein is a major macular pigment that may reduce the incidence and progression of AMD, but the underlying mechanism is currently not fully understood. Carotenoids are known to be direct antioxidants. However, carotenoids can also activate cellular pathways resulting in indirect antioxidant effects. Here, we investigate the influence of lutein on the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes in human retinal pigment epithelial cells (ARPE-19 cells) using lutein-loaded Tween40 micelles. The micelles were identified as a suitable delivery system since they were nontoxic in APRE-19 cells up to 0.04% Tween40 and led to a cellular lutein accumulation of 62 mu M +/- 14 mu M after 24 h. Lutein significantly enhanced Nrf2 translocation to the nucleus 1.5 +/- 0.4-fold compared to that of unloaded micelles after 4 h. Furthermore, lutein treatment for 24 h significantly increased the transcripts of NAD(P)H:quinone oxidoreductase 1 (NQO1) by 1.7 +/- 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 +/- 0.1-fold, and heme oxygenase-1 (HO-1) by 1.8 +/- 0.3-fold. Moreover, we observed a significant enhancement of NQO1 activity by 1.2 +/- 0.1-fold. Collectively, this study indicates that lutein not only serves as a direct antioxidant but also activates Nrf 2 in ARPE-19 cells. KW - lutein KW - Nif2 KW - ARPE-19 cells KW - AMD KW - Tween40 micelles Y1 - 2017 U6 - https://doi.org/10.1021/acs.jafc.7b01929 SN - 0021-8561 SN - 1520-5118 VL - 65 SP - 5944 EP - 5952 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Hackethal, Christin A1 - Kopp, Johannes Florian A1 - Sarvan, Irmela A1 - Schwerdtle, Tanja A1 - Lindtner, Oliver T1 - Total arsenic and water-soluble arsenic species in foods of the first German total diet study (BfR MEAL Study) JF - Food chemistry N2 - Arsenic can occur in foods as inorganic and organic forms. Inorganic arsenic is more toxic than most watersoluble organic arsenic compounds such as arsenobetaine, which is presumed to be harmless for humans. Within the first German total diet study, total arsenic, inorganic arsenic, arsenobetaine, dimethylarsinic acid and monomethylarsonic acid were analyzed in various foods. Highest levels of total arsenic were found in fish, fish products and seafood (mean: 1.43 mg kg(-1); n = 39; min-max: 0.01-6.15 mg kg(-1)), with arsenobetaine confirmed as the predominant arsenic species (1.233 mg kg 1; n = 39; min-max: 0.01-6.23 mg kg (1)). In contrast, inorganic arsenic was determined as prevalent arsenic species in terrestrial foods (0.02 mg kg (1); n = 38; min-max: 0-0.11 mg kg (1)). However, the toxicity of arsenic species varies and measurements are necessary to gain information about the composition and changes of arsenic species in foods due to household processing of foods. KW - Occurrence data KW - Food KW - Total arsenic KW - Arsenic speciation KW - Inductively KW - coupled plasma mass spectrometry Y1 - 2021 U6 - https://doi.org/10.1016/j.foodchem.2020.128913 SN - 0308-8146 SN - 1873-7072 VL - 346 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Henze, Andrea A1 - Homann, Thomas A1 - Rohn, Isabelle A1 - Aschner, Michael A. A1 - Link, Christopher D. A1 - Kleuser, Burkhard A1 - Schweigert, Florian J. A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin JF - Scientific reports N2 - The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling. KW - n-acetyl-cysteine KW - s-glutathionylation KW - force-field KW - c. elegans KW - life-span KW - protein KW - cells KW - menadione KW - disease KW - binding Y1 - 2016 U6 - https://doi.org/10.1038/srep37346 SN - 2045-2322 VL - 6 PB - Nature Publishing Group CY - London ER - TY - GEN A1 - Henze, Andrea A1 - Homann, Thomas A1 - Rohn, Isabelle A1 - Aschner, Michael A. A1 - Link, Christopher D. A1 - Kleuser, Burkhard A1 - Schweigert, Florian J. A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin N2 - The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 312 KW - binding KW - c. elegans KW - cells KW - disease KW - force-field KW - life-span KW - menadione KW - n-acetyl-cysteine KW - protein KW - s-glutathionylation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-103674 ER - TY - JOUR A1 - Henze, Andrea A1 - Homann, Thomas A1 - Rohn, Isabelle A1 - Aschner, Michael A. A1 - Link, Christopher D. A1 - Kleuser, Burkhard A1 - Schweigert, Florian