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Archives of Toxicology

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https://www.readbyqxmd.com/read/28821999/developmental-neurotoxicity-of-the-hippocampus-following-in-utero-exposure-to-methylmercury-impairment-in-cell-signaling
#1
Luana Heimfarth, Jeferson Delgado, Moara Rodrigues Mignori, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Regina Pessoa-Pureur
In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.0 mg/kg MeHg by gavage in alternated days from gestational day 5 until parturition. We found increased anxiety-like and decreased exploration behavior evaluated by open field test and deficit of both short- and long-term memories by novel object recognition task, respectively, in MeHg-treated pups. Downregulated PI3K/Akt/mTOR pathway and activated/hypophosphorylated (Ser9) GSK3β in MeHg-treated pups could be upstream of hyperphosphorylated Tau (Ser396) destabilizing microtubules and contributing to neural dysfunction in the hippocampus of these rats...
August 18, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28799093/an-appraisal-of-critical-effect-sizes-for-the-benchmark-dose-approach-to-assess-dose-response-relationships-in-genetic-toxicology
#2
Andreas Zeller, Gonzalo Duran-Pacheco, Melanie Guérard
The benchmark dose (BMD) concept is increasingly utilized to analyze quantitative dose-response relationships in genetic toxicology. This methodology requires the user (i.e. the toxicologist) to a priori define a small increase over controls that is "acceptable" to be induced by a genotoxic test substance. The increase is called benchmark response (BMR) or critical effect size (CES), depending on the software used. To render the metrics calculated from the data of animals treated with the test substance applicable for risk assessment, the BMR or CES must represent biologically relevant changes of parameters measured in in vivo genotoxicity assays such as the Micronucleus, Comet, Transgenic rodent or Pig-a assay...
August 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28776197/long-term-exposure-of-immortalized-keratinocytes-to-arsenic-induces-emt-impairs-differentiation-in-organotypic-skin-models-and-mimics-aspects-of-human-skin-derangements
#3
R Weinmuellner, K Kryeziu, B Zbiral, K Tav, B Schoenhacker-Alte, D Groza, L Wimmer, M Schosserer, F Nagelreiter, S Rösinger, M Mildner, E Tschachler, M Grusch, J Grillari, P Heffeter
Arsenic is one of the most important human carcinogens and environmental pollutants. However, the evaluation of the underlying carcinogenic mechanisms is challenging due to the lack of suitable in vivo and in vitro models, as distinct interspecies differences in arsenic metabolism exist. Thus, it is of high interest to develop new experimental models of arsenic-induced skin tumorigenesis in humans. Consequently, aim of this study was to establish an advanced 3D model for the investigation of arsenic-induced skin derangements, namely skin equivalents, built from immortalized human keratinocytes (NHEK/SVTERT3-5)...
August 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28776196/erratum-to-prenatal-nicotine-exposure-induces-hpa-axis-hypersensitivity-in-offspring-rats-via-the-intrauterine-programming-of-up-regulation-of-hippocampal-gad67
#4
Xia He, Juan Lu, Wanting Dong, Zhexiao Jiao, Chong Zhang, Ying Yu, Zhaohui Zhang, Hui Wang, Dan Xu
No abstract text is available yet for this article.
August 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28766123/screening-the-toxcast-phase-ii-libraries-for-alterations-in-network-function-using-cortical-neurons-grown-on-multi-well-microelectrode-array-mwmea-plates
#5
Jenna D Strickland, Matthew T Martin, Ann M Richard, Keith A Houck, Timothy J Shafer
Methods are needed for rapid screening of environmental compounds for neurotoxicity, particularly ones that assess function. To demonstrate the utility of microelectrode array (MEA)-based approaches as a rapid neurotoxicity screening tool, 1055 chemicals from EPA's phase II ToxCast library were evaluated for effects on neural function and cell health. Primary cortical networks were grown on multi-well microelectrode array (mwMEA) plates. On day in vitro 13, baseline activity (40 min) was recorded prior to exposure to each compound (40 µM)...
August 2, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28762043/customised-in-vitro-model-to-detect-human-metabolism-dependent-idiosyncratic-drug-induced-liver-injury
#6
Laia Tolosa, Nuria Jiménez, Gabriela Pérez, José V Castell, M José Gómez-Lechón, M Teresa Donato
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI...
