TY - JOUR A1 - Knoche, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - LC-HRMS-Based identification of transformation products of the drug salinomycin generated by electrochemistry and liver microsome JF - Antibiotics N2 - The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction. KW - salinomycin KW - ionophore antibiotics KW - transformation product KW - electrochemistry KW - rat KW - human liver microsomes KW - HRMS Y1 - 2022 U6 - https://doi.org/10.3390/antibiotics11020155 SN - 2079-6382 VL - 11 IS - 2 PB - MDPI CY - Basel ER - TY - JOUR A1 - Nicolai, Merle Marie A1 - Witt, Barbara A1 - Friese, Sharleen A1 - Michaelis, Vivien A1 - Hölz-Armstrong, Lisa A1 - Martin, Maximilian A1 - Ebert, Franziska A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells JF - Food and chemical toxicology N2 - Manganese (Mn) is an essential trace element, but overexposure is associated with toxicity and neurological dysfunction. Accumulation of Mn can be observed in dopamine-rich regions of the brain in vivo and Mn-induced oxidative stress has been discussed extensively. Nevertheless, Mn-induced DNA damage, adverse effects of DNA repair, and possible resulting consequences for the neurite network are not yet characterized. For this, LUHMES cells were used, as they differentiate into dopaminergic-like neurons and form extensive neurite networks. Experiments were conducted to analyze Mn bioavailability and cytotoxicity of MnCl2, indicating a dose-dependent uptake and substantial cytotoxic effects. DNA damage, analyzed by means of 8-oxo-7,8-dihydro-2'-guanine (8oxodG) and single DNA strand break formation, showed significant dose- and time-dependent increase of DNA damage upon 48 h Mn exposure. Furthermore, the DNA damage response was increased which was assessed by analytical quantification of poly(ADP-ribosyl)ation (PARylation). Gene expression of the respective DNA repair genes was not significantly affected. Degradation of the neuronal network is significantly altered by 48 h Mn exposure. Altogether, this study contributes to the characterization of Mn-induced neurotoxicity, by analyzing the adverse effects of Mn on genome integrity in dopaminergic-like neurons and respective outcomes. KW - Manganese KW - Dopaminergic neurons KW - DNA integrity KW - DNA repair KW - Neurodegeneration KW - Oxidative stress KW - Genotoxicity Y1 - 2022 U6 - https://doi.org/10.1016/j.fct.2022.112822 SN - 0278-6915 SN - 1873-6351 VL - 161 PB - Elsevier CY - Oxford 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 - Ijomone, Omamuyovwi M. A1 - Iroegbu, Joy D. A1 - Morcillo, Patricia A1 - Ayodele, Akinyemi J. A1 - Ijomone, Olayemi K. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Aschner, Michael T1 - Sex-dependent metal accumulation and immunoexpression of Hsp70 and Nrf2 in rats' brain following manganese exposure JF - Environmental toxicology N2 - Manganese (Mn), although important for multiple cellular processes, has posed environmental health concerns due to its neurotoxic effects. In recent years, there have been extensive studies on the mechanism of Mn-induced neuropathology, as well as the sex-dependent vulnerability to its neurotoxic effects. Nonetheless, cellular mechanisms influenced by sex differences in susceptibility to Mn have yet to be adequately characterized. Since oxidative stress is a key mechanism of Mn neurotoxicity, here, we have probed Hsp70 and Nrf2 proteins to investigate the sex-dependent changes following exposure to Mn. Male and female rats were administered intraperitoneal injections of MnCl2 (10 mg/kg and 25 mg/kg) 48 hourly for a total of eight injections (15 days). We evaluated changes in body weight, as well as Mn accumulation, Nrf2 and Hsp70 expression across four brain regions; striatum, cortex, hippocampus and cerebellum in both sexes. Our results showed sex-specific changes in body-weight, specifically in males but not in females. Additionally, we noted sex-dependent accumulation of Mn in the brain, as well as in expression levels of Nrf2 and Hsp70 proteins. These findings revealed sex-dependent susceptibility to Mn-induced neurotoxicity corresponding to differential Mn accumulation, and expression of Hsp70 and Nrf2 across several brain regions. KW - brain KW - female KW - male KW - manganese KW - oxidative stress Y1 - 2022 U6 - https://doi.org/10.1002/tox.23583 SN - 1520-4081 SN - 1522-7278 VL - 37 IS - 9 SP - 2167 EP - 2177 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Varão Moura, Alexandre A1 - Aparecido Rosini Silva, Alex A1 - Domingos Santo da Silva, José A1 - Aleixo Leal Pedroza, Lucas A1 - Bornhorst, Julia A1 - Stiboller, Michael A1 - Schwerdtle, Tanja A1 - Gubert, Priscila T1 - Determination of ions in Caenorhabditis elegans by ion chromatography JF - Journal of chromatography. B N2 - The Caenorhabditis elegans (C. elegans) is a model organism that has been increasingly used in health and environmental toxicity assessments. The quantification of such elements in vivo can assist in studies that seek to relate the exposure concentration to possible biological effects. Therefore, this study is the first to propose a method of quantitative analysis of 21 ions by ion chromatography (IC), which can be applied in different toxicity studies in C. elegans. The developed method was validated for 12 anionic species (fluoride, acetate, chloride, nitrite, bromide, nitrate, sulfate, oxalate, molybdate, dichromate, phosphate, and perchlorate), and 9 cationic species (lithium, sodium, ammonium, thallium, potassium, magnesium, manganese, calcium, and barium). The method did not present the presence of interfering species, with R2 varying between 0.9991 and 0.9999, with a linear range from 1 to 100 mu g L-1. Limits of detection (LOD) and limits of quantification (LOQ) values ranged from 0.2319 mu g L-1 to 1.7160 mu g L-1 