J. A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin JF - Scientific reports N2 - The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time-and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling. Y1 - 2016 U6 - https://doi.org/10.1038/srep37346 SN - 2045-2322 VL - 6 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Jacques, Mauricio Tavares A1 - Bornhorst, Julia A1 - Soares, Marcell Valandro A1 - Schwerdtle, Tanja A1 - Garcia, Solange A1 - Avila, Daiana Silva T1 - Reprotoxicity of glyphosate-based formulation in Caenorhabditis elegans is not due to the active ingredient only JF - Environmental pollution N2 - Pesticides guarantee us high productivity in agriculture, but the long-term costs have proved too high. Acute and chronic intoxication of humans and animals, contamination of soil, water and food are the consequences of the current demand and sales of these products. In addition, pesticides such as glyphosate are sold in commercial formulations which have inert ingredients, substances with unknown composition and proportion. Facing this scenario, toxicological studies that investigate the interaction between the active principle and the inert ingredients are necessary. The following work proposed comparative toxicology studies between glyphosate and its commercial formulation using the alternative model Caenorhabditis elegans. Worms were exposed to different concentrations of the active ingredient (glyphosate in monoisopropylamine salt) and its commercial formulation. Reproductive capacity was evaluated through brood size, morphological analysis of oocytes and through the MD701 strain (bcIs39), which allows the visualization of germ cells in apoptosis. In addition, the metal composition in the commercial formulation was analyzed by ICP-MS. Only the commercial formulation of glyphosate showed significant negative effects on brood size, body length, oocyte size, and the number of apoptotic cells. Metal analysis showed the presence of Hg, Fe, Mn, Cu, Zn, As, Cd and Pb in the commercial formulation, which did not cause reprotoxicity at the concentrations found. However, metals can bio-accumulate in soil and water and cause environmental impacts. Finally, we demonstrated that the addition of inert ingredients increased the toxic profile of the active ingredient glyphosate in C. elegans, which reinforces the need of components description in the product labels. (C) 2019 Elsevier Ltd. All rights reserved. KW - Glyphosate KW - Inert ingredients KW - Reproduction KW - Oocytes KW - Development KW - Metals Y1 - 2019 U6 - https://doi.org/10.1016/j.envpol.2019.06.099 SN - 0269-7491 SN - 1873-6424 VL - 252 SP - 1854 EP - 1862 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Knoche, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - LC-HRMS-Based identification of transformation products of the drug salinomycin generated by electrochemistry and liver microsome JF - Antibiotics N2 - The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction. KW - salinomycin KW - ionophore antibiotics KW - transformation product KW - electrochemistry KW - rat KW - human liver microsomes KW - HRMS Y1 - 2022 U6 - https://doi.org/10.3390/antibiotics11020155 SN - 2079-6382 VL - 11 IS - 2 PB - MDPI CY - Basel 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 - GEN A1 - Kotthoff, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid+ chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1340 KW - transformation products KW - monensin KW - veterinary drugs KW - electrochemistry KW - hydrolysis KW - LC/HRMS Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473262 SN - 1866-8372 IS - 1340 ER - TY - JOUR A1 - Kotthoff, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis JF - Molecules N2 - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation. KW - transformation products KW - monensin KW - veterinary drugs KW - electrochemistry KW - hydrolysis KW - LC/HRMS Y1 - 2019 U6 - https://doi.org/10.3390/molecules24152732 SN - 1420-3049 VL - 24 IS - 15 PB - MDPI CY - Basel ER - TY - JOUR A1 - Kotthoff, Lisa A1 - O'Callaghan, Sarah-Louise A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry JF - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown. KW - veterinary drug KW - moxidectin KW - transformation products KW - electrochemistry KW - photochemistry KW - LC KW - HRMS