journal
MENU ▼
Read by QxMD icon Read
search

Toxicological Sciences: An Official Journal of the Society of Toxicology

journal
https://www.readbyqxmd.com/read/29432603/in-vitro-screening-for-seizure-liability-using-microelectrode-array-technology
#1
Jenifer A Bradley, Harry H Luithardt, Monica R Metea, Christopher J Strock
Drug induced seizure liabilities produce significant compound attrition during drug discovery. Currently available in vitro cytotoxicity assays cannot predict all toxicity mechanisms due to the failure of these assays to predict sublethal target specific electrophysiological liabilities. Identification of seizurogenic and other electrophysiological effects at early stages of the drug development process is important to ensure that safe candidate compounds can be developed while chemical design is taking place, long before these liabilities are discovered in costly preclinical in vivo studies...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29432567/bile-acid-sequestration-by-cholestyramine-mitigates-fgfr4-inhibition-induced-alt-elevation
#2
Heiko S Schadt, Armin Wolf, Joerg Andreas Mahl, Kuno Wuersch, Philippe Couttet, Marianne Schwald, Audrey Fischer, Mathilde Lienard, Corinne Emotte, Chi-Hse Teng, Elizabeth Skuba, Terrilyn A Richardson, Luigi Manenti, Andreas Weiss, Diana Graus Porta, Robin A Fairhurst, Gerd A Kullak-Ublick, Salah-Dine Chibout, Francois Pognan, William Kluwe, Jacqueline Kinyamu-Akunda
The FGF19-FGFR4-βKlotho (KLB) pathway plays an important role in the regulation of bile acid (BA) homeostasis. Aberrant activation of this pathway has been described in the development and progression of a subset of liver cancers including hepatocellular carcinoma (HCC), establishing FGFR4 as an attractive therapeutic target for such solid tumors. FGF401 is a highly selective FGFR4 kinase inhibitor being developed for HCC, currently in Phase I/II clinical studies. In preclinical studies in mice and dogs, oral administration of FGF401 led to induction of Cyp7a1, elevation of its peripheral marker 7alpha-hydroxy-4-cholesten-3-one (C4), increased BA pool size, decreased serum cholesterol and diarrhea in dogs...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29420809/unexpected-effects-of-propiconazole-tebuconazole-and-their-mixture-on-the-receptors-car-and-pxr-in-human-liver-cells
#3
Constanze Knebel, Jannika Neeb, Elisabeth Zahn, Flavia Schmidt, Alejandro Carazo, Ondej Holas, Petr Pavek, Gerhard P Püschel, Ulrich M Zanger, Roderich Süssmuth, Alfonso Lampen, Philip Marx-Stoelting, Albert Braeuning
Analyzing mixture toxicity requires an in-depth understanding of the mechanisms of action of its individual components. Substances with the same target organ, same toxic effect and same mode of action are believed to cause additive effects, whereas substances with different modes of action are assumed to act independently. Here, we tested two triazole fungicides, propiconazole and tebuconazole, for individual and combined effects on liver toxicity-related endpoints. Both triazoles are proposed to belong to the same cumulative assessment group (CAG) and are therefore thought to display similar and additive behavior...
February 6, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29409050/shp-deficiency-increases-inflammatory-liver-injury-through-cxcl2-driven-neutrophil-recruitment-in-mice
#4
Jung-Ran Noh, Yong-Hoon Kim, Don-Kyu Kim, Jung Hwan Hwang, Kyoung-Shim Kim, Dong-Hee Choi, Seon-Jin Lee, Hee Gu Lee, Tae Geol Lee, Hong-Lei Weng, Steven Dooley, Hueng-Sik Choi, Chul-Ho Lee
Although detailed pathophysiological mechanisms of fulminant hepatitis remain elusive, immune cell recruitment with excessive cytokine production is a well-recognized hallmark of the disease. We determined the function of orphan nuclear receptor small heterodimer partner (SHP) in concanavalin A (ConA)-induced hepatitis model. Male C57BL/6J mice were injected intravenously with either a lethal dose (25 mg/kg) or a sub-lethal dose (15 mg/kg) of ConA. For the C-X-C motif chemokine ligand (CXCL) 2 neutralization study, mice were intravenously administered anti-mouse CXCL2 antibody (100 μg/mouse)...
February 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29409039/the-affinity-of-brominated-phenolic-compounds-for-human-and-zebrafish-thyroid-receptor-%C3%AE-influence-of-chemical-structure
#5
Erin M Kollitz, Lauren De Carbonnel, Heather M Stapleton, P Lee Ferguson
Brominated phenolic compound (BPCs) are found in the environment, and in human and wildlife tissues, and some are considered to have endocrine disrupting activities. The goal of this study was to determine how structural differences of three BPC classes impact binding affinities for the thyroid receptor beta (TRβ) in humans and zebrafish. BPC classes included halogenated bisphenol A (BPA) derivatives, halogenated oxidative transformation products of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), and brominated phenols...
February 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29409005/environmental-and-dietary-exposure-to-copper-and-its-cellular-mechanisms-linking-to-alzheimer-disease
#6
Heng-Wei Hsu, Stephen C Bondy, Masashi Kitazawa
Metals are commonly found in the environment, household, and workplaces in various forms, and a significant segment of the population is routinely exposed to the trace amount of metals from variety of sources. Exposure to metals, such as aluminum, lead, iron, and copper, from environment has long been debated as a potential environmental risk factor for Alzheimer's disease (AD) for decades, yet results from in vitro, in vivo, and human population remain controversial. In the case of copper, the neurotoxic mechanism of action was classically viewed as its strong affinity to amyloid-beta (Aβ) to help its aggregation and increase oxidative stress via Fenton reaction...
