TY  - THES
A1  - Meyer, Sören
T1  - Toxicity and toxicokinetics of arsenolipids and their metabolites
Y1  - 2015
ER  - 
TY  - JOUR
A1  - Kumar, Kevin K.
A1  - Goodwin, Cody R.
A1  - Uhouse, Michael A.
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Aschner, Michael A.
A1  - McLean, John A.
A1  - Bowman, Aaron B.
T1  - Untargeted metabolic profiling identifies interactions between
JF  - Metallomics : integrated biometal science
Y1  - 2015
U6  - https://doi.org/10.1039/c4mt00223g
SN  - 1756-5901
SN  - 1756-591X
VL  - 7
IS  - 2
SP  - 363
EP  - 370
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Chen, Pan
A1  - DeWitt, Margaret R.
A1  - Bornhorst, Julia
A1  - Soares, Felix A.
A1  - Mukhopadhyay, Somshuvra
A1  - Bowman, Aaron B.
A1  - Aschner, Michael A.
T1  - Age- and manganese-dependent modulation of dopaminergic phenotypes in a
JF  - Metallomics : integrated biometal science
Y1  - 2015
U6  - https://doi.org/10.1039/c4mt00292j
SN  - 1756-5901
SN  - 1756-591X
VL  - 7
IS  - 2
SP  - 289
EP  - 298
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Dschietzig, Thomas Bernd
A1  - Krause-Relle, Katharina
A1  - Hennequin, Maud
A1  - von Websky, Karoline
A1  - Rahnenfuhrer, Jan
A1  - Ruppert, Jana
A1  - Groena, Hans Juergen
A1  - Armbruster, Franz Paul
A1  - Bathgate, Ross A. D.
A1  - Aschenbach, Joerg R.
A1  - Forssmann, Wolf-Georg
A1  - Hocher, Berthold
T1  - Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.
KW  - Diabetic nephropathy
KW  - Diabetic cardiomyopathy
KW  - Fibrosis
KW  - Inflammation
KW  - Relaxin
Y1  - 2015
U6  - https://doi.org/10.1159/000368484
SN  - 1420-4096
SN  - 1423-0143
VL  - 40
IS  - 1
SP  - 77
EP  - 88
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Chakraborty, Sudipta
A1  - Chen, Pan
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Bowman, Aaron B.
A1  - Aschner, Michael A.
T1  - Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C-elegans
JF  - Metallomics : integrated biometal science
Y1  - 2015
U6  - https://doi.org/10.1039/c5mt00052a
SN  - 1756-5901
SN  - 1756-591X
VL  - 7
IS  - 5
SP  - 847
EP  - 856
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Hasselhoff, Görge K.
T1  - Midrash Unbound. Transformations and Innovations
JF  - Zeitschrift für Religions- und Geistesgeschichte
Y1  - 2015
SN  - 0044-3441
VL  - 67
IS  - 2
SP  - 205
EP  - 206
PB  - Brill
CY  - Leiden
ER  - 
TY  - JOUR
A1  - Crone, Barbara
A1  - Aschner, Michael A.
A1  - Schwerdtle, Tanja
A1  - Karst, Uwe
A1  - Bornhorst, Julia
T1  - Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS
JF  - Metallomics : integrated biometal science
N2  - cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 mm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose) metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.
Y1  - 2015
U6  - https://doi.org/10.1039/c5mt00096c
SN  - 1756-5901
SN  - 1756-591X
VL  - 7
IS  - 7
SP  - 1189
EP  - 1195
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Raber, Georg
A1  - Ebert, Franziska
A1  - Leffers, L.
A1  - Mueller, Sandra Maria
A1  - Taleshi, M. S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites
JF  - Toxicology research
N2  - Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMA(V), DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at mu M concentrations. DMA(V) causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMA(V) in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.
Y1  - 2015
U6  - https://doi.org/10.1039/c5tx00122f
SN  - 2045-452X
SN  - 2045-4538
VL  - 4
IS  - 5
SP  - 1289
EP  - 1296
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Peng, Tao
A1  - Zhu, Ganghua
A1  - Dong, Yunpeng
A1  - Zeng, Junjie
A1  - Li, Wei
A1  - Guo, Weiwei
A1  - Chen, Yong
A1  - Duan, Maoli
A1  - Hocher, Berthold
A1  - Xie, Dinghua
T1  - BMP4: a possible key factor in differentiation of auditory neuron-like cells from bone-derived mesenchymal stromal cells
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: Previous studies have shown that BMP4 may play an important part in the development of auditory neurons (ANs), which are degenerated in sensorineural hearing loss. However, whether BMP4 can promote sensory fate specification from mesenchymal stromal cells (MSCs) is unknown so far.
 Methods: MSCs isolated from Sprague-Dawley (SD) rats were confirmed by expression of MSC markers using flow cytometry and adipogenesis/osteogenesis using differentiation assays. MSCs treated with a complex of neurotrophic factors (BMP4 group and non-BMP4 group) were induced into auditory neuron-like cells, then the differences between the two groups were analyzed in morphological observation, cell growth curve, qRT-PCR, and immunofluorescence.
 Results: Flow cytometric analysis showed that the isolated cells expressed typical MSC surface markers. After adipogenic and osteogenic induction, the cells were stained by oil red O and Alizarin Red. The neuronal induced cells were in the growth plateau and had special forms of neurons. In the presence of BMP4, the inner ear genes NF-M, Neurog1, GluR4, NeuroD, Calretinin, NeuN, Tau, and GATA3 were up-regulated in MSCs.
 Conclusions: MSCs have the capacity to differentiate into auditory neuron-like cells in vitro. As an effective inducer, BMP4 may play a key role in transdifferentiation.
KW  - differentiation
KW  - auditory neurons
KW  - BMP4
Y1  - 2015
U6  - https://doi.org/10.7754/Clin.Lab.2015.150217
SN  - 1433-6510
VL  - 61
IS  - 9
SP  - 1171
EP  - 1178
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Lohren, Hanna
A1  - Bornhorst, Julia
A1  - Galla, Hans-Joachim
A1  - Schwerdtle, Tanja
T1  - The blood-cerebrospinal fluid barrier - first evidence for an active transport of organic mercury compounds out of the brain
JF  - Metallomics : integrated biometal science
N2  - Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.
Y1  - 2015
U6  - https://doi.org/10.1039/c5mt00171d
SN  - 1756-5901
SN  - 1756-591X
VL  - 7
IS  - 10
SP  - 1420
EP  - 1430
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  -