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Toxicological Sciences: An Official Journal of the Society of Toxicology

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https://www.readbyqxmd.com/read/30535411/generalized-concentration-addition-model-predicts-glucocorticoid-activity-bioassay-responses-to-environmentally-detected-receptor-ligand-mixtures
#1
Elizabeth Medlock Kakaley, Mary C Cardon, L Earl Gray, Phillip C Hartig, Vickie S Wilson
Many glucocorticoid receptor (GR) agonists have been detected in waste and surface waters domestically and around the world, but the way a mixture of these environmental compounds may elicit a total glucocorticoid activity response in water samples remains unknown. Therefore, we characterized 19 GR ligands using a CV1 cell line transcriptional activation assay applicable to water quality monitoring. Cells were treated with individual GR ligands, a fixed ratio mixture of full or partial agonists, or a non-equipotent mixture with full and partial agonists...
December 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30535317/kidney-toxicity-and-response-of-selenium-containing-protein-glutathione-peroxidase-gpx3-to-cdte-qds-on-different-levels
#2
Lining Zhao, Wansong Zong, Hao Zhang, Rutao Liu
The toxic mechanism of cadmium-quantum dot (Cd-QDs) to organisms is still debating. In this paper, it was found that Cd-QDs could induce adverse effects to kidney by entering into cells in a time and dose manner and disturbing the redox balance in vivo. As a selenium containing protein, glutathione peroxidase3 (Gpx3) plays a crucial role in maintaining the balance of redox system. The decrease of Gpx3 activity might be related to the imbalance of redox system. Similar to the animal results, it was demonstrated that Gpx3 activity is also inhibited by Cd-QDs in vitro...
December 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30535037/the-gmo90-project-absence-of-evidence-for-biologically-meaningful-effects-of-genetically-modified-maize-based-diets-on-wistar-rats-after-6-months-feeding-comparative-trial
#3
Xavier Coumoul, Rémi Servien, Ludmila Juricek, Yael Kaddouch-Amar, Yannick Lippi, Laureline Berthelot, Claire Naylies, Marie-Line Morvan, Jean-Philippe Antignac, Desdoits-Lethimonier Christèle, Bernard Jegou, Marie Tremblay-Franco, Cécile Canlet, Laurent Debrauwer, Caroline Le Gall, Julie Laurent, Pierre-Antoine Gouraud, Jean-Pierre Cravedi, Elisabeth Jeunesse, Nicolas Savy, Kadidiatou Dandere-Abdoulkarim, Nathalie Arnich, Franck Fourès, Jérome Cotton, Simon Broudin, Bruno Corman, Annick Moing, Bérengère Laporte, Florence Richard-Forget, Robert Barouki, Peter Rogowsky, Bernard Salles
The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to two genetically-modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for six-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33 % with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial...
December 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30521027/detection-and-prioritization-of-developmentally-neurotoxic-and-or-neurotoxic-compounds-using-zebrafish
#4
Celia Quevedo, Mamta Behl, Kristen Ryan, Richard S Paules, Aintzane Alday, Arantza Muriana, Ainhoa Alzualde
The standard methods for toxicity testing using rodent models cannot keep pace with the increasing number of chemicals in our environment due to time and resource limitations. Hence, there is an unmet need for fast, sensitive and cost-effective alternate models to reliably predict toxicity. As part of Tox21 Phase III's effort, a 90-compound library was created and made available to researchers to screen for neurotoxicants using novel technology and models. The chemical library was evaluated in zebrafish in a dose range finding test for embryo-toxicity (i...