and 0.7028 mu g L-1 to 5.1999 mu g L-1, respectively. The intraday and interday precision tests showed an Relative Standard Deviation (RSD) below 10.0 % and recovery ranging from 71.0 % to 118.0 % with a maximum RSD of 5.5 %. The method was applied to real samples of C. elegans treated with 200 uM of thallium acetate solution, determining the uptake and bioaccumulated Tl+ content during acute exposure. KW - ion chromatography KW - C. elegans KW - method development KW - method validation KW - ion quantification Y1 - 2022 U6 - https://doi.org/10.1016/j.jchromb.2022.123312 SN - 1570-0232 SN - 1873-376X VL - 1204 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Rausch, Ann-Kristin A1 - Brockmeyer, Robert A1 - Schwerdtle, Tanja T1 - Development and validation of a liquid chromatography tandem mass spectrometry multi-method for the determination of 41 free and modified mycotoxins in beer JF - Food chemistry N2 - A fast high performance liquid chromatography tandem mass spectrometry multi-method based on an ACN-precipitation extraction was developed for the analysis of 41 (modified) mycotoxins in beer. Validation according to the performance criteria defined by the European Commission (EC) in Commission Decision no. 657/2002 revealed good linearity (R2 > 0.99), repeatability (RSDr < 15%), reproducibility (RSDR < 15%), and recovery (79–100%). Limits of quantification ranging from 0.04 to 75 µg/L were obtained. Matrix effects varied from −67 to +319% and were compensated for using standard addition. In total, 87 beer samples, produced worldwide, were analyzed for the presence of mycotoxins with a focus on modified mycotoxins, whereof 76% of the samples were contaminated with at least one mycotoxin. The most prevalent mycotoxins were deoxynivalenol-3-glucoside (63%), HT-2 toxin (15%), and tenuazonic acid (13%). Exposure estimates of deoxynivalenol and its metabolites for German beer revealed no significant contribution to intake of deoxynivalenol. KW - Multi-mycotoxin analysis KW - Modified mycotoxins KW - LC–MS/MS KW - Beer KW - Validation Y1 - 2020 U6 - https://doi.org/10.1016/j.foodchem.2020.127801 SN - 1873-7072 SN - 0308-8146 VL - 338 PB - Elsevier CY - New York, NY ER - TY - JOUR A1 - Rausch, Ann-Kristin A1 - Brockmeyer, Robert A1 - Schwerdtle, Tanja T1 - Development, validation, and application of a multi-method for the determination of mycotoxins, plant growth regulators, tropane alkaloids, and pesticides in cereals by two-dimensional liquid chromatography tandem mass spectrometry JF - Analytical & bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - Mycotoxins and pesticides regularly co-occur in agricultural products worldwide. Thus, humans can be exposed to both toxic contaminants and pesticides simultaneously, and multi-methods assessing the occurrence of various food contaminants and residues in a single method are necessary. A two-dimensional high performance liquid chromatography tandem mass spectrometry method for the analysis of 40 (modified) mycotoxins, two plant growth regulators, two tropane alkaloids, and 334 pesticides in cereals was developed. After an acetonitrile/water/formic acid (79:20:1, v/v/v) multi-analyte extraction procedure, extracts were injected into the two-dimensional setup, and an online clean-up was performed. The method was validated according to Commission Decision (EC) no. 657/2002 and document N° SANTE/12682/2019. Good linearity (R2 > 0.96), recovery data between 70-120%, repeatability and reproducibility values < 20%, and expanded measurement uncertainties < 50% were obtained for a wide range of analytes, including very polar substances like deoxynivalenol-3-glucoside and methamidophos. However, results for fumonisins, zearalenone-14,16-disulfate, acid-labile pesticides, and carbamates were unsatisfying. Limits of quantification meeting maximum (residue) limits were achieved for most analytes. Matrix effects varied highly (−85 to +1574%) and were mainly observed for analytes eluting in the first dimension and early-eluting analytes in the second dimension. The application of the method demonstrated the co-occurrence of different types of cereals with 28 toxins and pesticides. Overall, 86% of the samples showed positive findings with at least one mycotoxin, plant growth regulator, or pesticide. KW - 2D-LC-MS/MS KW - Multi-method KW - Mycotoxins KW - Modified mycotoxins KW - Pesticides KW - Cereals Y1 - 2021 U6 - https://doi.org/10.1007/s00216-021-03239-1 SN - 1618-2650 SN - 1618-2642 VL - 413 IS - 11 SP - 3041 EP - 3054 PB - Springer CY - Berlin ER - TY - JOUR A1 - Hackethal, Christin A1 - Kopp, Johannes Florian A1 - Sarvan, Irmela A1 - Schwerdtle, Tanja A1 - Lindtner, Oliver T1 - Total arsenic and water-soluble arsenic species in foods of the first German total diet study (BfR MEAL Study) JF - Food chemistry N2 - Arsenic can occur in foods as inorganic and organic forms. Inorganic arsenic is more toxic than most watersoluble organic arsenic compounds such as arsenobetaine, which is presumed to be harmless for humans. Within the first German total diet study, total arsenic, inorganic arsenic, arsenobetaine, dimethylarsinic acid and monomethylarsonic acid were analyzed in various foods. Highest levels of total arsenic were found in fish, fish products and seafood (mean: 1.43 mg kg(-1); n = 39; min-max: 0.01-6.15 mg kg(-1)), with arsenobetaine confirmed as the predominant arsenic species (1.233 mg kg 1; n = 39; min-max: 0.01-6.23 mg kg (1)). In contrast, inorganic arsenic was determined as prevalent arsenic species in terrestrial foods (0.02 mg kg (1); n = 38; min-max: 0-0.11 mg kg (1)). However, the toxicity of arsenic species varies and measurements are necessary to gain information about the composition and changes of arsenic species in foods due to household processing of foods. KW - Occurrence data KW - Food KW - Total arsenic KW - Arsenic speciation KW - Inductively KW - coupled plasma mass spectrometry Y1 - 2021 U6 - https://doi.org/10.1016/j.foodchem.2020.128913 SN - 0308-8146 SN - 1873-7072 VL - 346 PB - Elsevier CY - Amsterdam [u.a.] 