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Archives of Toxicology

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https://www.readbyqxmd.com/read/28397090/tributyltin-in-male-mice-disrupts-glucose-homeostasis-as-well-as-recovery-after-exposure-mechanism-analysis
#1
Bingshui Li, Jiaojiao Guo, Zhihui Xi, Jing Xu, Zhenghong Zuo, Chonggang Wang
Organotin compounds such as tributyltin (TBT) and triphenyltin can induce diabetes and insulin resistance. However, the development of diabetes caused by organotins and its underlying mechanisms remain unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 μg/kg) once every 3 days for 45 days. Their body weights increased and reached a significant difference compared to the control, and the fasting blood glucose levels were significantly elevated. The fasting levels of serum insulin and adiponectin increased, while glucagon levels decreased in the animals treated with TBT...
April 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28393304/lanthanum-chloride-precipitation-based-toxicoproteomic-analysis-of-3-monochloropropane-1-2-diol-toxicity-in-rat-kidney-reveals-involvement-of-extracellular-signal-regulated-kinase-2
#2
Axel Oberemm, Monique Braun, Stefanie Sawada, Mario Pink, Falko Frenzel, Christel Rozycki, Christine Meckert, Elke Zabinsky, Albert Braeuning, Alfonso Lampen
The heat-induced food contaminant 3-monochloropropane-1,2-diol (3-MCPD) and its fatty acid esters exert nephrotoxicity in rodents. Previous studies including a non-targeted toxicoproteomics approach using samples from a 28-day oral toxicity study in rats with 10 mg/kg body weight (b.w.) of 3-MCPD, an equimolar dose of 53 mg/kg b.w. 3-MCPD dipalmitate and a lower dose of 13.3 mg/kg b.w. of 3-MCPD dipalmitate, revealed substance-induced alterations in metabolic pathways, especially for glycolysis and energy metabolism...
April 9, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28391356/rat-precision-cut-liver-slices-predict-drug-induced-cholestatic-injury
#3
Viktoriia Starokozhko, Rick Greupink, Petra van de Broek, Nashwa Soliman, Samiksha Ghimire, Inge A M de Graaf, Geny M M Groothuis
Drug-induced cholestasis (DIC) is one of the leading manifestations of drug-induced liver injury (DILI). As the underlying mechanisms for DIC are not fully known and specific and predictive biomarkers and pre-clinical models are lacking, the occurrence of DIC is often only reported when the drug has been approved for registration. Therefore, appropriate models that predict the cholestatic potential of drug candidates and/or provide insight into the mechanism of DIC are highly needed. We investigated the application of rat precision-cut liver slices (PCLS) to predict DIC, using several biomarkers of cholestasis: hepatocyte viability, intracellular accumulation of total as well as individual bile acids and changes in the expression of genes known to play a role in cholestasis...
April 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28386637/2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-mediated-deregulation-of-myeloid-and-sebaceous-gland-stem-progenitor-cell-homeostasis
#4
REVIEW
Karl Walter Bock
Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed...
April 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28378122/interplay-between-lysosomal-mitochondrial-and-death-receptor-pathways-during-manganese-induced-apoptosis-in-glial-cells
#5
R M Gorojod, A Alaimo, S Porte Alcon, F Saravia, M L Kotler
Manganese (Mn) is an essential trace metal which plays a critical role in brain physiology by acting as a cofactor for several enzymes. However, upon overexposure, Mn preferentially accumulates within the basal ganglia leading to the development of a Parkinsonism known as Manganism. Data from our group have proved that Mn induces oxidative stress-mediated apoptosis in astrocytoma C6 cells. In the present study we described how cathepsins impact on different steps of each apoptotic cascade. Evidence obtained demonstrated that Mn generates lysosomal membrane permeabilization (LMP) and cathepsin release...
April 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28378121/toxification-of-polycyclic-aromatic-hydrocarbons-by-commensal-bacteria-from-human-skin
#6
Juliane Sowada, Lisa Lemoine, Karsten Schön, Christoph Hutzler, Andreas Luch, Tewes Tralau
The ubiquitous occurrence of polycyclic aromatic hydrocarbons (PAHs) leads to constant human exposure at low levels. Toxicologically relevant are especially the high-molecular weight substances due to their (pro-)carcinogenic potential. Following ingestion or uptake, the eukaryotic phase I metabolism often activates these substances to become potent DNA binders, and unsurprisingly metabolism and DNA-adduct formation of model substances such as benzo[a]pyrene (B[a]P) are well studied. However, apart from being subjected to eukaryotic transformations PAHs are also carbon and energy sources for the myriads of commensal microbes inhabiting man's every surface...
