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Archives of Toxicology

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https://www.readbyqxmd.com/read/27913847/patulin-transformation-products-and-last-intermediates-in-its-biosynthetic-pathway-e-and-z-ascladiol-are-not-toxic-to-human-cells
#1
Joanna Tannous, Selma P Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, André El Khoury, Ali Atoui, Ting Zhou, Roger Lteif, Isabelle P Oswald, Olivier Puel
Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913846/potent-mutagenicity-of-some-non-planar-tri-and-tetrachlorinated-biphenyls-in-mammalian-cells-human-cyp2e1-being-a-major-activating-enzyme
#2
Yungang Liu, Keqi Hu, Hansi Jia, Guifang Jin, Hansruedi Glatt, Hao Jiang
Polychlorinated biphenyls (PCBs) have been classified as human carcinogens. Mutagenicity of lower chlorinated biphenyls as well as activation of transcription factors by some other congeners may contribute to the carcinogenicity of PCBs. Recently, we reported that human CYP2E1 activates mono- and dichlorobiphenyls to mutagens. However, mutagenicity of other PCBs and the involvement of other CYPs remained unknown. In this study, Chinese hamster V79-derived cell lines genetically engineered for expression of individual human CYP enzymes and a human hepatocyte (L-02) line endogenously expressing various CYPs were used to determine the activities of several tri- and tetrachlorobiphenyls to induce micronuclei and gene mutations...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913845/mitogen-activated-protein-kinases-are-involved-in-hepatocanalicular-dysfunction-and-cholestasis-induced-by-oxidative-stress
#3
Flavia D Toledo, Cecilia L Basiglio, Ismael R Barosso, Andrea C Boaglio, Andrés E Zucchetti, Enrique J Sánchez Pozzi, Marcelo G Roma
In previous studies, we showed that the pro-oxidant model agent tert-butyl hydroperoxide (tBuOOH) induces alterations in hepatocanalicular secretory function by activating Ca(2+)-dependent protein kinase C isoforms (cPKC), via F-actin disorganization followed by endocytic internalization of canalicular transporters relevant to bile formation (Mrp2, Bsep). Since mitogen-activated protein kinases (MAPKs) may be downstream effectors of cPKC, we investigated here the involvement of the MAPKs of the ERK1/2, JNK1/2, and p38(MAPK) types in these deleterious effects...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913844/global-dna-methylation-profiling-of-manganese-exposed-human-neuroblastoma-sh-sy5y-cells-reveals-epigenetic-alterations-in-parkinson-s-disease-associated-genes
#4
Prashant Tarale, Saravanadevi Sivanesan, Atul P Daiwile, Reinhard Stöger, Amit Bafana, Pravin K Naoghare, Devendra Parmar, Tapan Chakrabarti, Krishnamurthi Kannan
Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson's disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson's disease...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#5
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27900403/erratum-to-maintenance-of-drug-metabolism-and-transport-functions-in-human-precision-cut-liver-slices-during-prolonged-incubation-for-5%C3%A2-days
#6
Viktoriia Starokozhko, Suresh Vatakuti, Bauke Schievink, Marjolijn T Merema, Annika Asplund, Jane Synnergren, Anders Aspegren, Geny M M Groothuis
No abstract text is available yet for this article.
November 30, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27900425/erratum-to-aryl-hydrocarbon-receptor-signaling-modifies-toll-like-receptor-regulated-responses-in-human-dendritic-cells
#7
Sarah Kado, W L William Chang, Aimy Nguyen Chi, Monika Wolny, David M Shepherd, Christoph F A Vogel
No abstract text is available yet for this article.
November 29, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27896399/cytochrome-p450-mediated-metabolism-of-triclosan-attenuates-its-cytotoxicity-in-hepatic-cells
#8
Yuanfeng Wu, Priyanka Chitranshi, Lucie Loukotková, Gonçalo Gamboa da Costa, Frederick A Beland, Jie Zhang, Jia-Long Fang
Triclosan is a widely used broad-spectrum anti-bacterial agent. The objectives of this study were to identify which cytochrome P450 (CYP) isoforms metabolize triclosan and to examine the effects of CYP-mediated metabolism on triclosan-induced cytotoxicity. A panel of HepG2-derived cell lines was established, each of which overexpressed a single CYP isoform, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and CYP4B1...