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 - CHAP A1 - Wandt, Viktoria Klara Veronika A1 - Winkelbeiner, Nicola A1 - Loßow, Kristina A1 - Kopp, Johannes A1 - Simon, Luise A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Trace elements, ageing, and sex. Impact on genome stability BT - Abstracts of the 87th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) with contribution of the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e. V. (AGAH) T2 - Naunyn-Schmiedeberg's archives of pharmacology Y1 - 2021 U6 - https://doi.org/10.1007/s00210-021-02066-6 SN - 0028-1298 SN - 1432-1912 VL - 394 IS - Suppl. 1 SP - S13 EP - S13 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Pan, Yuanwei A1 - Ma, Xuehua A1 - Liu, Chuang A1 - Xing, Jie A1 - Zhou, Suqiong A1 - Parshad, Badri A1 - Schwerdtle, Tanja A1 - Li, Wenzhong A1 - Wu, Aiguo A1 - Haag, Rainer T1 - Retinoic acid-loaded dendritic polyglycerol-conjugated gold nanostars for targeted photothermal therapy in breast cancer stem cells JF - ACS nano N2 - The existence of cancer stem cells (CSCs) poses a major obstacle for the success of current cancer therapies, especially the fact that non-CSCs can spontaneously turn into CSCs, which lead to the failure of the treatment and tumor relapse. Therefore, it is very important to develop effective strategies for the eradication of the CSCs. In this work, we have developed a CSCs-specific targeted, retinoic acid (RA)-loaded gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatform for the efficient eradication of CSCs. The nanocomposites possess good biocompatibility and exhibit effective CSCs-specific multivalent targeted capability due to hyaluronic acid (HA) decorated on the multiple attachment sites of the bioinert dendritic polyglycerol (dPG). With the help of CSCs differentiation induced by RA, the self-renewal of breast CSCs and tumor growth were suppressed by the high therapeutic efficacy of photothermal therapy (PTT) in a synergistic inhibitory manner. Moreover, the stemness gene expression and CSC-driven tumorsphere formation were significantly diminished. In addition, the in vivo tumor growth and CSCs were also effectively eliminated, which indicated superior anticancer activity, effective CSCs suppression, and prevention of relapse. Taken together, we developed a CSCs-specific targeted, RA-loaded GNSs-dPG nanoplatform for the targeted eradication of CSCs and for preventing the relapse. KW - cancer stem cells KW - dendritic polyglycerol KW - gold nanostars KW - retinoic acid KW - photothermal therapy Y1 - 2021 U6 - https://doi.org/10.1021/acsnano.1c05452 SN - 1936-0851 SN - 1936-086X VL - 15 IS - 9 SP - 15069 EP - 15084 PB - American Chemical Society CY - Washington ER - TY - GEN A1 - Rausch, Ann-Kristin A1 - Brockmeyer, Robert A1 - Schwerdtle, Tanja T1 - Development, validation, and application of a multi-method for the determination of mycotoxins, plant growth regulators, tropane alkaloids, and pesticides in cereals by two-dimensional liquid chromatography tandem mass spectrometry T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Mycotoxins and pesticides regularly co-occur in agricultural products worldwide. Thus, humans can be exposed to both toxic contaminants and pesticides simultaneously, and multi-methods assessing the occurrence of various food contaminants and residues in a single method are necessary. A two-dimensional high performance liquid chromatography tandem mass spectrometry method for the analysis of 40 (modified) mycotoxins, two plant growth regulators, two tropane alkaloids, and 334 pesticides in cereals was developed. After an acetonitrile/water/formic acid (79:20:1, v/v/v) multi-analyte extraction procedure, extracts were injected into the two-dimensional setup, and an online clean-up was performed. The method was validated according to Commission Decision (EC) no. 657/2002 and document N° SANTE/12682/2019. Good linearity (R2 > 0.96), recovery data between 70-120%, repeatability and reproducibility values < 20%, and expanded measurement uncertainties < 50% were obtained for a wide range of analytes, including very polar substances like deoxynivalenol-3-glucoside and methamidophos. However, results for fumonisins, zearalenone-14,16-disulfate, acid-labile pesticides, and carbamates were unsatisfying. Limits of quantification meeting maximum (residue) limits were achieved for most analytes. Matrix effects varied highly (−85 to +1574%) and were mainly observed for analytes eluting in the first dimension and early-eluting analytes in the second dimension. The application of the method demonstrated the co-occurrence of different types of cereals with 28 toxins and pesticides. Overall, 86% of the samples showed positive findings with at least one mycotoxin, plant growth regulator, or pesticide. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1365 KW - 2D-LC-MS/MS KW - Multi-method KW - Mycotoxins KW - Modified mycotoxins KW - Pesticides KW - Cereals Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-514795 SN - 1866-8372 IS - 143 ER - 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 - GEN A1 - Nicolai, Merle Marie A1 - Weishaupt, Ann-Kathrin A1 - Baesler, Jessica A1 - Brinkmann, Vanessa A1 - Wellenberg, Anna A1 - Winkelbeiner, Nicola Lisa A1 - Gremme, Anna A1 - Aschner, Michael A1 - Fritz, Gerhard A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Effects of manganese on genomic integrity in the multicellular model organism Caenorhabditis elegans T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1173 KW - manganese KW - oxidative stress KW - DNA repair KW - DNA damage response KW - Caenorhabditis elegans Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-523275 SN - 1866-8372 IS - 1173 ER - TY - GEN A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1364 KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-514995 SN - 1866-8372 IS - 8 ER - TY - JOUR A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis JF - Molecular Nutrition and Food Research N2 - Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - https://doi.org/10.1002/mnfr.202001176 SN - 1613-4133 SN - 1613-4125 VL - 65 IS - 8 SP - 1 EP - 11 PB - Wiley-VCH GmbH CY - Weinheim ER - TY - JOUR A1 - Nicolai, Merle Marie A1 - Weishaupt, Ann-Kathrin A1 - Baesler, Jessica A1 - Brinkmann, Vanessa A1 - Wellenberg, Anna A1 - Winkelbeiner, Nicola Lisa A1 - Gremme, Anna A1 - Aschner, Michael A1 - Fritz, Gerhard A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Effects of manganese on genomic integrity in the multicellular model organism Caenorhabditis elegans JF - International Journal of Molecular Sciences N2 - Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms. KW - manganese KW - oxidative stress KW - DNA repair KW - DNA damage response KW - Caenorhabditis elegans Y1 - 2021 U6 - https://doi.org/10.3390/ijms222010905 SN - 1422-0067 VL - 22 IS - 20 PB - MDPI CY - Basel ER - TY - JOUR A1 - Kuhn, Eugênia Carla A1 - Tavares Jacques, Maurício A1 - Teixeira, Daniela A1 - Meyer, Sören A1 - Gralha, Thiago A1 - Roehrs, Rafael A1 - Camargo, Sandro A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia A1 - Ávila, Daiana Silva T1 - Ecotoxicological assessment of Uruguay River and affluents pre- and biomonitoring JF - Environmental science and pollution research : ESPR N2 - Uruguay River is the most important river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety. KW - Heavy metals KW - Pesticides KW - Contamination KW - Arsenic KW - Environmental KW - pollution KW - Uruguay River Y1 - 2021 U6 - https://doi.org/10.1007/s11356-020-11986-4 SN - 0944-1344 SN - 1614-7499 VL - 28 IS - 17 SP - 21730 EP - 21741 PB - Springer CY - Berlin ; Heidelberg ER - TY - CHAP A1 - Michaelis, Vivien A1 - Aengenheister, Leonie A1 - Schwerdtle, Tanja A1 - Buerki-Thurnherr, Tina A1 - Bornhorst, Julia T1 - Manganese translocation across an in vitro model of human villous trophoblast T2 - Placenta Y1 - 2021 U6 - https://doi.org/10.1016/j.placenta.2021.07.205 SN - 0143-4004 SN - 1532-3102 VL - 112 SP - E63 EP - E64 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Zhou, Suqiong A1 - Pan, Yuanwei A1 - Zhang, Jianguang A1 - Li, Yan A1 - Neumann, Falko A1 - Schwerdtle, Tanja A1 - Li, Wenzhong A1 - Haag, Rainer T1 - Dendritic polyglycerol-conjugated gold nanostars with different densities of functional groups to regulate osteogenesis in human mesenchymal stem cells JF - Nanoscale N2 - Nanomaterials play an important role in mimicking the biochemical and biophysical cues of the extracellular matrix in human mesenchymal stem cells (MSCs). Increasing studies have demonstrated the crucial impact of functional groups on MSCs, while limited research is available on how the functional group's density on nanoparticles regulates MSC behavior. Herein, the effects of dendritic polyglycerol (dPG)-conjugated gold nanostars (GNSs) with different densities of functional groups on the osteogenesis of MSCs are systematically investigated. dPG@GNS nanocomposites have good biocompatibility and the uptake by MSCs is in a functional group density-dependent manner. The osteogenic differentiation of MSCs is promoted by all dPG@GNS nanocomposites, in terms of alkaline phosphatase activity, calcium deposition, and expression of osteogenic protein and genes. Interestingly, the dPGOH@GNSs exhibit a slight upregulation in the expression of osteogenic markers, while the different charged densities of sulfate and amino groups show more efficacy in the promotion of osteogenesis. Meanwhile, the sulfated nanostars dPGS20@GNSs show the highest enhancement. Furthermore, various dPG@GNS nanocomposites exerted their effects by regulating the activation of Yes-associated protein (YAP) to affect osteogenic differentiation. These results indicate that dPG@GNS nanocomposites have functional group density-dependent influence on the osteogenesis of MSCs, which may provide a new insight into regulating stem cell fate. Y1 - 2020 U6 - https://doi.org/10.1039/d0nr06570f SN - 2040-3364 SN - 2040-3372 VL - 12 IS - 47 SP - 24006 EP - 24019 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Müller, Sandra A1 - Dawczynski, Christine A1 - Wiest, Johanna A1 - Lorkowski, Stefan A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Functional Biomarkers for the Selenium Status in a Human Nutritional Intervention Study T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 878 KW - Se KW - selenoprotein P KW - GPx activity KW - cardiovascular disease KW - status markers Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-460115 SN - 1866-8372 IS - 878 ER - TY - GEN A1 - Witt, Barbara A1 - Schaumlöffel, Dirk A1 - Schaumlöffel, Dirk A1 - Schwerdtle, Tanja T1 - Subcellular Localization of Copper BT - Cellular Bioimaging with Focus on Neurological Disorders T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 862 KW - copper KW - cellular bioimaging KW - neurodegenerative diseases KW - copper-related disorders KW - SIMS techniques KW - TEM KW - S-XRF Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-459544 SN - 1866-8372 IS - 862 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 - Kotthoff, Lisa A1 - O'Callaghan, Sarah-Louise A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry JF - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown. KW - veterinary drug KW - moxidectin KW - transformation products KW - electrochemistry KW - photochemistry KW - LC KW - HRMS Y1 - 2020 U6 - https://doi.org/10.1007/s00216-020-02572-1 SN - 1618-2642 SN - 1618-2650 VL - 412 IS - 13 SP - 3141 EP - 3152 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Rausch, Ann-Kristin A1 - Brockmeyer, Robert A1 - Schwerdtle, Tanja T1 - Development and Validation of a QuEChERS-Based Liquid Chromatography Tandem Mass Spectrometry Multi-Method for the Determination of 38 Native and Modified Mycotoxins in Cereals JF - Journal of Agricultural and Food Chemistry N2 - Here, a reliable and sensitive method for the determination of 38 (modified) mycotoxins was developed. Using a QuEChERS-based extraction method [acetonitrile/water/formic acid (75:20:5, v/v/v)], followed by two runs of high performance liquid chromatography tandem mass spectrometry with different conditions, relevant mycotoxins in cereals were analyzed. The method was validated according to the performance criteria defined by the European Commission (EC) in Commission Decision no. 657/2002. Limits of quantification ranged from 0.05 to 150 μg/kg. Good linearity (R2 > 0.99), recovery (61–120%), repeatability (RSDr < 15%), and reproducibility (RSDR < 20%) were obtained for most mycotoxins. However, validation results for Alternaria toxins and fumonisins were unsatisfying. Matrix effects (−69 to +59%) were compensated for using standard addition. Application on reference materials gave correct results while analysis of samples from local retailers revealed contamination, especially with deoxynivalenol, deoxynivalenol-3-glucoside, fumonisins, and zearalenone, in concentrations up to 369, 58, 1002, and 21 μg/kg, respectively. KW - multi-mycotoxin analysis KW - modified mycotoxins KW - QuEChERS KW - LC−MS/MS KW - cereals KW - validation Y1 - 2020 U6 - https://doi.org/10.1021/acs.jafc.9b07491 SN - 0021-8561 VL - 68 IS - 16 SP - 4657 EP - 4669 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Dünkelberg, Sophie A1 - Maywald, Martina A1 - Schmitt, Anne Kristina A1 - Schwerdtle, Tanja A1 - Meyer, Sören A1 - Rink, Lothar T1 - The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells JF - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology N2 - Scope: Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium. Methods and Results: Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium. Conclusion: This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways. KW - Foxp3 KW - regulatory T cells KW - sodium KW - T helper 17 cells KW - zinc Y1 - 2020 U6 - https://doi.org/10.1002/mnfr.201900245 SN - 1613-4133 VL - 64 IS - 2 PB - Wiley-VCH CY - Weinheim 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 - Müller, Anke Katharina A1 - Helms, Ute A1 - Rohrer, Carsten A1 - Möhler, Monika A1 - Hellwig, Frank A1 - Glei, Michael A1 - Schwerdtle, Tanja A1 - Lorkowski, Stefan A1 - Dawczynski, Christine T1 - Nutrient composition of different hazelnut cultivars grown in Germany JF - Foods N2 - Hazelnuts are rarely cultivated in Germany, although they are a valuable source for macro- and micronutrients and can thus contribute to a healthy diet. Near the present, 15 varieties were cultivated in Thuringia, Germany, as a pilot study for further research. The aim of our study was to evaluate the micro- and macronutrient composition of representative, randomly mixed samples of the 15 different hazelnut cultivars. Protein, fat, and fiber contents were determined using established methods. Fatty acids, tocopherols, minerals, trace elements, and ultra-trace elements were analyzed using gas chromatography, high-performance liquid chromatography, and inductively coupled plasma triple quadrupole mass-spectrometry, respectively. We found that the different hazelnut varieties contained valuable amounts of fat, protein, dietary fiber, minerals, trace elements, and alpha-tocopherol, however, in different quantities. The variations in nutrient composition were independent of growth conditions, which were identical for all hazelnut varieties. Therefore, each hazelnut cultivar has its specific nutrient profile. KW - Corylus avellana L. KW - nutrient composition KW - hazelnut cultivars KW - minerals KW - tocopherols Y1 - 2020 U6 - https://doi.org/10.3390/foods9111596 SN - 2304-8158 VL - 9 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Witt, Barbara A1 - Schaumlöffel, Dirk A1 - Schwerdtle, Tanja T1 - Subcellular Localization of Copper BT - Cellular Bioimaging with Focus on Neurological Disorders JF - International Journal of Molecular Sciences N2 - As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences. KW - copper KW - cellular bioimaging KW - neurodegenerative diseases KW - copper-related disorders KW - SIMS techniques KW - TEM KW - S-XRF Y1 - 2020 U6 - https://doi.org/10.3390/ijms21072341 SN - 1422-0067 VL - 21 IS - 7 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Müller, Sandra A1 - Dawczynski, Christine A1 - Wiest, Johanna A1 - Lorkowski, Stefan A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Functional Biomarkers for the Selenium Status in a Human Nutritional Intervention Study JF - Nutrients N2 - Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se KW - Se KW - selenoprotein P KW - GPx activity KW - cardiovascular disease KW - status markers Y1 - 2020 U6 - https://doi.org/10.3390/nu12030676 SN - 2072-6643 VL - 12 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Volk, Christin A1 - Brandsch, Corinna A1 - Schlegelmilch, Ulf A1 - Wensch-Dorendorf, Monika A1 - Hirche, Frank A1 - Simm, Andreas A1 - Gargum, Osama A1 - Wiacek, Claudia A1 - Braun, Peggy G. A1 - Kopp, Johannes F. A1 - Schwerdtle, Tanja A1 - Treede, Hendrik A1 - Stangl, Gabriele I. T1 - Postprandial metabolic response to rapeseed protein in healthy subjects JF - Nutrients N2 - Plant proteins have become increasingly important for ecological reasons. Rapeseed is a novel source of plant proteins with high biological value, but its