TY  - JOUR
A1  - Wandt, Viktoria Klara Veronika
A1  - Winkelbeiner, Nicola Lisa
A1  - Bornhorst, Julia
A1  - Witt, Barbara
A1  - Raschke, Stefanie
A1  - Simon, Luise
A1  - Ebert, Franziska
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A matter of concern
BT  - trace element dyshomeostasis and genomic stability in neurons
JF  - Redox Biology
N2  - Neurons are post-mitotic cells in the brain and their integrity is of central importance to avoid neurodegeneration. Yet, the inability of self-replenishment of post-mitotic cells results in the need to withstand challenges from numerous stressors during life. Neurons are exposed to oxidative stress due to high oxygen consumption during metabolic activity in the brain. Accordingly, DNA damage can occur and accumulate, resulting in genome instability. In this context, imbalances in brain trace element homeostasis are a matter of concern, especially regarding iron, copper, manganese, zinc, and selenium. Although trace elements are essential for brain physiology, excess and deficient conditions are considered to impair neuronal maintenance. Besides increasing oxidative stress, DNA damage response and repair of oxidative DNA damage are affected by trace elements. Hence, a balanced trace element homeostasis is of particular importance to safeguard neuronal genome integrity and prevent neuronal loss. This review summarises the current state of knowledge on the impact of deficient, as well as excessive iron, copper, manganese, zinc, and selenium levels on neuronal genome stability
Y1  - 2021
U6  - https://doi.org/10.1016/j.redox.2021.101877
VL  - 41
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
JF  - International Journal of Molecular Sciences
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186600
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - GEN
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1021 
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-484831
SN  - 1866-8372
IS  - 1021
ER  - 
TY  - JOUR
A1  - Müller, S. M.
A1  - Finke, Hannah
A1  - Ebert, Franziska
A1  - Kopp, Johannes Florian
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Francesconi, Kevin A.
A1  - Raber, G.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons
BT  - effects on gene expression, epigenetics, and biotransformation in HepG2 cells
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.
KW  - Arsenolipids
KW  - Gene expression
KW  - Arsenic-containing hydrocarbons
KW  - Global DNA methylation
KW  - Arsenic speciation
KW  - Metabolism
Y1  - 2018
U6  - https://doi.org/10.1007/s00204-018-2194-z
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 5
SP  - 1751
EP  - 1765
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Raber, Georg
A1  - Ebert, Franziska
A1  - Taleshi, Mojtaba S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons and arsenic-containing fatty acids: Transfer across and presystemic metabolism in the Caco-2 intestinal barrier model
JF  - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology
N2  - 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.
KW  - Arsenolipids
KW  - Caco-2 intestinal barrier model
KW  - Presystemic metabolism
KW  - Toxicity
Y1  - 2015
U6  - https://doi.org/10.1002/mnfr.201500286
SN  - 1613-4125
SN  - 1613-4133
VL  - 59
IS  - 10
SP  - 2044
EP  - 2056
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Schulz, J.
A1  - Jeibmann, A.
A1  - Taleshi, M. S.
A1  - Ebert, Franziska
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster
JF  - Metallomics : integrated biometal science
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.
Y1  - 2014
U6  - https://doi.org/10.1039/c4mt00249k
SN  - 1756-5901
SN  - 1756-591X
VL  - 6
IS  - 11
SP  - 2010
EP  - 2014
PB  - Royal Society of Chemistry
CY  - Cambridge
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  - JOUR
A1  - Müller, Sandra Marie
A1  - Ebert, Franziska
A1  - Bornhorst, Julia
A1  - Galla, Hans-Joachim
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal fluid barrier
JF  - Journal of trace elements in medicine and biology
N2  - Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention in the last few years because of their presence in many seafoods and reports showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in vitro studies indicate that some arsenolipids might have adverse effects on brain health. In the present study, we focused on the effects of selected arsenolipids and three representative metabolites on the blood-cerebrospinal fluid barrier (B-CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs) with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo-dimethylpropanoic acid) to examine their cytotoxic potential and impact on barrier integrity. The toxic arsenic species arsenite was also tested in this way and served as a reference substance. While AsFAs and the metabolites showed no cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity, being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF-B integrity showed a concentration dependent disruption of the barrier within 72 h. The correlation with the decreased plasma membrane surface area (measured as capacitance) indicates cytotoxic effects. These findings suggest exposure to elevated levels of certain arsenolipids may have detrimental consequences for the central nervous system.
KW  - Arsenolipids
KW  - Blood-liquor barrier
KW  - Blood-cerebrospinal fluid barrier
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
Y1  - 2018
U6  - https://doi.org/10.1016/j.jtemb.2018.01.020
SN  - 0946-672X
VL  - 49
SP  - 171
EP  - 177
PB  - Elsevier GMBH
CY  - München
ER  - 
TY  - JOUR
A1  - Witt, B.