November 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27896398/acute-liver-effects-disposition-and-metabolic-fate-of-14-c-fenclozic-acid-following-oral-administration-to-normal-and-bile-cannulated-male-c57bl-6j-mice
#9
Kathryn Pickup, Scott Martin, Elizabeth A Partridge, Huw B Jones, Jonathan Wills, Tim Schulz-Utermoehl, Alan McCarthy, Alison Rodrigues, Chris Page, Kerry Ratcliffe, Sunil Sarda, Ian D Wilson
The distribution, metabolism, excretion and hepatic effects of the human hepatotoxin fenclozic acid were investigated following single oral doses of 10 mg/kg to normal and bile duct-cannulated male C57BL/6J mice. Whole body autoradiography showed distribution into all tissues except the brain, with radioactivity still detectable in blood, kidney and liver at 72 h post-dose. Mice dosed with [(14)C]-fenclozic acid showed acute centrilobular hepatocellular necrosis, but no other regions of the liver were affected...
November 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27858113/a-framework-for-the-use-of-single-chemical-transcriptomics-data-in-predicting-the-hazards-associated-with-complex-mixtures-of-polycyclic-aromatic-hydrocarbons
#10
Sarah Labib, Andrew Williams, Byron Kuo, Carole L Yauk, Paul A White, Sabina Halappanavar
The assumption of additivity applied in the risk assessment of environmental mixtures containing carcinogenic polycyclic aromatic hydrocarbons (PAHs) was investigated using transcriptomics. MutaTMMouse were gavaged for 28 days with three doses of eight individual PAHs, two defined mixtures of PAHs, or coal tar, an environmentally ubiquitous complex mixture of PAHs. Microarrays were used to identify differentially expressed genes (DEGs) in lung tissue collected 3 days post-exposure. Cancer-related pathways perturbed by the individual or mixtures of PAHs were identified, and dose-response modeling of the DEGs was conducted to calculate gene/pathway benchmark doses (BMDs)...
November 17, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27853831/role-of-the-lipid-regulated-nf-%C3%AE%C2%BAb-il-6-stat3-axis-in-alpha-naphthyl-isothiocyanate-induced-liver-injury
#11
Zhong-Ze Fang, Naoki Tanaka, Dan Lu, Chang-Tao Jiang, Wei-Hua Zhang, Chunze Zhang, Zuo Du, Zhi-Wei Fu, Peng Gao, Yun-Feng Cao, Hong-Zhi Sun, Zhi-Tu Zhu, Yan Cai, Kristopher W Krausz, Zhi Yao, Frank J Gonzalez
Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1...
November 16, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27847981/knockout-of-arsenic-3-oxidation-state-methyltransferase-is-associated-with-adverse-metabolic-phenotype-in-mice-the-role-of-sex-and-arsenic-exposure
#12
Christelle Douillet, Madelyn C Huang, R Jesse Saunders, Ellen N Dover, Chongben Zhang, Miroslav Stýblo
Susceptibility to toxic effects of inorganic arsenic (iAs) depends, in part, on efficiency of iAs methylation by arsenic (+3 oxidation state) methyltransferase (AS3MT). As3mt-knockout (KO) mice that cannot efficiently methylate iAs represent an ideal model to study the association between iAs metabolism and adverse effects of iAs exposure, including effects on metabolic phenotype. The present study compared measures of glucose metabolism, insulin resistance and obesity in male and female wild-type (WT) and As3mt-KO mice during a 24-week exposure to iAs in drinking water (0...
November 15, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27838757/transcriptomics-and-methylomics-of-cd4-positive-t-cells-in-arsenic-exposed-women
#13
Karin Engström, Tomasz K Wojdacz, Francesco Marabita, Philip Ewels, Max Käller, Francesco Vezzi, Nicola Prezza, Joel Gruselius, Marie Vahter, Karin Broberg
Arsenic, a carcinogen with immunotoxic effects, is a common contaminant of drinking water and certain food worldwide. We hypothesized that chronic arsenic exposure alters gene expression, potentially by altering DNA methylation of genes encoding central components of the immune system. We therefore analyzed the transcriptomes (by RNA sequencing) and methylomes (by target-enrichment next-generation sequencing) of primary CD4-positive T cells from matched groups of four women each in the Argentinean Andes, with fivefold differences in urinary arsenic concentrations (median concentrations of urinary arsenic in the lower- and high-arsenic groups: 65 and 276 μg/l, respectively)...