metabolic impact in humans is largely unknown. A randomized, controlled intervention study including 20 healthy subjects was conducted in a crossover design. All participants received a test meal without additional protein or with 28 g of rapeseed protein isolate or soy protein isolate (control). Venous blood samples were collected over a 360-min period to analyze metabolites; satiety was assessed using a visual analog scale. Postprandial levels of lipids, urea, and amino acids increased following the intake of both protein isolates. The postprandial insulin response was lower after consumption of the rapeseed protein than after intake of the soy protein (p< 0.05), whereas the postmeal responses of glucose, lipids, interleukin-6, minerals, and urea were comparable between the two protein isolates. Interestingly, the rapeseed protein exerted stronger effects on postprandial satiety than the soy protein (p< 0.05). The postmeal metabolism following rapeseed protein intake is comparable with that of soy protein. The favorable effect of rapeseed protein on postprandial insulin and satiety makes it a valuable plant protein for human nutrition. KW - rapeseed protein KW - soy protein KW - postprandial study KW - metabolic response KW - healthy subjects Y1 - 2020 U6 - https://doi.org/10.3390/nu12082270 SN - 2072-6643 VL - 12 IS - 8 PB - MDPI CY - Basel ER - 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 - Nicolai, Merle Marie A1 - Baesler, Jessica A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Consequences of manganese overload in C. elegans BT - oxidative stress and DNA damage JF - Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie Y1 - 2020 U6 - https://doi.org/10.1007/s00210-020-01828-y SN - 0028-1298 SN - 1432-1912 VL - 393 IS - SUPPL 1 SP - 9 EP - 9 PB - Springer CY - New York 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 - Alker, Wiebke A1 - Schwerdtle, Tanja A1 - Schomburg, Lutz A1 - Haase, Hajo T1 - A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum JF - International journal of molecular sciences N2 - Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status. KW - zinc KW - free zinc KW - serum KW - biomarker KW - fluorescent probe KW - Zinypr-1 Y1 - 2019 U6 - https://doi.org/10.3390/ijms20164006 SN - 1661-6596 SN - 1422-0067 VL - 20 IS - 16 PB - MDPI CY - Basel ER - TY - GEN A1 - Schwarz, Maria A1 - Lossow, Kristina A1 - Kopp, Johannes F. A1 - Schwerdtle, Tanja A1 - Kipp, Anna Patricia T1 - Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1081 KW - Nrf2 KW - selenium KW - iron KW - copper KW - zinc KW - homeostasis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-472873 SN - 1866-8372 IS - 1081 ER - TY - GEN A1 - Alker, Wiebke A1 - Schwerdtle, Tanja A1 - Schomburg, Lutz A1 - Haase, Hajo T1 - A Zinpyr-1-based fluorimetric microassay for free zinc in human serum T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1086 KW - zinc KW - free zinc KW - serum KW - biomarker KW - fluorescent probe KW - Zinypr-1 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-472833 SN - 1866-8372 IS - 1086 ER - TY - JOUR A1 - Kopp, Johannes Florian A1 - Müller, Sandra Marie A1 - Pohl, Gabriele A1 - Lossow, Kristina A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS JF - Journal of trace elements in medicine and biology N2 - In order to assess the individual trace element status of humans for either medical or scientific purposes, amongst others, blood serum levels are determined. Furthermore, animal models are used to study interactions of trace elements. Most published methods require larger amounts (500-1000 mu L) of serum to achieve a reliable determination of multiple trace elements. However, oftentimes, these amounts of serum cannot be dedicated to a single analysis and the amount available for TE-determination is much lower. Therefore, a published ICP-MS/MS method for trace element determination in serum was miniaturized, optimized and validated for the measurement of Mn, Fe, Cu Zn, I and Se in as little as 50 mu L of human and murine serum and is presented in this work. For validation, recoveries of multiple LOTs and levels from commercially available human reference serum samples were determined, infra- and inter-day variations were assessed and limits of detection and quantification determined. It is shown, that the method is capable of giving accurate and reproducible results for all six elements within the relevant concentration ranges for samples from humans living in central Europe as well as from laboratory mice. As a highlight, the achieved limits of detection and quantification for Mn were found to be at 0.02 mu g/L serum and 0.05 mu g/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine. Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.04.015 SN - 0946-672X VL - 54 SP - 221 EP - 225 PB - Elsevier CY - München ER - TY - JOUR A1 - Basaran, Nursen A1 - Duydu, Yalcin A1 - Ustundag, Aylin A1 - Taner, Gokce A1 - Aydin, Sevtap A1 - Anlar, Hatice Gul A1 - Yalcin, Can Özgür A1 - Bacanli, Merve A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Schwerdtle, Tanja A1 - Werner, Matthias A1 - Meyer, Sören A1 - Bolt, Hermann M. T1 - Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions JF - Mutation Research/Genetic Toxicology and Environmental Mutagenesis N2 - Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions. KW - Boric acid KW - Boron exposure KW - DNA damage KW - Comet assay Y1 - 2019 U6 - https://doi.org/10.1016/j.mrgentox.2018.12.013 SN - 1383-5718 SN - 1879-3592 VL - 843 SP - 33 EP - 39 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Li, Mingjun A1 - Schlaich, Christoph A1 - Kulka, Michael Willem A1 - Donskyi, Ievgen S. A1 - Schwerdtle, Tanja A1 - Unger, Wolfgang E. S. A1 - Haag, Rainer T1 - Mussel-inspired coatings with tunable wettability, for enhanced antibacterial efficiency