@misc{MeyerSchulzJeibmannetal.2014, author = {Meyer, S{\"o}ren and Schulz, Jacqueline and Jeibmann, Astrid and Taleshi, Mojtaba S. and Ebert, Franziska and Francesconi, Kevin and Schwerdtle, Tanja}, title = {Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster}, volume = {11}, number = {6}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-76819}, pages = {2010 -- 2014}, year = {2014}, abstract = {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.}, language = {en} } @article{MeyerSchulzJeibmannetal.2014, author = {Meyer, S{\"o}ren and Schulz, Jacqueline and Jeibmann, Astrid and Taleshi, Mojtaba S. and Ebert, Franziska and Francesconi, Kevin and Schwerdtle, Tanja}, title = {Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster}, series = {Metallomics}, journal = {Metallomics}, editor = {Schwerdtle, Tanja}, publisher = {The Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, pages = {2010 -- 2014}, year = {2014}, abstract = {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.}, language = {en} } @article{EbertZiemannWandtetal.2020, author = {Ebert, Franziska and Ziemann, Vanessa and Wandt, Viktoria Klara Veronika and Witt, Barbara and M{\"u}ller, Sandra Marie and Guttenberger, Nikolaus and Bankoglu, Ezgi Eyluel and Stopper, Helga and Raber, Georg and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Cellular toxicological characterization of a thioxolated arsenic-containing hydrocarbon}, series = {Journal of trace elements in medicine and biology}, volume = {61}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier}, address = {M{\"u}nchen}, doi = {10.1016/j.jtemb.2020.126563}, year = {2020}, abstract = {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.}, language = {en} } @article{MichaelisAengenheisterTuchtenhagenetal.2022, author = {Michaelis, Vivien and Aengenheister, Leonie and Tuchtenhagen, Max and Rinklebe, J{\"o}rg and Ebert, Franziska and Schwerdtle, Tanja and Buerki-Thurnherr, Tina and Bornhorst, Julia}, title = {Differences and interactions in placental manganese and iron transfer across an in vitro model of human villous trophoblasts}, series = {International journal of molecular sciences}, volume = {23}, journal = {International journal of molecular sciences}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms23063296}, pages = {18}, year = {2022}, abstract = {Manganese (Mn) as well as iron (Fe) are essential trace elements (TE) important for the maintenance of physiological functions including fetal development. However, in the case of Mn, evidence suggests that excess levels of intrauterine Mn are associated with adverse pregnancy outcomes. Although Mn is known to cross the placenta, the fundamentals of Mn transfer kinetics and mechanisms are largely unknown. Moreover, exposure to combinations of TEs should be considered in mechanistic transfer studies, in particular for TEs expected to share similar transfer pathways. Here, we performed a mechanistic in vitro study on the placental transfer of Mn across a BeWo b30 trophoblast layer. Our data revealed distinct differences in the placental transfer of Mn and Fe. While placental permeability to Fe showed a clear inverse dose-dependency, Mn transfer was largely independent of the applied doses. Concurrent exposure of Mn and Fe revealed transfer interactions of Fe and Mn, indicating that they share common transfer mechanisms. In general, mRNA and protein expression of discussed transporters like DMT1, TfR, or FPN were only marginally altered in BeWo cells despite the different exposure scenarios highlighting that Mn transfer across the trophoblast layer likely involves a combination of active and passive transport processes.}, language = {en} } @article{FinkeWinkelbeinerLossowetal.2020, author = {Finke, Hannah and Winkelbeiner, Nicola Lisa and Lossow, Kristina and Hertel, Barbara and Wandt, Viktoria Klara Veronika and Schwarz, Maria and Pohl, Gabriele and Kopp, Johannes Florian and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja}, title = {Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice}, series = {Molecular nutrition \& food research}, volume = {64}, journal = {Molecular nutrition \& food research}, number = {16}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1613-4125}, doi = {10.1002/mnfr.202000325}, year = {2020}, abstract = {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.}, language = {en} } @article{MeyerRaberEbertetal.2015, author = {Meyer, S. and Raber, G. and Ebert, Franziska and Leffers, L. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites}, series = {Toxicology research}, volume = {5}, journal = {Toxicology research}, number = {4}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2045-4538}, doi = {10.1039/c5tx00122f}, pages = {1289 -- 1296}, year = {2015}, abstract = {Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.}, language = {en} } @misc{MeyerRaberEbertetal.2015, author = {Meyer, S. and Raber, G. and Ebert, Franziska and Leffers, L. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-82008}, year = {2015}, abstract = {Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.}, language = {en} } @article{MeyerMatissekMuelleretal.2014, author = {Meyer, S{\"o}ren and Matissek, M. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {In vitro toxicological characterisation of three arsenic-containing hydrocarbons}, series = {Metallomics}, volume = {2014}, journal = {Metallomics}, number = {6}, issn = {1756-591X}, doi = {10.1039/c4mt00061g}, pages = {1023 -- 1033}, year = {2014}, abstract = {Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.}, language = {en} } @misc{MeyerMatissekMuelleretal.2014, author = {Meyer, S{\"o}ren and Matissek, M. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {In vitro toxicological characterisation of three arsenic-containing hydrocarbons}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-74201}, pages = {1023 -- 1033}, year = {2014}, abstract = {Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.}, language = {en} } @article{PieperWeheBornhorstetal.2014, author = {Pieper, Imke and Wehe, Christoph A. and Bornhorst, Julia and Ebert, Franziska and Leffers, Larissa and Holtkamp, Michael and H{\"o}seler, Pia and Weber, Till and Mangerich, Aswin and B{\"u}rkle, Alexander and Karst, Uwe and Schwerdtle, Tanja}, title = {Mechanisms of Hg species induced toxicity in cultured human astrocytes}, series = {Metallomics}, volume = {2014}, journal = {Metallomics}, number = {6}, issn = {1756-591X}, doi = {10.1039/c3mt00337j}, pages = {662 -- 671}, year = {2014}, abstract = {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.}, language = {en} }