TY - JOUR A1 - Taleshi, Mojtaba S. A1 - Seidler-Egdal, Rune K. A1 - Jensen, Kenneth Bendix A1 - Schwerdtle, Tanja A1 - Francesconi, Kevin A. T1 - Synthesis and Characterization of Arsenolipids: Naturally Occurring Arsenic Compounds in Fish and Algae JF - Organometallics N2 - Arsenic-containing lipids (arsenolipids) are natural products present in fish and algae. Because these compounds occur in foods, there is considerable interest in their human toxicology. We report the synthesis and characterization of seven arsenic-containing lipids, including six natural products. The compounds comprise dimethylarsinyl groups attached to saturated long-chain hydrocarbons (three compounds), saturated long-chain fatty acids (two compounds), and monounsaturated long chain fatty acids (two compounds). The arsenic group was introduced through sodium dimethylarsenide or bis(dimethylarsenic) oxide. The latter route provided higher and more reproducible yields, and consequently, this pathway was followed to synthesize six of the seven compounds. Mass spectral properties are described to assist in the identification of these compounds in natural samples. The pure synthesized arsenolipids will be used for in vitro experiments with human cells to test their uptake, biotransformation, and possible toxic effects. Y1 - 2014 U6 - https://doi.org/10.1021/om4011092 SN - 0276-7333 SN - 1520-6041 VL - 33 IS - 6 SP - 1397 EP - 1403 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Wehe, Christoph A. A1 - Pieper, Imke A1 - Holtkamp, Michael A1 - Thyssen, Georgina M. A1 - Sperling, Michael A1 - Schwerdtle, Tanja A1 - Karst, Uwe T1 - On-line species-unspecific isotope dilution analysis in the picomolar range reveals the time- and species-depending mercury uptake in human astrocytes JF - Analytical & bioanalytical chemistry N2 - In order to reveal the time-depending mercury species uptake by human astrocytes, a novel approach for total mercury analysis is presented, which uses an accelerated sample introduction system combined on-line with an inductively coupled plasma mass spectrometer equipped with a collision/reaction cell. Human astrocyte samples were incubated with inorganic mercury (HgCl2), methylmercury chloride (MeHgCl), and thimerosal. After 1-h incubation with Hg2+, cellular concentrations of 3 mu M were obtained, whereas for organic species, concentrations of 14-18 mu M could be found. After 24 h, a cellular accumulation factor of 0.3 was observed for the cells incubated with Hg2+, whereas the organic species both showed values of about 5. Due to the obtained steady-state signals, reliable results with relative standard deviations of well below 5 % and limits of detection in the concentration range of 1 ng L-1 were obtained using external calibration and species-unspecific isotope dilution analysis approaches. The results were further validated using atomic fluorescence spectrometry. KW - Mercury KW - Thimerosal KW - Astrocytes KW - ICP-MS KW - Isotope dilution analysis KW - Automation Y1 - 2014 U6 - https://doi.org/10.1007/s00216-013-7608-4 SN - 1618-2642 SN - 1618-2650 VL - 406 IS - 7 SP - 1909 EP - 1916 PB - Springer CY - Heidelberg ER - TY - GEN A1 - Meyer, Sören A1 - Schulz, Jacqueline A1 - Jeibmann, Astrid A1 - Taleshi, Mojtaba S. A1 - Ebert, Franziska A1 - Francesconi, Kevin A1 - Schwerdtle, Tanja T1 - Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster N2 - Arsenic-containing hydrocarbons (AsHC) constitute one group of arsenolipids that have been identified in seafood. In this first in vivo toxicity study for AsHCs, we show that AsHCs exert toxic effects in Drosophila melanogaster in a concentration range similar to that of arsenite. In contrast to arsenite, however, AsHCs cause developmental toxicity in the late developmental stages of Drosophila melanogaster. This work illustrates the need for a full characterisation of the toxicity of AsHCs in experimental animals to finally assess the risk to human health related to the presence of arsenolipids in seafood. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 183 KW - cod-liver KW - arsenolipids present KW - fatty-acids KW - rp-hplc KW - identification KW - fish KW - oil Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-76819 VL - 11 IS - 6 SP - 2010 EP - 2014 ER - TY - JOUR A1 - Meyer, Sören A1 - Schulz, Jacqueline A1 - Jeibmann, Astrid A1 - Taleshi, Mojtaba S. A1 - Ebert, Franziska A1 - Francesconi, Kevin A1 - Schwerdtle, Tanja ED - Schwerdtle, Tanja T1 - Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster JF - Metallomics N2 - Arsenic-containing hydrocarbons (AsHC) constitute one group of arsenolipids that have been identified in seafood. In this first in vivo toxicity study for AsHCs, we show that AsHCs exert toxic effects in Drosophila melanogaster in a concentration range similar to that of arsenite. In contrast to arsenite, however, AsHCs cause developmental toxicity