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 - Baesler, Jessica A1 - Kopp, Johannes Florian A1 - Pohl, Gabriele A1 - Aschner, Michael A1 - Haase, Hajo A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Zn homeostasis in genetic models of Parkinson’s disease in Caenorhabditis elegans JF - Journal of Trace Elements in Medicine and Biology N2 - While the underlying mechanisms of Parkinson’s disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD. KW - Caenorhabditis elegans KW - Zinc KW - Zinc homeostasis KW - Parkinson disease KW - Labile zinc Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.05.005 VL - 55 SP - 44 EP - 49 PB - Elsevier CY - München 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 - Ruszkiewicz, Joanna A. A1 - de Macedo, Gabriel Teixeira A1 - Miranda-Vizuete, Antonio A1 - Bowman, Aaron B. A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Antunes Soares, Felix A. A1 - Aschner, Michael T1 - Sex-Specific response of caenorhabditis elegans to Methylmercury Toxicity JF - Neurotoxicity Research N2 - Methylmercury (MeHg), an abundant environmental pollutant, has long been known to adversely affect neurodevelopment in both animals and humans. Several reports from epidemiological studies, as well as experimental data indicate sex-specific susceptibility to this neurotoxicant; however, the molecular bases of this process are still not clear. In the present study, we used Caenorhabditis elegans (C. elegans), to investigate sex differences in response to MeHg toxicity during development. Worms at different developmental stage (L1, L4, and adult) were treated with MeHg for 1h. Lethality assays revealed that male worms exhibited significantly higher resistance to MeHg than hermaphrodites, when at L4 stage or adults. However, the number of worms with degenerated neurons was unaffected by MeHg, both in males and hermaphrodites. Lower susceptibility of males was not related to changes in mercury (Hg) accumulation, which was analogous for both wild-type (wt) and male-rich him-8 strain. Total glutathione (GSH) levels decreased upon MeHg in him-8, but not in wt. Moreover, the sex-dependent response of the cytoplasmic thioredoxin system was observedmales exhibited significantly higher expression of thioredoxin TRX-1, and thioredoxin reductase TRXR-1 expression was downregulated upon MeHg treatment only in hermaphrodites. These outcomes indicate that the redox status is an important contributor to sex-specific sensitivity to MeHg in C. elegans. KW - Methylmercury KW - Sex KW - Male KW - C KW - elegans KW - Antioxidant KW - Thioredoxin Y1 - 2019 U6 - https://doi.org/10.1007/s12640-018-9949-4 SN - 1029-8428 SN - 1476-3524 VL - 35 IS - 1 SP - 208 EP - 216 PB - Springer 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 - 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 - 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 - 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 - Rohn, Isabelle A1 - Raschke, Stefanie A1 - Aschner, Michael A1 - Tuck, Simon A1 - Kuehnelt, Doris A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Treatment of caenorhabditis elegans with small selenium species enhances antioxidant defense systems JF - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology N2 - ScopeSmall selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo. Methods and resultsIn the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data. ConclusionSe species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake. KW - antioxidant defense systems KW - caenorhabditis elegans KW - selenium KW - oxidative stress KW - selenoproteins Y1 - 2019 U6 - https://doi.org/10.1002/mnfr.201801304 SN - 1613-4125 SN - 1613-4133 VL - 63 IS - 9 PB - Wiley CY - Hoboken 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 -