December 5, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30517764/paradoxical-effects-of-emodin-on-anit-induced-intrahepatic-cholestasis-and-herb-induced-hepatotoxicity-in-mice
#5
Xue Wang, Lifeng Han, Yajuan Bi, Caiyu Li, Xiumei Gao, Guanwei Fan, Youcai Zhang
Emodin is an active ingredient in many herbal medicines and has a broad spectrum of pharmacological activities. The current data indicate that emodin exerts its beneficial effect on alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis through its anti-oxidant and anti-inflammatory activities. Emodin has little effect on the concentrations of bile acids (BAs) in livers of ANIT-treated mice. Instead, emodin shows a potential pro-cholestatic effect by interfering with the crosstalk between AMP-activated protein kinase (AMPK) and farnesoid X receptor (Fxr) in the liver, which leads to a suppression of bile salt export pump (Bsep)...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30517762/histopathological-and-molecular-signatures-of-a-mouse-model-of-acute-on-chronic-alcoholic-liver-injury-demonstrate-concordance-with-human-alcoholic-hepatitis
#6
Shinji Furuya, Joseph A Cichocki, Kranti Konganti, Kostiantyn Dreval, Takeki Uehara, Yuuki Katou, Hisataka Fukushima, Hiroshi Kono, Igor P Pogribny, Josepmaria Argemi, Ramon Bataller, Ivan Rusyn
Human alcoholic hepatitis (AH) carries a high mortality rate. AH is an acute-on-chronic form of liver injury characterized by hepatic steatosis, ballooned hepatocytes, neutrophil infiltration, and pericellular fibrosis. We aimed to study the pathogenesis of AH in an animal model which combines chronic hepatic fibrosis with intragastric alcohol administration. Adult male C57BL6/J mice were treated with CCl4 (0.2 ml/kg, 2×weekly by intraperitoneal injections for 6 weeks) to induce chronic liver fibrosis. Then, ethyl alcohol (up to 25 g/kg/day for 3 weeks) was administered continuously to mice via a gastric feeding tube, with or without one-half dose of CCl4...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30517752/associations-between-immune-phenotype-and-inflammation-in-murine-models-of-irritant-contact-dermatitis
#7
Kaitlin N Calhoun, Lerin R Luckett-Chastain, Benjamin Frempah, Randle M Gallucci
Irritant contact dermatitis (ICD), the most common occupational cutaneous illness, is an acute inflammatory response caused by topical irritant exposure. Multiple factors are associated with the manifestation and severity of ICD and contribute to the lack of effective prophylactic and treatment strategies. To determine the pathomechanism of ICD caused by the irritants, benzalkonium chloride (BKC) and JP-8 jet fuel, two mouse strains, C57BL/6 and Balb/c, were assessed due to their differential immune predispositions...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30517741/the-isoniazid-metabolites-hydrazine-and-pyridoxal-isonicotinoyl-hydrazone-modulate-heme-biosynthesis
#8
Christopher Trent Brewer, Lei Yang, Anne Edwards, Yan Lu, Jonathan Low, Jing Wu, Richard E Lee, Taosheng Chen
In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase in protoporphyrin IX (PPIX), the penultimate heme precursor. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to upregulate Alas1 but downregulate Fech protein levels in mice; however, the mechanism by which isoniazid mediates disruption of heme synthesis has been unclear...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30517707/transient-receptor-potential-ion-channels-mediate-adherens-junctions-dysfunction-in-a-toluene-diisocyanate-induced-murine-asthma-model
#9
Lihong Yao, Shuyu Chen, Haixiong Tang, Peikai Huang, Shushan Wei, Zhenyu Liang, Ailin Tao, Qingling Zhang, Rongchang Chen
Disruption of epithelial cell-cell junctions is essential for the initiation and perpetuation of airway inflammation in asthma. We've previously reported compromised epithelial barrier integrity in a toluene diisocyanate (TDI)-induced occupational asthma model. This study is aimed to explore the role of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1) in the dysfunction of adherens junctions in TDI-induced asthma. Mice were sensitized and challenged with TDI for a chemical-induced asthma model...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30500950/inhalation-of-zno-nanoparticles-splice-junction-expression-and-alternative-splicing-in-mice
#10
Pavel Rossner, Kristyna Vrbova, Simona Strapacova, Andrea Rossnerova, Antonin Ambroz, Tana Brzicova, Helena Libalova, Eliska Javorkova, Pavel Kulich, Zbynek Vecera, Pavel Mikuska, Pavel Coufalik, Kamil Krumal, Lukas Capka, Bohumil Docekal, Pavel Moravec, Omar Sery, Ivan Misek, Petr Fictum, Karel Fiser, Miroslav Machala, Jan Topinka
Despite the wide application of nanomaterials, toxicity studies of nanoparticles (NP) are often limited to in vitro cell models, and the biological impact of NP exposure in mammals has not been thoroughly investigated. Zinc oxide (ZnO) NP are commonly used in various consumer products. To evaluate the effects of the inhalation of ZnO NP in mice, we studied splice junction expression in the lungs as a proxy to gene expression changes analysis. Female ICR mice were treated with 6.46x104 and 1.93x106 NP/cm3 for three days and three months respectively...