A1  - Bornhorst, Julia
A1  - Mitze, H.
A1  - Ebert, Franziska
A1  - Meyer, S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenolipids exert less toxicity in a human neuron astrocyte co-culture as compared to the respective monocultures
JF  - Metallomics : integrated biometal science
N2  - Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have recently been shown to exert toxic effects in human neurons. In this study we assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the high cellular accessibility and substantial toxicity observed astrocytes were identified as further potential brain target cells for arsenolipids. Thereby, the AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to arsenite. Next we compared the toxicity of the arsenicals in a co-culture model of the respective human astrocytes and neurons. Notably the AsHCs did not show any substantial toxic effects in the co-culture, while arsenite did. The arsenic accessibility studies indicated that in the co-culture astrocytes protect neurons against cellular arsenic accumulation especially after incubation with arsenolipids. In summary, these data underline the importance of the glial-neuron interaction when assessing the in vitro neurotoxicity of new unclassified metal species.
Y1  - 2017
U6  - https://doi.org/10.1039/c7mt00036g
SN  - 1756-5901
SN  - 1756-591X
VL  - 9
SP  - 442
EP  - 446
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Witt, Barbara
A1  - Ebert, Franziska
A1  - Meyer, Sören
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons
JF  - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology
N2  - 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.
KW  - Arsenic-containing fatty acids
KW  - Arsenic-containing hydrocarbons
KW  - Arsenite
KW  - Arsenolipids
KW  - Neurodevelopmental toxicity
Y1  - 2017
U6  - https://doi.org/10.1002/mnfr.201700199
SN  - 1613-4125
SN  - 1613-4133
VL  - 61
PB  - Wiley
CY  - Hoboken
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  - Witt, Barbara
A1  - Stiboller, Michael
A1  - Raschke, Stefanie
A1  - Friese, Sharleen
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
T1  - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers
JF  - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS
N2  - 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.
KW  - Copper
KW  - Astrocytes
KW  - Toxicity
KW  - Mitochondria
KW  - ROS
KW  - Trace elements
Y1  - 2021
U6  - https://doi.org/10.1016/j.jtemb.2021.126711
SN  - 1878-3252
VL  - 65
PB  - Elsevier
CY  - München
ER  - 
TY  - JOUR
A1  - Michaelis, Vivien
A1  - Aengenheister, Leonie
A1  - Tuchtenhagen, Max
A1  - Rinklebe, Jörg
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
A1  - Buerki-Thurnherr, Tina
A1  - Bornhorst, Julia
T1  - Differences and interactions in placental manganese and iron transfer across an in vitro model of human villous trophoblasts
JF  - International journal of molecular sciences
N2  - 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.
KW  - manganese
KW  - iron
KW  - placental transfer
KW  - TE interactions
KW  - BeWo b30
KW  - trophoblasts
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23063296
SN  - 1422-0067
VL  - 23
IS  - 6
PB  - MDPI
CY  - Basel
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  - Müller, Sandra Marie
A1  - Ebert, Franziska
A1  - Raber, Georg
A1  - Meyer, Sören
A1  - Bornhorst, Julia
A1  - Hüwel, Stephan
A1  - Galla, Hans-Joachim
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Effects of arsenolipids on in vitro blood-brain barrier model
JF  - Archives of toxicology : official journal of EUROTOX
N2  - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood–brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood–brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood–brain barrier). AsHCs exerted the strongest cytotoxic effects of all investigated arsenicals as they were up to fivefold more potent than the toxic reference species arsenite (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332 across the BBB after 6 h at concentrations that do not affect the barrier integrity. Furthermore, incubation with AsHCs for 72 h led to a disruption of the barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical staining of three tight junction proteins revealed a significant impact on the cell membrane. Because AsHCs enhance the permeability of the in vitro blood–brain barrier, a similar behavior in an in vivo system cannot be excluded. Consequently, AsHCs might facilitate the transfer of accompanying foodborne toxicants into the brain.
KW  - Arsenolipids
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
KW  - In vitro blood-brain barrier model
Y1  - 2017
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 2
SP  - 823
EP  - 832
PB  - Springer
CY  - Heidelberg
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  - 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  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Raber, Georg
A1  - Ebert, Franziska
A1  - Leffers, L.
A1  - Mueller, Sandra Maria
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 (DMA(V), 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 mu M concentrations. DMA(V) causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMA(V) 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  - 2045-452X
SN  - 2045-4538
VL  - 4
IS  - 5
SP  - 1289
EP  - 1296
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  -