April 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28378120/comprehensive-analysis-of-the-in-vitro-and-ex-ovo-hemocompatibility-of-surface-engineered-iron-oxide-nanoparticles-for-biomedical-applications
#7
Florian Schlenk, Sebastian Werner, Martin Rabel, Franziska Jacobs, Christian Bergemann, Joachim H Clement, Dagmar Fischer
A set of biomedically relevant iron oxide nanoparticles with systematically modified polymer surfaces was investigated regarding their interaction with the first contact partners after systemic administration such as blood cells, blood proteins, and the endothelial blood vessels, to establish structure-activity relationships. All nanoparticles were intensively characterized regarding their physicochemical parameters. Cyto- and hemocompatibility tests showed that (1) the properties of the core material itself were not relevant in short-term incubation studies, and (2) toxicities increased with higher polymer mass, neutral = anionic < cationic surface charge and charge density, as well as agglomeration...
April 4, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28374158/glyphosate-toxicity-and-carcinogenicity-a-review-of-the-scientific-basis-of-the-european-union-assessment-and-its-differences-with-iarc
#8
REVIEW
Jose V Tarazona, Daniele Court-Marques, Manuela Tiramani, Hermine Reich, Rudolf Pfeil, Frederique Istace, Federica Crivellente
Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence...
April 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28374157/chalcone-flavokawain-b-induces-autophagic-cell-death-via-reactive-oxygen-species-mediated-signaling-pathways-in-human-gastric-carcinoma-and-suppresses-tumor-growth-in-nude-mice
#9
Chia-Ting Chang, You-Cheng Hseu, Varadharajan Thiyagarajan, Kai-Yuan Lin, Tzong-Der Way, Mallikarjuna Korivi, Jiuun-Wang Liao, Hsin-Ling Yang
Flavokawain B (FKB), a naturally occurring chalcone in kava extracts, has been reported to possess anticancer activity. However, the effect of FKB on gastric cancer remains unclear. We examined the in vitro and in vivo anticancer activity and autophagy involvement of FKB and determined the underlying molecular mechanisms. FKB is potently cytotoxic to human gastric cancer cells (AGS/NCI-N87/KATO-III/TSGH9201) and mildly toxic towards normal (Hs738) cells and primary mouse hepatocytes. FKB-induced AGS cell death was characterized by autophagy, not apoptosis, as evidenced by increased LC3-II accumulation, GFP-LC3 puncta and acidic vesicular organelles (AVOs) formation, without resulting procaspase-3/PARP cleavage...
April 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28365849/impairment-of-human-neural-crest-cell-migration-by-prolonged-exposure-to-interferon-beta
#10
Giorgia Pallocca, Johanna Nyffeler, Xenia Dolde, Marianna Grinberg, Gerhard Gstraunthaler, Tanja Waldmann, Jörg Rahnenführer, Agapios Sachinidis, Marcel Leist
Human cell-based toxicological assays have been used successfully to detect known toxicants, and to distinguish them from negative controls. However, there is at present little experience on how to deal with hits from screens of compounds with yet unknown hazard. As a case study to this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified as a hit during a screen of clinically used drugs in the 'migration inhibition of neural crest' (MINC) assay...
April 1, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28357488/study-on-inter-ethnic-human-differences-in-bioactivation-and-detoxification-of-estragole-using-physiologically-based-kinetic-modeling
#11
Jia Ning, Jochem Louisse, Bert Spenkelink, Sebastiaan Wesseling, Ivonne M C M Rietjens
Considering the rapid developments in food safety in the past decade in China, it is of importance to obtain insight into what extent safety and risk assessments of chemicals performed for the Caucasian population apply to the Chinese population. The aim of the present study was to determine physiologically based kinetic (PBK) modeling-based predictions for differences between Chinese and Caucasians in terms of metabolic bioactivation and detoxification of the food-borne genotoxic carcinogen estragole. The PBK models were defined based on kinetic constants for hepatic metabolism derived from in vitro incubations using liver fractions of the two ethnic groups, and used to evaluate the inter-ethnic differences in metabolic activation and detoxification of estragole...
March 29, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28357487/lesson-of-15-year-exposure-to-bisphenol-a-a-critical-discussion-of-biomonitoring-studies
#12
LETTER
Wolfgang Völkel
No abstract text is available yet for this article.
March 29, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28357486/the-human-microbiome-from-achilles-armour-to-nessus-shirt
#13
EDITORIAL
Tewes Tralau, Andreas Luch
No abstract text is available yet for this article.