November 12, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27837308/polychlorinated-biphenyls-exposure-induced-insulin-resistance-is-mediated-by-lipid-droplet-enlargement-through-fsp27
#14
Hye Young Kim, Woo Young Kwon, Yeon A Kim, Yoo Jin Oh, Seung Hee Yoo, Mi Hwa Lee, Ju Yong Bae, Jong-Min Kim, Young Hyun Yoo
Although epidemiological and experimental studies demonstrated that polychlorinated biphenyls (PCBs) lead to insulin resistance, the mechanism underlying PCBs-induced insulin resistance has remained unsolved. In this study, we examined in vitro and in vivo effects of PCB-118 (dioxin-like PCB) and PCB-138 (non-dioxin-like PCB) on adipocyte differentiation, lipid droplet growth, and insulin action. 3T3-L1 adipocytes were incubated with PCB-118 or PCB-138 during adipocyte differentiation. For in vivo studies, C57BL/6 mice were administered PCB-118 or PCB-138 (37...
November 11, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27832320/activation-of-nuclear-receptor-car-by-an-environmental-pollutant-perfluorooctanoic-acid
#15
Taiki Abe, Mirei Takahashi, Makoto Kano, Yuto Amaike, Chizuru Ishii, Kazuhiro Maeda, Yuki Kudoh, Toru Morishita, Takuomi Hosaka, Takamitsu Sasaki, Susumu Kodama, Atsushi Matsuzawa, Hiroyuki Kojima, Kouichi Yoshinari
Perfluorocarboxylic acids (PFCAs) including perfluorooctanoic acid (PFOA) are environmental pollutants showing high accumulation, thermochemical stability and hepatocarcinogenicity. Peroxisome proliferator-activated receptor α is suggested to mediate their toxicities, but the precise mechanism remains unclear. Previous reports also imply a possible role of constitutive androstane receptor (CAR), a key transcription factor for the xenobiotic-induced expression of various genes involved in drug metabolism and disposition as well as hepatocarcinogenesis...
November 10, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27830268/butyrate-alters-expression-of-cytochrome-p450-1a1-and-metabolism-of-benzo-a-pyrene-via-its-histone-deacetylase-activity-in-colon-epithelial-cell-models
#16
Ondřej Zapletal, Zuzana Tylichová, Jiří Neča, Jiří Kohoutek, Miroslav Machala, Alena Milcová, Michaela Pokorná, Jan Topinka, Mary Pat Moyer, Jiřina Hofmanová, Alois Kozubík, Jan Vondráček
Butyrate, a short-chain fatty acid produced by fermentation of dietary fiber, is an important regulator of colonic epithelium homeostasis. In this study, we investigated the impact of this histone deacetylase (HDAC) inhibitor on expression/activity of cytochrome P450 family 1 (CYP1) and on metabolism of carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells...
November 9, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27830267/response-to-druwe-and-burgoon-2016-letter-to-the-editor-in-archives-of-toxicology
#17
EDITORIAL
Samuel M Cohen, Jay I Goodman, James E Klaunig, Lora L Arnold
No abstract text is available yet for this article.
November 9, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27826632/inhibition-of-pannexin1-channels-alleviates-acetaminophen-induced-hepatotoxicity
#18
Michaël Maes, Mitchell R McGill, Tereza Cristina da Silva, Chloé Abels, Margitta Lebofsky, James L Weemhoff, Taynã Tiburcio, Isabel Veloso Alves Pereira, Joost Willebrords, Sara Crespo Yanguas, Anwar Farhood, Alain Beschin, Jo A Van Ginderachter, Silvia Penuela, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia-reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity. Hepatic expression of pannexin1 was characterized in a mouse model of acetaminophen-induced hepatotoxicity...
November 8, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27815601/integrating-in-vitro-data-and-physiologically-based-kinetic-pbk-modelling-to-assess-the-in-vivo-potential-developmental-toxicity-of-a-series-of-phenols
#19
Marije Strikwold, Bert Spenkelink, Laura H J de Haan, Ruud A Woutersen, Ans Punt, Ivonne M C M Rietjens
Toxicity outcomes derived in vitro do not always reflect in vivo toxicity values, which was previously observed for a series of phenols tested in the embryonic stem cell test (EST). Translation of in vitro data to the in vivo situation is therefore an important, but still limiting step for the use of in vitro toxicity outcomes in the safety assessment of chemicals. The aim of the present study was to translate in vitro embryotoxicity data for a series of phenols to in vivo developmental toxic potency values for the rat by physiologically based kinetic (PBK) modelling-based reverse dosimetry...
November 4, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27815600/highlight-report-high-resolution-mass-spectrometry
#20
EDITORIAL
Meinolf Blaszkewicz
No abstract text is available yet for this article.
November 4, 2016: Archives of Toxicology
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