November 30, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30500944/missing-the-difference-between-big-data-artificial-intelligence-in-rasar-versus-traditional-qsar
#11
Thomas Luechtefeld, Dan Marsh, Thomas Hartung
No abstract text is available yet for this article.
November 30, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30500930/oy-vey-a-comment-on-machine-learning-of-toxicological-big-data-enables-read-across-structure-activity-relationships-rasar-outperforming-animal-test-reproducibility
#12
Vinicius M Alves, Joyce Borba, Stephen J Capuzzi, Eugene Muratov, Carolina H Andradi, Ivan Rusyn, Alexander Tropsha
No abstract text is available yet for this article.
November 30, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30500929/freshwater-cyanotoxin-cylindrospermopsin-has-detrimental-stage-specific-effects-on-hepatic-differentiation-from-human-embryonic-stem-cells
#13
Tereza Vanova, Jan Raska, Pavel Babica, Iva Sovadinova, Michaela Kunova Bosakova, Petr Dvorak, Ludek Blaha, Vladimir Rotrekl
Cylindrospermopsin (CYN) has been recognized as a potent waterborne hepatotoxin with an increasing environmental occurrence. However, CYN effects on the specific populations of hepatic cells involved in liver tissue development, renewal and regeneration, have not been characterized yet. We used human embryonic stem cells to analyze the hepatic differentiation stage-specific effect of CYN. Our results strongly suggest that CYN might contribute to the development of chronic adverse outcomes by disrupting liver tissue homeostasis in terms of (i) cellular stress and damage induced in the mature differentiated hepatocytes, which was associated with a necrotic cell death and thus possibly also inflammatory responses; (ii) selective elimination of HNF4α+ cells from populations of progenitor cells and immature hepatocytes during hepatic differentiation, which could possibly lead to an impaired liver renewal and regeneration; (iii) impaired hepatic functions of immature hepatocytes, such as decreased ALB secretion or increased lipid accumulation, which could contribute to the development of liver steatosis; and (iv) survival of the immature and AFP-expressing cells with the limited ability to further differentiate, which could represent a tumor-promoting condition...
November 30, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30496580/screening-for-developmental-neurotoxicity-at-the-national-toxicology-program-the-future-is-here
#14
Mamta Behl, Kristen Ryan, Jui-Hua Hsieh, Frederick Parham, Andrew J Shapiro, Bradley J Collins, Nisha S Sipes, Linda S Birnbaum, John R Bucher, Paul M D Foster, Nigel J Walker, Richard S Paules, Raymond R Tice
The National Toxicology Program (NTP) receives requests to evaluate chemicals with potential to cause adverse health effects, including developmental neurotoxicity (DNT). Some recent requests have included classes of chemicals such as flame retardants, polycyclic aromatic compounds, perfluoroalkyl substances, and bisphenol A analogs with approximately 20 - 50 compounds per class, many of which include commercial mixtures. However, all the compounds within a class cannot be tested using traditional DNT animal testing guideline studies due to resource and time limitations...
November 28, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30496518/a-performance-evaluation-of-liver-and-skeletal-muscle-specific-mirnas-in-rat-plasma-to-detect-drug-induced-injury
#15
Wendy J Bailey, John E Barnum, Zoltan Erdos, Lisa LaFranco-Scheuch, Pamela Lane, Katerina Vlasakova, Frank D Sistare, Warren E Glaab
Liver and skeletal muscle specific microRNAs (miRNAs) are currently being evaluated as novel plasma biomarkers that may out-perform or add value to the conventional liver injury biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and to the skeletal muscle injury biomarkers AST and creatine kinase (CK). A comprehensive evaluation was conducted to assess the relative performance of these miRNAs to detect and distinguish liver from muscle tissue injury. The performance of miR-122 and miR-192 for liver and miR-1, miR-133a, miR-133b, and miR-206 for skeletal muscle was compared to 10 enzymatic or protein biomarkers across 27 compounds causing specific types of tissue injury in rat...