July 31, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28733891/consequences-of-bisphenol-a-perinatal-exposure-on-immune-responses-and-gut-barrier-function-in-mice
#7
Yann Malaisé, Sandrine Ménard, Christel Cartier, Corinne Lencina, Caroline Sommer, Eric Gaultier, Eric Houdeau, Laurence Guzylack-Piriou
The potent immunomodulatory effect of the endocrine disruptor bisphenol A during development and consequences during life span are of increasing concern. Particular interests have been raised from animal studies regarding the risk of developing food intolerance and infection. We aimed to identify immune disorders in mice triggered by perinatal exposure to bisphenol A. Gravid mice were orally exposed to bisphenol (50 μg/kg body weight/day) from day 15 of pregnancy until weaning. Gut barrier function, local and systemic immunity were assessed in adult female offspring...
July 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28733890/down-regulation-of-mirna-451a-and-mirna-486-5p-involved-in-benzene-induced-inhibition-on-erythroid-cell-differentiation-in-vitro-and-in-vivo
#8
Boxuan Liang, Yuncong Chen, Weixin Yuan, Fei Qin, Qian Zhang, Na Deng, Xuexing Liu, Xiaoju Ma, Xue Zhang, Bo Zhang, Qifei Deng, Ming Huang, Huanwen Tang, Linhua Liu, Wen Chen, Yongmei Xiao
Exposure to high-dose benzene leads to the inhibition of erythroid differentiation. However, whether lower doses of benzene exposure resemble high-dose effects in erythroid differentiation, as well as the underlying mechanisms, remains largely unknown. To identify the microRNAs (miRNAs) specifically responsible for benzene exposure and their regulatory role in erythroid differentiation, we performed miRNA microarray in CD34(+) hematopoietic progenitor cells isolated from human umbilical cord blood after treatment with hydroquinone (HQ), a metabolite of benzene at concentrations of 0, 1...
July 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28733889/comment-on-asghari-et-al-2017-on-the-mechanisms-of-melatonin-in-protection-of-aluminum-phosphide-cardiotoxicity-arch-toxicol-epub-ahead-of-print-doi-10-1007-s00204-017-1998-6
#9
LETTER
https://www.readbyqxmd.com/read/28733888/in-response-to-the-comments-on-our-recently-published-paper-entitled-on-the-mechanisms-of-melatonin-in-protection-of-aluminum-phosphide-cardiotoxicity
#10
LETTER
Mohammad Hossein Asghari, Milad Moloudizargari, Mohammad Abdollahi
No abstract text is available yet for this article.
July 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28733887/erratum-to-modelling-foetal-exposure-to-maternal-smoking-using-hepatoblasts-from-pluripotent-stem-cells
#11
Baltasar Lucendo-Villarin, Panagiotis Filis, Madeleine J Swortwood, Marilyn A Huestis, Jose Meseguer-Ripolles, Kate Cameron, John P Iredale, Peter J O'Shaughnessy, Paul A Fowler, David C Hay
No abstract text is available yet for this article.
July 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28725974/carbofuran-causes-neuronal-vulnerability-to-glutamate-by-decreasing-glua2-protein-levels-in-rat-primary-cortical-neurons
#12
Kanae Umeda, Masatsugu Miyara, Keishi Ishida, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Glutamate receptor 2 (GluA2/GluR2) is one of the four subunits of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR); an increase in GluA2-lacking AMPARs contributes to neuronal vulnerability to excitotoxicity because of the receptor's high Ca(2+) permeability. Carbofuran is a carbamate pesticide used in agricultural areas to increase crop productivity. Due to its broad-spectrum action, carbofuran has also been used as an insecticide, nematicide, and acaricide. In this study, we investigated the effect of carbofuran on GluA2 protein expression...
