@article{WittEbertMeyeretal.2017, author = {Witt, Barbara and Ebert, Franziska and Meyer, S{\"o}ren and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons}, series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, volume = {61}, journal = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, publisher = {Wiley}, address = {Hoboken}, issn = {1613-4125}, doi = {10.1002/mnfr.201700199}, pages = {10}, year = {2017}, abstract = {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.}, language = {en} } @article{WittMeyerEbertetal.2017, author = {Witt, Barbara and Meyer, S{\"o}ren and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {91}, journal = {Archives of toxicology : official journal of EUROTOX}, publisher = {Springer}, address = {Heidelberg}, issn = {0340-5761}, doi = {10.1007/s00204-017-1933-x}, pages = {3121 -- 3134}, year = {2017}, abstract = {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.}, language = {en} } @article{TaylorGoodaleRaabetal.2017, author = {Taylor, Vivien and Goodale, Britton and Raab, Andrea and Schwerdtle, Tanja and Reimer, Ken and Conklin, Sean and Karagas, Margaret R. and Francesconi, Kevin A.}, title = {Human exposure to organic arsenic species from seafood}, series = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man}, volume = {580}, journal = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0048-9697}, doi = {10.1016/j.scitotenv.2016.12.113}, pages = {266 -- 282}, year = {2017}, abstract = {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.}, language = {en} } @article{MeyerLopezSerranoMitzeetal.2017, author = {Meyer, S{\"o}ren and Lopez-Serrano, Aniceto and Mitze, Hanna and Jakubowski, Norbert and Schwerdtle, Tanja}, title = {Single-cell analysis by ICP-MS/MS as a fast tool for cellular bioavailability studies of arsenite}, series = {Metallomics : integrated biometal science}, volume = {10}, journal = {Metallomics : integrated biometal science}, number = {1}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c7mt00285h}, pages = {73 -- 76}, year = {2017}, abstract = {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.}, language = {en} } @article{KroepflMarschallFrancesconietal.2017, author = {Kr{\"o}pfl, Nina and Marschall, Talke A. and Francesconi, Kevin A. and Schwerdtle, Tanja and Kuehnelt, Doris}, title = {Quantitative determination of the sulfur-containing antioxidant ergothioneine by HPLC/ICP- QQQ-MS}, series = {Journal of Analytical Atomic Spectrometry}, volume = {32}, journal = {Journal of Analytical Atomic Spectrometry}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {0267-9477}, doi = {10.1039/c7ja00030h}, pages = {1571 -- 1581}, year = {2017}, abstract = {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.}, language = {en} } @misc{DuyduBasaranAydinetal.2017, author = {Duydu, Yalcin and Basaran, Nursen and Aydin, Sevtap and Ustundag, Aylin and Goktas, Hatica Gul and Yalcin, Can {\"O}zg{\"u}r and Bacanli, Merve and Sarigol, Zehra and Aydos, Kaan and Atabekoglu, Cem Somer and Schwerdtle, Tanja and Golka, Klaus and Ickstadt, Katja and Bolt, Hermann M.}, title = {Investigation of boron mediated reproductive and developmental effects in highly boron exposed population}, series = {Toxicology letters}, volume = {280}, journal = {Toxicology letters}, publisher = {Elsevier}, address = {Clare}, issn = {0378-4274}, doi = {10.1016/j.toxlet.2017.07.259}, pages = {S94 -- S94}, year = {2017}, language = {en} } @article{LiGaoSchlaichetal.2017, author = {Li, Mingjun and Gao, Lingyan and Schlaich, Christoph and Zhang, Jianguang and Donskyi, Ievgen S. and Yu, Guozhi and Li, Wenzhong and Tu, Zhaoxu and Rolff, Jens and Schwerdtle, Tanja and Haag, Rainer and Ma, Nan}, title = {Construction of Functional Coatings with Durable and Broad-Spectrum Antibacterial Potential Based on Mussel-Inspired Dendritic Polyglycerol and in Situ-Formed Copper Nanoparticles}, series = {ACS applied materials \& interfaces}, volume = {9}, journal = {ACS applied materials \& interfaces}, publisher = {American Chemical Society}, address = {Washington}, issn = {1944-8244}, doi = {10.1021/acsami.7b10541}, pages = {35411 -- 35418}, year = {2017}, abstract = {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.}, language = {en} } @article{FredeEbertKippetal.2017, author = {Frede, Katja and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja and Baldermann, Susanne}, title = {Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells}, series = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, volume = {65}, journal = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, publisher = {American Chemical Society}, address = {Washington}, issn = {0021-8561}, doi = {10.1021/acs.jafc.7b01929}, pages = {5944 -- 5952}, year = {2017}, abstract = {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.}, language = {en} } @article{StrehlauWeberLuerenbaumetal.2017, author = {Strehlau, Jenny and Weber, Till and Luerenbaum, Constantin and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja and Winter, Martin and Nowak, Sascha}, title = {Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials}, series = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica}, volume = {409}, journal = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica}, publisher = {Springer}, address = {Heidelberg}, issn = {1618-2642}, doi = {10.1007/s00216-017-0549-6}, pages = {6123 -- 6131}, year = {2017}, abstract = {A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9\%. It could be shown that no matrix effects were present and recovery rates between 98 and 104\% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place.}, language = {en} } @misc{AschnerPalinskiSperlingetal.2017, author = {Aschner, Michael A. and Palinski, Catherine and Sperling, Michael and Karst, U. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Imaging metals in Caenorhabditis elegans}, series = {Metallomics : integrated biometal science}, volume = {9}, journal = {Metallomics : integrated biometal science}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c6mt00265j}, pages = {357 -- 364}, year = {2017}, abstract = {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).}, language = {en} }