and reduced bacterial adhesion JF - Journal of materials chemistry : B, Materials for biology and medicine N2 - Over the last few decades, there has been a tremendous increase in research on antibacterial surface coatings as an alternative strategy against bacterial infections. Although there are several examples of effective strategies to prevent bacterial adhesion, the effect of the wetting properties on the coating was rarely considered as a crucial factor. Here we report an in-depth study on the effect of extreme wettability on the antibacterial efficiency of a silver nanoparticles ( AgNPs)-based coating. By controlling surface polymerization of mussel-inspired dendritic polyglycerol ( MI-dPG) and post-functionalization, surfaces with wetting properties ranging from superhydrophilic to superhydrophobic were fabricated. Subsequently, AgNPs were embedded into the coatings by applying in situ reduction using the free catechols-moieties present in the MI-dPG coating. The resulting polymer coatings exhibited excellent antibacterial ability against planktonic Escherichia coli ( E. coli) DH5a and Staphylococcus aureus ( S. aureus) SH1000. The antibacterial efficiency of the coatings was analyzed by using inductively coupled plasma mass spectrometry ( ICP-MS) and bacterial viability tests. Furthermore, the antifouling properties of the coatings in relation to the antibacterial properties were evaluated. Y1 - 2019 U6 - https://doi.org/10.1039/c9tb00534j SN - 2050-750X SN - 2050-7518 VL - 7 IS - 21 SP - 3438 EP - 3445 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Duydu, Yalcin A1 - Basaran, Nursen A1 - Yalcin, Can Özgür A1 - Ustundag, Aylin A1 - Aydin, Sevtap A1 - Anlar, Hatice Gul A1 - Bacanli, Merve A1 - Aydos, Kaan A1 - Atabekoglu, Cem Somer A1 - Golka, Klaus A1 - Ickstadt, Katja A1 - Schwerdtle, Tanja A1 - Werner, Matthias A1 - Bolt, Hermann M. T1 - Boron-exposed male workers in Turkey BT - no change in sperm Y:X chromosome ratio and in offspring's sex ratio JF - Archives of toxicology : official journal of EUROTOX N2 - Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. In the present study, 304 male workers in Bandirma and Bigadic (Turkey) with different degrees of occupational and environmental exposure to boron were investigated. Boron was quantified in blood, urine and semen, and the persons were allocated to exposure groups along B blood levels. In the highest ("extreme") exposure group (n = 69), calculated mean daily boron exposures, semen boron and blood boron concentrations were 44.91 +/- 18.32 mg B/day, 1643.23 +/- 965.44 ng B/g semen and 553.83 +/- 149.52 ng B/g blood, respectively. Overall, an association between boron exposure and Y:X sperm ratios in semen was not statistically significant (p > 0.05). Also, the mean Y:X sperm ratios in semen samples of workers allocated to the different exposure groups were statistically not different in pairwise comparisons (p > 0.05). Additionally, a boron-associated shift in sex ratio at birth towards female offspring was not visible. In essence, the present results do not support an association between boron exposure and decreased Y:X sperm ratio in males, even under extreme boron exposure conditions. KW - Paternal exposure KW - Boron exposure KW - Y:X chromosome ratio KW - Sex ratio at birth Y1 - 2019 U6 - https://doi.org/10.1007/s00204-019-02391-z SN - 0340-5761 SN - 1432-0738 VL - 93 IS - 3 SP - 743 EP - 751 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Kroepfl, Nina A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja A1 - Kuehnelt, Doris T1 - Selenoneine and ergothioneine in human blood cells determined simultaneously by HPLC/ICP-QQQ-MS JF - Journal of Analytical Atomic Spectrometry N2 - The possible relevance to human health of selenoneine and its sulfur-analogue ergothioneine has generated interest in their quantitative determination in biological samples. To gain more insight into the similarities and differences of these two species, a method for their simultaneous quantitative determination in human blood cells using reversed-phase high performance liquid chromatography (RP-HPLC) coupled to inductively coupled plasma triple quadrupole mass spectrometry (ICP-QQQ-MS) is presented. Spectral interferences hampering the determination of sulfur and selenium by ICPMS are overcome by introducing oxygen to the reaction cell. To access selenoneine and ergothioneine in the complex blood matrix, lysis of the cells with cold water followed by cut-off filtration (3000 Da) is performed. Recoveries based on blood cells spiked with selenoneine and ergothioneine were between 80% and 85%. The standard deviation of the method was around 0.10 mg S per L for ergothioneine (corresponding to relative standard deviations (RSD) between 10-1% for ergothioneine concentrations of 1-10 mg S per L) and 0.25 g Se per L for selenoneine (RSDs of 25-2% for concentrations of 1-10 g Se per L). The method was applied to blood cell samples from three volunteers which showed selenoneine and ergothioneine concentrations in the range of 3.25 to 7.35 g Se per L and 0.86 to 6.44 mg S per L, respectively. The method is expected to be of wide use in future studies investigating the dietary uptake of selenoneine and ergothioneine and their relevance in human health. Y1 - 2018 U6 - https://doi.org/10.1039/c8ja00276b SN - 0267-9477 SN - 1364-5544 VL - 34 IS - 1 SP - 127 EP - 134 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Başaran, Nurşen A1 - Duydu, Yalçın A1 - Üstündağ, Aylin A1 - Taner, Gökçe A1 - Aydin Dilsiz, Sevtap A1 - Anlar, Hatice Gül A1 - Yalçin, Can Özgür A1 - Bacanli, Merve A1 - Golka, Klaus A1 - Schwerdtle, Tanja A1 - Bolt, Hermann M. T1 - Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females DNA damage in lymphocytes and buccal cells of boron exposed females JF - Journal of trace