July 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28721440/selectivity-of-plasma-membrane-calcium-atpase-pmca-mediated-extrusion-of-toxic-divalent-cations-in-vitro-and-in-cultured-cells
#13
Mariela S Ferreira-Gomes, Irene C Mangialavori, Mallku Q Ontiveros, Debora E Rinaldi, Jorge Martiarena, Sandra V Verstraeten, Juan Pablo F C Rossi
In the recent years, the toxicity of certain divalent cations has been associated with the alteration of intracellular Ca(2+) homeostasis. Among other mechanisms, these cations may affect the functionality of certain Ca(2+)-binding proteins and/or Ca(2+) pumps. The plasma membrane calcium pump (PMCA) maintains Ca(2+) homeostasis in eukaryotic cells by mediating the efflux of this cation in a process coupled to ATP hydrolysis. The aim of this work was to investigate both in vitro and in cultured cells if other divalent cations (Sr(2+), Ba(2+), Co(2+), Cd(2+), Pb(2+) or Be(2+)) could be transported by PMCA...
July 18, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#14
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28710503/rac1-mediated-cardiac-damage-causes-diastolic-dysfunction-in-a-mouse-model-of-subacute-doxorubicin-induced-cardiotoxicity
#15
Jan Ohlig, Christian Henninger, Simone Zander, Marc Merx, Malte Kelm, Gerhard Fritz
The anticancer efficacy of anthracyclines is limited by congestive heart failure. Clinically established markers of early onset of cardiotoxicity following anthracycline treatment and preventive measures are missing. Although statins are reported to alleviate anthracycline-induced cardiotoxicity in vivo, the molecular mechanisms involved remain elusive. In vitro data point to Rac1 as major target of the cytoprotective statin effects. Here we investigated whether specific inhibition of Rac1 by NSC23766 is as effective as lovastatin in preventing subacute cardiotoxicity following doxorubicin treatment...
July 14, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28707023/oxidative-inactivation-of-the-endogenous-antioxidant-protein-dj-1-by-the-food-contaminants-3-mcpd-and-2-mcpd
#16
Thorsten Buhrke, Linn Voss, Anja Briese, Heike Stephanowitz, Eberhard Krause, Albert Braeuning, Alfonso Lampen
3-Chloro-1,2-propanediol (3-MCPD) and 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants being present either as free substances or as fatty acid esters in numerous foods. 3-MCPD was classified to be possibly carcinogenic to humans (category 2B) with kidney and testis being the primary target organs according to animal studies. A previous 28-day oral feeding study with rats revealed that the endogenous antioxidant protein DJ-1 was strongly deregulated at the protein level in kidney, liver, and testis of the experimental animals that had been treated either with 3-MCPD, 2-MCPD or their dipalmitate esters...
July 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28702692/reply-to-the-commentary-by-lotti-m-and-moretto-a-organophosphate-neurotoxicity-to-the-voluntary-motor-system-on-the-trail-of-environment-caused-amyotrophic-lateral-sclerosis-the-known-the-misknown-and-the-unknown
#17
LETTER
Samantha J Merwin, Teresa Obis, Yanelli Nunez, Diane B Re
No abstract text is available yet for this article.
July 12, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28702691/toxic-effects-and-biodistribution-of-ultrasmall-gold-nanoparticles
#18
REVIEW
Günter Schmid, Wolfgang G Kreyling, Ulrich Simon
Gold nanoparticles (AuNPs) have been extensively explored in biomedical applications, for example as drug carriers, contrast agents, or therapeutics. However, AuNP can exhibit cytotoxic profile, when the size is below 2 nm (ultrasmall AuNP; usAuNP) and when the stabilizing ligands allow for access to the gold surface either for the direct interaction with biomolecules or for catalytic activity of the unshielded gold surface. Furthermore, usAuNP exhibits significantly different biodistribution and enhanced circulation times compared to larger AuNP...
July 12, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28695231/erratum-to-role-of-the-aryl-hydrocarbon-receptor-in-carcinogenesis-and-potential-as-an-anti-cancer-drug-target
#19
Siva Kumar Kolluri, Un-Ho Jin, Stephen Safe
No abstract text is available yet for this article.
July 11, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28681081/genome-wide-mapping-and-analysis-of-aryl-hydrocarbon-receptor-ahr-and-aryl-hydrocarbon-receptor-repressor-ahrr-binding-sites-in-human-breast-cancer-cells
#20
Sunny Y Yang, Shaimaa Ahmed, Somisetty V Satheesh, Jason Matthews
The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24 h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq)...
July 5, 2017: Archives of Toxicology
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