in the late developmental stages of Drosophila melanogaster. This work illustrates the need for a full characterisation of the toxicity of AsHCs in experimental animals to finally assess the risk to human health related to the presence of arsenolipids in seafood. KW - arsenolipids present KW - cod-liver KW - fatty-acids KW - identification KW - rp-hplc KW - fish KW - oil Y1 - 2014 SN - 1756-5901 SP - 2010 EP - 2014 PB - The Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Mayer, Lena S. A1 - Uciechowski, Peter A1 - Meyer, Sören A1 - Schwerdtle, Tanja A1 - Rink, Lothar A1 - Haase, Hajo T1 - Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes N2 - Zinc deficiency has a fundamental influence on the immune defense, with multiple effects on different immune cells, resulting in a major impairment of human health. Monocytes and macrophages are among the immune cells that are most fundamentally affected by zinc, but the impact of zinc on these cells is still far from being completely understood. Therefore, this study investigates the influence of zinc deficiency on monocytes of healthy human donors. Peripheral blood mononuclear cells, which include monocytes, were cultured under zinc deficient conditions for 3 days. This was achieved by two different methods: by application of the membrane permeable chelator N,N,N0´,N0´-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) or by removal of zinc from the culture medium using a CHELEX 100 resin. Subsequently, monocyte functions were analyzed in response to Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Zinc depletion had differential effects. On the one hand, elimination of bacterial pathogens by phagocytosis and oxidative burst was elevated. On the other hand, the production of the inflammatory cytokines tumor necrosis factor (TNF)-a and interleukin (IL)-6 was reduced. This suggests that monocytes shift from intercellular communication to basic innate defensive functions in response to zinc deficiency. These results were obtained regardless of the method by which zinc deficiency was achieved. However, CHELEX-treated medium strongly augmented cytokine production, independently from its capability for zinc removal. This side-effect severely limits the use of CHELEX for investigating the effects of zinc deficiency on innate immunity. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 281 Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-99405 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 - Pieper, Imke A1 - Wehe, Christoph A. A1 - Bornhorst, Julia A1 - Ebert, Franziska A1 - Leffers, Larissa A1 - Holtkamp, Michael A1 - Höseler, Pia A1 - Weber, Till A1 - Mangerich, Aswin A1 - Bürkle, Alexander A1 - Karst, Uwe A1 - Schwerdtle, Tanja T1 - Mechanisms of Hg species induced toxicity in cultured human astrocytes BT - genotoxicity and DNA-damage response JF - Metallomics N2 - The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity. KW - cell-death KW - poly(ADP-ribose) polymerase-1 KW - neurodegenerative diseases KW - adduct formation KW - thimerosal KW - methylmercury KW - repair KW - neurotoxicity KW - manganese KW - exposure Y1 - 2014 U6 - https://doi.org/10.1039/c3mt00337j SN - 1756-591X SN - 1756-5901 VL - 2014 IS - 6 SP - 662 EP - 671 ER - TY - JOUR A1 - Pieper, Imke A1 - Wehe, Christoph A. A1 - Bornhorst, Julia A1 - Ebert, Franziska A1 - Leffers, Larissa A1 - Holtkamp, Michael A1 - Hoeseler, Pia A1 - Weber, Till A1 - Mangerich, Aswin A1 - Buerkle, Alexander A1 - Karst, Uwe A1 - Schwerdtle, Tanja T1 - Mechanisms of Hg species induced toxicity in cultured human astrocytes: genotoxicity and DNA-damage response JF - Metallomics : integrated biometal science N2 - The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co- genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl) ation contributes to organic Hg induced neurotoxicity. Y1 - 2014 U6 - https://doi.org/10.1039/c3mt00337j SN - 1756-5901 SN - 1756-591X VL - 6 IS - 3 SP - 662 EP - 671 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Pieper, Imke A1 - Wehe, Christoph A. A1 - Bornhorst, Julia A1 - Ebert, Franziska A1 - Leffers, Larissa A1 - Holtkamp, Michael A1 - Höseler, Pia A1 - Weber, Till A1 - Mangerich, Aswin A1 - Bürkle, Alexander A1 - Karst, Uwe A1 - Schwerdtle, Tanja T1 - Mechanisms of Hg species induced toxicity in cultured human astrocytes BT - genotoxicity and DNA-damage response N2 - The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co- genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl) ation contributes to organic Hg induced neurotoxicity. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 171 KW - adduct formation KW - cell-death KW - exposure KW - manganese KW - methylmercury KW - neurodegenerative diseases KW - neurotoxicity KW - poly(ADP-ribose) polymerase-1 KW - repair KW - thimerosal Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-74379 SP - 662 EP - 671 ER -