November 28, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30476341/all-trans-retinoic-acid-disrupts-development-in-ex-vivo-cultured-fetal-rat-testes-ii-modulation-of-mono-2-ethylhexyl-phthalate-toxicity
#16
Daniel J Spade, Susan J Hall, Jeremy D Wortzel, Gerardo Reyes, Kim Boekelheide
Humans are universally exposed to low levels of phthalate esters (phthalates), which are used to plasticize polyvinyl chloride. Phthalates exert adverse effects on the development of seminiferous cords in the fetal testis through unknown toxicity pathways. To investigate the hypothesis that phthalates alter seminiferous cord development by disrupting retinoic acid signaling in the fetal testis, gestational day 15 fetal rat testes were exposed for 1-3 days to 10-6 M all-trans retinoic acid (ATRA) alone or in combination with 10-6 to 10-4 M mono-(2-ethylhexyl) phthalate (MEHP) in ex vivo culture...
November 26, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30476324/doxorubicin-induces-er-calcium-release-via-src-in-rat-ovarian-follicles
#17
Aziz Ur Rehman Aziz, Shenyang Geng, Li Wang, Xiaohui Yu, Kai-Rong Qin, Hanqin Wang, Bo Liu
Although doxorubicin has been widely used as an anticancer drug, it has dose-dependent toxic effects on ovarian follicle development and apoptosis, oocyte maturation and hormone secretion. Ca2+ signaling also has vital roles in the same cellular functions of ovarian follicles, indicating a strong link with doxorubicin-induced ovarian toxicity. In the current project, doxorubicin induced Ca2+ alternations in cultured rat ovarian follicles have been explored with the fluorescence resonance energy transfer technology...
November 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30476307/international-regulatory-and-scientific-effort-for-improved-developmental-neurotoxicity-testing
#18
Magdalini Sachana, Anna Bal-Price, Kevin M Crofton, Susanne H Bennekou, Timothy J Shafer, Mamta Behl, Andrea Terron
The Organisation for Economic Co-Operation and Development (OECD) coordinates international efforts to enhance developmental neurotoxicity (DNT) testing. In most regulatory sectors, including the ones dealing with pesticides and industrial chemicals registration, historical use of the in vivo DNT test guideline has been limited. Current challenges include a lack of DNT data and mechanistic information for thousands of chemicals, and difficulty in interpreting results. A series of workshops in the last decade has paved the way for a consensus among stakeholders that there is need for a DNT testing battery that relies on in vitro endpoints (proliferation, differentiation, synaptogenesis, etc...
November 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30462329/fasudil-a-rock-inhibitor-recovers-methylmercury-induced-axonal-degeneration-by-changing-microglial-phenotype-in-rats
#19
Masatake Fujimura, Fusako Usuki, Atsushi Nakamura
Methylmercury is an environmental neurotoxicant that induces neuropathological changes. In this study, we established chronic methylmercury-intoxicated rats. These rats survived, and sustained methylmercury-induced axonal degeneration, including the dorsal root nerve and the dorsal column of the spinal cord; these changes persisted 12 weeks after methylmercury withdrawal. We demonstrated for the first time the restorative effect of Fasudil, a specific inhibitor of Rho-associated coiled coil-forming protein kinase, on axonal degeneration and corresponding neural dysfunction in the established chronic methylmercury-intoxicated rats...
November 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30452740/exposure-to-1-2-dichloropropane-upregulates-the-expression-of-activation-induced-cytidine-deaminase-aid-in-human-cholangiocytes-co-cultured-with-macrophages
#20
Cai Zong, Yusuke Kimura, Kazuo Kinoshita, Shigetada Takasu, Xiao Zhang, Toshihiro Sakurai, Yoshitaka Sekido, Sahoko Ichihara, Ginji Endo, Gaku Ichihara
Background: 1,2-dichloropropane (1,2-DCP) was reclassified recently by IARC as a Group 1 carcinogen based on epidemiological studies on an outbreak of cholangiocarcinoma in offset-printing workers exposed to 1,2-DCP in Japan. However, the underlying mechanism of 1,2-DCP-induced cholangiocarcinoma remains obscure. A previous whole-genome mutation analysis of cholangiocarcinoma of four cases exposed to 1,2-DCP suggested the involvement of activation-induced cytidine deaminase (AID), based on specific signatures of mutation patterns...
November 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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