@article{WittStibollerRaschkeetal.2021, author = {Witt, Barbara and Stiboller, Michael and Raschke, Stefanie and Friese, Sharleen and Ebert, Franziska and Schwerdtle, Tanja}, title = {Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers}, series = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS}, volume = {65}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS}, publisher = {Elsevier}, address = {M{\"u}nchen}, issn = {1878-3252}, doi = {10.1016/j.jtemb.2021.126711}, pages = {9}, year = {2021}, abstract = {Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.}, language = {en} } @article{LiebigMorenoThuenemannetal.2018, author = {Liebig, Ferenc and Moreno, Silvia and Thuenemann, Andreas F. and Temme, Achim and Appelhans, Dietmar and Koetz, Joachim}, title = {Toxicological investigations of "naked" and polymer-entrapped AOT-based gold nanotriangles}, series = {Colloids and surfaces : an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin ; B, Biointerfaces}, volume = {167}, journal = {Colloids and surfaces : an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin ; B, Biointerfaces}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0927-7765}, doi = {10.1016/j.colsurfb.2018.04.059}, pages = {560 -- 567}, year = {2018}, abstract = {Negatively charged ultrathin gold nanotriangles (AuNTs) were synthesized in a vesicular dioctyl sodium sulfosuccinate (AOT)/phospholipid-based template phase. These "naked" AuNTs with localized surface plasmon resonances in the NIR region at about 1300 nm and special photothermal properties are of particular interest for imaging and hyperthermia of cancerous tissues. For these kinds of applications the toxicity and the cellular uptake of the AuNTs is of outstanding importance. Therefore, this study focuses on the toxicity of "naked" AOT-stabilized AuNTs compared to polymer-coated AuNTs. Polymeric coating consisted of non-modified hyperbranched poly(ethyleneimine) (PEI), maltose-modified poly(ethyleneimine) (PEI-Mal) and heparin. The toxicological experiments were carried out with two different cell lines (embryonic kidney carcinoma cell line HEK293T and NK-cell leukemia cell line YTS). This study revealed that the heparin-coating of AuNTs improved biocompatibility by a factor of 50 when compared to naked AuNTs. Of note, the highest nontoxic concentration of the AuNTs coated with PEI and PEI-Mal is drastically decreased. Overall, this is mainly triggered by the different surface charges of polymeric coatings. Therefore, AuNTs coated with heparin were selected to carry out uptake studies. Their promising high biocompatibility and cellular uptake may open future studies in the field of biomedical applications. (C) 2018 Elsevier B.V. All rights reserved.}, language = {en} } @article{EbertMeyerLeffersetal.2016, author = {Ebert, Franziska and Meyer, S{\"o}ren and Leffers, Larissa and Raber, Georg and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Toxicological characterisation of a thio-arsenosugar-glycerol in human cells}, series = {Journal of trace elements in medicine and biology}, volume = {38}, journal = {Journal of trace elements in medicine and biology}, publisher = {Springer Publishing Company}, address = {Jena}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2016.04.013}, pages = {150 -- 156}, year = {2016}, abstract = {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.}, language = {en} } @article{CzolkosDockTonningetal.2016, author = {Czolkos, Ilja and Dock, Eva and Tonning, Erik and Christensen, Jakob and Winther-Nielsen, Margrethe and Carlsson, Charlotte and Mojzikova, Renata and Skladal, Petr and Wollenberger, Ursula and Norgaard, Lars and Ruzgas, Tautgirdas and Emneus, Jenny}, title = {Prediction of wastewater quality using amperometric bioelectronic tongues}, series = {Marine policy}, volume = {75}, journal = {Marine policy}, publisher = {Elsevier}, address = {Oxford}, issn = {0956-5663}, doi = {10.1016/j.bios.2015.08.055}, pages = {375 -- 382}, year = {2016}, abstract = {Wastewater samples from a Swedish chemi-thermo-mechanical pulp (CTMP) mill collected at different purification stages in a wastewater treatment plant (WWTP) were analyzed with an amperometric enzyme-based biosensor array in a flow-injection system. In order to resolve the complex composition of the wastewater, the array consists of several sensing elements which yield a multidimensional response. We used principal component analysis (PCA) to decompose the array's responses, and found that wastewater with different degrees of pollution can be differentiated. With the help of partial least squares regression (PLS-R), we could link the sensor responses to the toxicity parameter, as well as to global organic pollution parameters (COD, BOD, and TOC). From investigating the influences of individual sensors in the array, it was found that the best models were in most cases obtained when all sensors in the array were included in the PLS-R model. We find that fast simultaneous determination of several global environmental parameters characterizing wastewaters is possible with this kind of biosensor array, in particular because of the link between the sensor responses and the biological effect onto the ecosystem into which the wastewater would be released. In conjunction with multivariate data analysis tools, there is strong potential to reduce the total time until a result is yielded from days to a few minutes.}, language = {en} } @article{MeyerRaberEbertetal.2015, author = {Meyer, S{\"o}ren and Raber, Georg and Ebert, Franziska and Taleshi, Mojtaba S. and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Arsenic-containing hydrocarbons and arsenic-containing fatty acids: Transfer across and presystemic metabolism in the Caco-2 intestinal barrier model}, series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, volume = {59}, journal = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, number = {10}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1613-4125}, doi = {10.1002/mnfr.201500286}, pages = {2044 -- 2056}, year = {2015}, abstract = {Scope: Arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) represent two classes of arsenolipids occurring naturally in marine food. Toxicological data are yet scarce and an assessment regarding the risk to human health has not been possible. Here, we investigated the transfer and presystemic metabolism of five arsenolipids in an intestinal barrier model. Methods and results: Three AsHCs and two AsFAs were applied to the Caco-2 intestinal barrier model. Thereby, the short-chain AsHCs reached up to 50\% permeability. Transport is likely to occur via passive diffusion. The AsFAs showed lower intestinal bioavailability, but respective permeabilities were still two to five times higher as compared to arsenobetaine or arsenosugars. Interestingly, AsFAs were effectively biotransformed while passing the in vitro intestinal barrier, whereas AsHCs were transported to the blood-facing compartment essentially unchanged. Conclusion: AsFAs can be presystemically metabolised and the amount of transferred arsenic is lower than that for AsHCs. In contrast, AsHCs are likely to be highly intestinally bioavailable to humans. Since AsHCs exert strong toxicity in vitro and in vivo, toxicity studies with experimental animals as well as a human exposure assessment are needed to assess the risk to human health related to the presence of AsHCs in seafood.}, language = {en} } @article{KoehlerLutherMeyeretal.2014, author = {K{\"o}hler, Yvonne and Luther, Eva Maria and Meyer, S{\"o}ren and Schwerdtle, Tanja and Dringen, Ralf}, title = {Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes}, series = {Journal of trace elements in medicine and biology}, volume = {28}, journal = {Journal of trace elements in medicine and biology}, number = {3}, publisher = {Elsevier}, address = {Jena}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2014.04.007}, pages = {328 -- 337}, year = {2014}, abstract = {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.}, language = {en} }