elements in medicine and biology N2 - Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boronpoor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions. KW - Boric acid KW - Boron exposure KW - DNA damage Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.03.004 SN - 0946-672X VL - 53 SP - 150 EP - 153 PB - Elsevier B.V. CY - München ER - TY - JOUR A1 - Schwarz, Maria A1 - Lossow, Kristina A1 - Kopp, Johannes Florian A1 - Schwerdtle, Tanja A1 - Kipp, Anna Patricia T1 - Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper JF - Nutrients N2 - Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice. KW - Nrf2 KW - selenium KW - iron KW - copper KW - zinc KW - homeostasis Y1 - 2019 U6 - https://doi.org/10.3390/nu11092112 SN - 2072-6643 VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - GEN A1 - Kotthoff, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid+ chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1340 KW - transformation products KW - monensin KW - veterinary drugs KW - electrochemistry KW - hydrolysis KW - LC/HRMS Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473262 SN - 1866-8372 IS - 1340 ER - TY - JOUR A1 - Kotthoff, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis JF - Molecules N2 - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation. KW - transformation products KW - monensin KW - veterinary drugs KW - electrochemistry KW - hydrolysis KW - LC/HRMS Y1 - 2019 U6 - https://doi.org/10.3390/molecules24152732 SN - 1420-3049 VL - 24 IS - 15 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schutkowski, Alexandra A1 - König, Bettina A1 - Kluge, Holger A1 - Hirche, Frank A1 - Henze, Andrea A1 - Schwerdtle, Tanja A1 - Lorkowski, Stefan A1 - Dawczynski, Christine A1 - Gabel, Alexander A1 - Grosse, Ivo A1 - Stangl, Gabriele I. T1 - Metabolic footprint and intestinal microbial changes in response to dietary proteins in a pig model JF - The journal of nutritional biochemistry N2 - Epidemiological studies revealed that dietary proteins can contribute to the modulation of the cardiovascular disease risk. Still, direct effects of dietary proteins on serum metabolites and other health-modulating factors have not been fully explored. Here, we compared the effects of dietary lupin protein with the effects of beef protein and casein on the serum metabolite profile, cardiovascular risk markers and the fecal microbiome. Pigs were fed diets containing 15% of the respective proteins for 4 weeks. A classification analysis of the serum metabolites revealed six biomarker sets of two metabolites each that discriminated between the intake of lupin protein, lean beef or casein. These biomarker sets included 1- and 3-methylhistidine, betaine, carnitine, homoarginine and methionine. The study revealed differences in the serum levels of the metabolites 1- and 3- methylhistidine, homoarginine, methionine and homocysteine, which are involved in the one-carbon cycle. However, these changes were not associated with differences in the methylation capacity or the histone methylation pattern. With the exception of serum homocysteine and homoarginine levels, other cardiovascular risk markers, such as the homeostatic model assessment index, trimethylamine-N-oxide and lipids, were not influenced by the dietary protein source. However, the composition of the fecal microorganisms was markedly changed by the dietary protein source. Lupin-protein-fed pigs exhibited more species from the phyla Bacteroidetes and Firmicutes than the other two groups. In conclusion, different dietary protein sources induce distinct serum metabolic fingerprints, have an impact on the cardiovascular risk and modulate the composition of the fecal microbiome. (C) 2019 Elsevier Inc. All rights reserved. KW - Lupin KW - Beef KW - Casein KW - Pig KW - Biomarker KW - Microbiome Y1 - 2019 U6 - https://doi.org/10.1016/j.jnutbio.2019.02.004 SN - 0955-2863 SN - 1873-4847 VL - 67 SP - 149 EP - 160 PB - Elsevier CY - New York ER - TY - JOUR A1 - Peres, Tanara V. A1 - Horning, Kyle J. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Bowman, Aaron B. A1 - Aschner, Michael T1 - Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo JF - Biological Trace Element Research N2 - Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric disturbances and may arise from an impaired or not fully developed excretion system, transporter malfunction and/or exposure to excessive levels of Mn. Therefore, deciphering processes regulating neuronal Mn homeostasis is essential to understand the mechanisms of Mn neurotoxicity. In the present study, we selected two small molecules (with opposing effects on Mn transport) from a previous high throughput screen of 40,167 to test their effects on Mn toxicity parameters in vivo using Caenorhabditis elegans. We pre-exposed worms to VU0063088 and VU0026921 for 30min followed by co-exposure for 1h with Mn and evaluated Mn accumulation, dopaminergic (DAergic) degeneration and worm survival. Control worms were exposed to vehicle (DMSO) and saline only. In pdat-1::GFP worms, with GFP labeled DAergic neurons, we observed a decrease of Mn-induced DAergic degeneration in the presence of both small molecules. This effect was also observed in an smf-2 knockout strain. SMF-2 is a regulator of Mn transport in the worms and this strain accumulates higher Mn levels. We did not observe improved survival in the presence of small molecules. Our results suggest that both VU0063088 and VU0026921 may modulate Mn levels in the worms through a mechanism that does not require SMF-2 and induce protection against Mn neurotoxicity. KW - Small molecules KW - Manganese KW - Neurotoxicity KW - C. elegans KW - Dopamine Y1 - 2018 U6 - https://doi.org/10.1007/s12011-018-1531-7 SN - 0163-4984 SN - 1559-0720 VL - 188 IS - 1 SP - 127 EP - 134 PB - Human press inc. CY - Totowa ER -