March 29, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28349193/time-matched-analysis-of-dna-adduct-formation-and-early-gene-expression-as-predictive-tool-for-renal-carcinogenesis-in-methylazoxymethanol-acetate-treated-eker-rats
#14
Valentina Klaus, Heinke Bastek, Katja Damme, Leonard B Collins, Roland Frötschl, Norbert Benda, Dominik Lutter, Heidrun Ellinger-Ziegelbauer, James A Swenberg, Daniel R Dietrich, Kerstin Stemmer
Genotoxic carcinogens pose great hazard to human health. Uncertainty of current risk assessment strategies and long latency periods between first carcinogen exposure and diagnosis of tumors have raised interest in predictive biomarkers. Initial DNA adduct formation is a necessary step for genotoxin induced carcinogenesis. However, as DNA adducts not always translate into tumorigenesis, their predictive value is limited. Here we hypothesize that the combined analysis of pro-mutagenic DNA adducts along with time-matched gene expression changes could serve as a superior prediction tool for genotoxic carcinogenesis...
March 27, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28337504/biotransformation-of-2-4-toluenediamine-in-human-skin-and-reconstructed-tissues
#15
Lisa Grohmann, Daniel Becker, Jörg Rademann, Nan Ma, Monika Schäfer-Korting, Günther Weindl
Reconstructed human epidermis (RHE) is used for risk assessment of chemicals and cosmetics and RHE as well as reconstructed human full-thickness skin (RHS) become important for e.g., the pre-clinical development of drugs. Yet, the knowledge regarding their biotransformation capacity is still limited, although the metabolic activity is highly relevant for skin sensitization, genotoxicity, and the efficacy of topical dermatics. The biotransformation of the aromatic amine 2,4-toluenediamine (2,4-TDA) has been compared in two commercially available RHS to normal human skin ex vivo, and in primary epidermal keratinocytes and dermal fibroblasts as well as in vitro generated epidermal Langerhans cells and dermal dendritic cells...
March 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28337503/gut-microbiome-related-metabolic-changes-in-plasma-of-antibiotic-treated-rats
#16
C Behr, H Kamp, E Fabian, G Krennrich, W Mellert, E Peter, V Strauss, T Walk, I M C M Rietjens, B van Ravenzwaay
The intestinal microbiota contributes to the metabolism of its host. Adequate identification of the microbiota's impact on the host plasma metabolites is lacking. As antibiotics have a profound effect on the microbial composition and hence on the mammalian-microbiota co-metabolism, we studied the effects of antibiotics on the "functionality of the microbiome"-defined as the production of metabolites absorbed by the host. This metabolomics study presents insights into the mammalian-microbiome co-metabolism of endogenous metabolites...
March 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28331975/recent-progress-in-n-acetyltransferase-research-7th-international-workshop-on-n-acetyltransferases-nat-workshop-report
#17
Jutta Lichter, Klaus Golka, Edith Sim, Brunhilde Blömeke
The 7th International Workshop on N-Acetyltransferases (NAT), held from 18 to 20 June 2016, was hosted by Brunhilde Blömeke and her team at the Trier University (Germany). The workshop addressed important aspects and latest advancements in the fields of NAT enzymes, endogenous functions of NATs, NAT gene nomenclature, genetic polymorphisms, and their associations with diseases as well as their use in diagnosis. Representatives from the leading teams performing research on NATs presented their excellent work, discussed the latest results, and created new ideas in the field of N-acetyltransferase research...
March 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28326452/methyleugenol-dna-adducts-in-human-liver-are-associated-with-sult1a1-copy-number-variations-and-expression-levels
#18
Roman Tremmel, Kristin Herrmann, Wolfram Engst, Walter Meinl, Kathrin Klein, Hansruedi Glatt, Ulrich M Zanger
Methyleugenol is a rodent hepatocarcinogen occurring in many herbs and spices as well as essential oils used for flavoring. Following metabolic activation by cytochromes P450 (CYPs) and sulfotransferases (SULTs), methyleugenol can form DNA adducts. Previously, we showed that DNA adduct formation by methyleugenol in mouse liver is dependent on SULT1A1 expression and that methyleugenol DNA adducts are abundant in human liver specimens. In humans, SULT1A1 activity is affected by genetic polymorphisms, including single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)...
March 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#19
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28317071/answer-to-the-comment-of-hai-lu-et-al-regarding-hepatotoxicity-by-combination-treatment-of-temozolomide-artesunate-and-chinese-herbs-in-a-glioblastoma-multiforme-patient-case-report-and-review-of-the-literature-arch-toxicol-2016
#20
LETTER
Thomas Efferth, Ursula Schöttler, Sanjeev Krishna, Peter Schmiedek, Frederik Wenz, Frank A Giordano
No abstract text is available yet for this article.
March 19, 2017: Archives of Toxicology
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