Y1 - 2020 U6 - https://doi.org/10.1007/s00216-020-02572-1 SN - 1618-2642 SN - 1618-2650 VL - 412 IS - 13 SP - 3141 EP - 3152 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Kroepfl, Nina A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja A1 - Kuehnelt, Doris T1 - Selenoneine and ergothioneine in human blood cells determined simultaneously by HPLC/ICP-QQQ-MS JF - Journal of Analytical Atomic Spectrometry N2 - The possible relevance to human health of selenoneine and its sulfur-analogue ergothioneine has generated interest in their quantitative determination in biological samples. To gain more insight into the similarities and differences of these two species, a method for their simultaneous quantitative determination in human blood cells using reversed-phase high performance liquid chromatography (RP-HPLC) coupled to inductively coupled plasma triple quadrupole mass spectrometry (ICP-QQQ-MS) is presented. Spectral interferences hampering the determination of sulfur and selenium by ICPMS are overcome by introducing oxygen to the reaction cell. To access selenoneine and ergothioneine in the complex blood matrix, lysis of the cells with cold water followed by cut-off filtration (3000 Da) is performed. Recoveries based on blood cells spiked with selenoneine and ergothioneine were between 80% and 85%. The standard deviation of the method was around 0.10 mg S per L for ergothioneine (corresponding to relative standard deviations (RSD) between 10-1% for ergothioneine concentrations of 1-10 mg S per L) and 0.25 g Se per L for selenoneine (RSDs of 25-2% for concentrations of 1-10 g Se per L). The method was applied to blood cell samples from three volunteers which showed selenoneine and ergothioneine concentrations in the range of 3.25 to 7.35 g Se per L and 0.86 to 6.44 mg S per L, respectively. The method is expected to be of wide use in future studies investigating the dietary uptake of selenoneine and ergothioneine and their relevance in human health. Y1 - 2018 U6 - https://doi.org/10.1039/c8ja00276b SN - 0267-9477 SN - 1364-5544 VL - 34 IS - 1 SP - 127 EP - 134 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 - TY - JOUR A1 - Kuhn, Eugênia Carla A1 - Tavares Jacques, Maurício A1 - Teixeira, Daniela A1 - Meyer, Sören A1 - Gralha, Thiago A1 - Roehrs, Rafael A1 - Camargo, Sandro A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia A1 - Ávila, Daiana Silva T1 - Ecotoxicological assessment of Uruguay River and affluents pre- and biomonitoring JF - Environmental science and pollution research : ESPR N2 - Uruguay River is the most important river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety. KW - Heavy metals KW - Pesticides KW - Contamination KW - Arsenic KW - Environmental KW - pollution KW - Uruguay River Y1 - 2021 U6 - https://doi.org/10.1007/s11356-020-11986-4 SN - 0944-1344 SN - 1614-7499 VL - 28 IS - 17 SP - 21730 EP - 21741 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Kumar, Kevin K. A1 - Goodwin, Cody R. A1 - Uhouse, Michael A. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Aschner, Michael A. A1 - McLean, John A. A1 - Bowman, Aaron B. T1 - Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status JF - Metallomics N2 - Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity. KW - hallervorden-spatz-syndrome KW - mobility-mass spectrometry KW - energy-metabolism KW - coenzyme-a KW - model KW - neurotoxicity KW - glutathione KW - database KW - cells KW - neurodegeneration Y1 - 2015 U6 - https://doi.org/10.1039/C4MT00223G SN - 1756-591X SN - 1756-5901 VL - 7 SP - 363 EP - 370 PB - RSC Publ. CY - Cambridge ER - TY - GEN A1 - Kumar, Kevin K. A1 - Goodwin, Cody R. A1 - Uhouse, Michael A. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Aschner, Michael A. A1 - McLean, John A. A1 - Bowman, Aaron B. T1 - Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status N2 - Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 232 KW - cells KW - coenzyme-a KW - database KW - energy-metabolism KW - glutathione KW - hallervorden-spatz-syndrome KW - mobility-mass spectrometry KW - model KW - neurodegeneration KW - neurotoxicity Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-94314 SP - 363 EP - 370 ER - TY - JOUR A1 - Kumar, Kevin K. A1 - Goodwin, Cody R. A1 - Uhouse, Michael A. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Aschner, Michael A. A1 - McLean, John A. A1 - Bowman, Aaron B. T1 - Untargeted metabolic profiling identifies interactions between JF - Metallomics : integrated biometal science Y1 - 2015 U6 - https://doi.org/10.1039/c4mt00223g SN - 1756-5901 SN - 1756-591X VL - 7 IS - 2 SP - 363 EP - 370 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Köhler, Yvonne A1 - Luther, Eva Maria A1 - Meyer, Sören A1 - Schwerdtle, Tanja A1 - Dringen, Ralf T1 - Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes JF - Journal of trace elements in medicine and biology N2 - Inorganic arsenicals are environmental toxins that have been connected with neuropathies and impaired cognitive functions. To investigate whether such substances accumulate in brain astrocytes and affect their viability and glutathione metabolism, we have exposed cultured primary astrocytes to arsenite or arsenate. Both arsenicals compromised the cell viability of astrocytes in a time- and concentration-dependent manner. However, the early onset of cell toxicity in arsenite-treated astrocytes revealed the higher toxic potential of arsenite compared with arsenate. The concentrations of arsenite and arsenate that caused within 24 h half-maximal release of the cytosolic enzyme lactate dehydrogenase were around 0.3 mM and 10 mM, respectively. The cellular arsenic contents of astrocytes increased rapidly upon exposure to arsenite or arsenate and reached after 4 h of incubation almost constant steady state levels. These levels were about 3-times higher in astrocytes that had been exposed to a given concentration of arsenite compared with the respective arsenate condition. Analysis of the intracellular arsenic species revealed that almost exclusively arsenite was present in viable astrocytes that had been exposed to either arsenate or arsenite. The emerging toxicity of arsenite 4 h after exposure was accompanied by a loss in cellular total glutathione and by an increase in the cellular glutathione disulfide content. These data suggest that the high arsenite content of astrocytes that had been exposed to inorganic arsenicals causes an increase in the ratio of glutathione disulfide to glutathione which contributes to the toxic potential of these substances. KW - Arsenic KW - Astrocytes KW - GSH KW - Metabolism KW - Toxicity Y1 - 2014 U6 - https://doi.org/10.1016/j.jtemb.2014.04.007 SN - 0946-672X VL - 28 IS - 3 SP - 328 EP - 337 PB - Elsevier CY - Jena ER - TY - JOUR A1 - Li, Mingjun A1 - Gao, Lingyan A1 - Schlaich, Christoph A1 - Zhang, Jianguang A1 - Donskyi, Ievgen S. A1 - Yu, Guozhi A1 - Li, Wenzhong A1 - Tu, Zhaoxu A1 - Rolff, Jens A1 - Schwerdtle, Tanja A1 - Haag, Rainer A1 - Ma, Nan T1 - Construction of Functional Coatings with Durable and Broad-Spectrum Antibacterial Potential Based on Mussel-Inspired Dendritic Polyglycerol and in Situ-Formed Copper Nanoparticles JF - ACS applied materials & interfaces N2 - A novel surface coating with durable broad-spectrum antibacterial ability was prepared based on mussel inspired dendritic polyglycerol (MI-dPG) embedded with copper nanoparticles (Cu NPs). The functional surface coating is fabricated via a facile dip-coating process followed by in situ reduction of copper ions with a MI-dPG coating to introduce Cu NPs into the coating matrix. This coating has been demonstrated to possess efficient long-term antibacterial properties against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and kanamycin-resistant E. coli through an "attract-kill-release" strategy. The synergistic antibacterial activity of the coating was shown by the combination of two functions of the contact killing, reactive oxygen species production and Cu ions released from the coating. Furthermore, this coating inhibited biofilm formation and showed good compatibility to eukaryotic cells. Thus, this newly developed Cu NP-incorporated MI-dPG surface coating may find potential application in the design of antimicrobial coating, such as implantable devices. KW - Cu NP-incorporated MI-dPG coating KW - universal coating KW - in situ chemical reduction KW - antibacterial effect KW - drug-resistant bacteria Y1 - 2017 U6 - https://doi.org/10.1021/acsami.7b10541 SN - 1944-8244 VL - 9 SP - 35411 EP - 35418 PB - American Chemical Society CY - Washington 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 -