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  - 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  - Lohren, Hanna
A1  - Blagojevic, Lara
A1  - Fitkau, Romy
A1  - Ebert, Franziska
A1  - Schildknecht, Stefan
A1  - Leist, Marcel
A1  - Schwerdtle, Tanja
T1  - Toxicity of organic and inorganic mercury species in human neurons and human astrocytes
JF  - Journal of trace elements in medicine and biology
N2  - Organic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.
KW  - Methylmercury
KW  - Thiomersal
KW  - Mercuric mercury
KW  - Human differentiated neurons
KW  - Cytotoxicity
KW  - Apoptosis
Y1  - 2015
U6  - https://doi.org/10.1016/j.jtemb.2015.06.008
SN  - 0946-672X
VL  - 32
SP  - 200
EP  - 208
PB  - Elsevier
CY  - Jena
ER  - 
TY  - JOUR
A1  - Meyer, S.
A1  - Raber, G.
A1  - Ebert, Franziska
A1  - Leffers, L.
A1  - Müller, Sandra Marie
A1  - Taleshi, M. S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites
JF  - Toxicology research
N2  - 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.
Y1  - 2015
U6  - https://doi.org/10.1039/c5tx00122f
SN  - 2045-4538
VL  - 5
IS  - 4
SP  - 1289
EP  - 1296
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - GEN
A1  - Meyer, S.
A1  - Raber, G.
A1  - Ebert, Franziska
A1  - Leffers, L.
A1  - Müller, Sandra Marie
A1  - Taleshi, M. S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites
N2  - 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.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 199 
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-82008
ER  -