February 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29394417/association-analysis-identifies-new-risk-loci-for-coal-workers-pneumoconiosis-in-han-chinese-men
#7
Ting Wang, Yan Li, Meng Zhu, Wenxi Yao, Hongyan Wu, Xiaoming Ji, Zhibin Hu, Hongbing Shen, Xiangshan Fan, Chunhui Ni
Coal worker's pneumoconiosis (CWP) is a debilitating and progressive occupational lung disease resulted from long-term inhalation of airborne silica-containing coal mine dust. Both environmental factors and genetic variations contribute to CWP. Our previous genome-wide association study (GWAS) revealed a tiny fraction of variants with the top associations in Chinese Han population. To identify novel susceptibility loci of CWP, functional variants with suboptimal associations in the GWAS scan were further studied here...
January 31, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29394414/ultrafine-particulate-matter-combined-with-ozone-exacerbates-lung-injury-in-mature-adult-rats-with-cardiovascular-disease
#8
Emily M Wong, William F Walby, Dennis W Wilson, Fern Tablin, Edward S Schelegle
BACKGROUND: Particulate matter (PM) and ozone (O3) are dominant air pollutants that contribute to development and exacerbation of multiple cardiopulmonary diseases. Mature adults with cardiovascular disease (CVD) are particularly susceptible to air pollution-related cardiopulmonary morbidities and mortalities. OBJECTIVES: The aim was to investigate the biologic potency of ultrafine particulate matter (UFPM) combined with O3 in the lungs of mature adult normotensive and spontaneously hypertensive Wistar-Kyoto rats...
January 31, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385630/placental-lncrna-expression-is-associated-with-prenatal-phthalate-exposure
#9
Ronit Machtinger, Jia Zhong, Abdallah Mansur, Michal Adir, Catherine Racowsky, Russ Hauser, Kasey Brennan, Oskar Karlsson, Andrea A Baccarelli
Phthalates are endocrine disrupting chemicals (EDCs) that can cross the placenta and affect the fetal epigenome. Among various epigenetic regulators of gene expression, long non-coding RNAs (lncRNAs) are important players that may also be involved in the manifestation of EDC toxicity. We sought to explore the association between maternal urinary phthalate metabolite concentrations and lncRNA expression in human placenta to better understand potential mechanisms through which lncRNAs participate in mediating phthalate toxicity...
January 29, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385629/exposure-to-dbp-and-high-iodine-aggravates-autoimmune-thyroid-disease-through-increasing-the-levels-of-il-17-and-thyroid-binding-globulin-in-wistar-rats
#10
Jiufei Duan, Jun Kang, Ting Deng, Xu Yang, Mingqing Chen
Autoimmune thyroid disease (AITD) is the most common autoimmune disease that causes hypothyroidism. High iodine is a well-known factor that can induce thyroid disorders, including Hashimoto's thyroiditis, one of the main types of AITD. Recent epidemiological studies have indicated that phthalates, especially di-n-butyl phthalate (DBP) may induce thyroid disease. In this study, we aim to determine the effects and underlying mechanisms of high iodine and/or DBP exposure on AITD. Female Wistar rats were modeled with thyroglobulin and exposed to high iodine and/or DBP...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385628/evaluating-in-vitro-in-vivo-extrapolation-of-toxicokinetics
#11
John F Wambaugh, Michael F Hughes, Caroline L Ring, Denise K MacMillan, Jermaine Ford, Timothy R Fennell, Sherry R Black, Rodney W Snyder, Nisha S Sipes, Barbara Wetmore, Joost Westerhout, R Woodrow Setzer, Robert Pearce, Jane-Ellen Simmons, Russell S Thomas
Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental-relevance...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385627/mechanisms-underlying-aluminium-neurotoxicity-related-to-14-3-3%C3%AE-protein
#12
Xiaomei Wang, Dai Cheng, Weibo Jiang, Yuxia Ma
Studies have shown aluminium (Al) is associated with Alzheimer's disease (AD) causality, however, the mechanism underlying this link remains unclear. To investigate the Al neurotoxicity, the high Al-affinity protein from pig hippocampus was screened by native gel electrophoresis and Al3+ plus 8-hydroxyquinoline (8-HQ) staining. The protein with high Al3+-affinity was identified to be 14-3-3ζ, which was then used for raising antibodies. By 8-HQ staining and immunocytochemical localization, we found the co-location of Al3+ and 14-3-3ζ increased markedly in the Al-exposed rat hippocampus tissue and the cultured rat primary hippocampal neuronal cells...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385626/developmental-thyroid-hormone-insufficiency-induces-a-cortical-brain-malformation-and-learning-impairments-a-cross-fostering-study
#13
K O'Shaughnessy, P Kosian, J Ford, W Oshiro, S Degitz, M E Gilbert
Thyroid hormones (TH) are essential for brain development, but there exists few rodent models that link TH insufficiency to apical neurodevelopmental endpoints. We have previously described a structural anomaly, a heterotopia, in the brains of rats treated in utero with propylthiouracil (PTU). However, how the timing of an exposure relates to this birth defect is unknown. This study seeks to understand how various temporal treatments of the mother relates to TH insufficiency and adverse neurodevelopment of the offspring...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385624/comparative-genotoxicity-of-tempo-and-three-of-its-derivatives-in-mouse-lymphoma-cells
#14
Xiaoqing Guo, Ji-Eun Seo, Steven M Bryce, Jenna A Tan, Qiangen Wu, Stacey L Dial, M Moore Martha, Nan Mei
TEMPO and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In the present study, we investigated and quantified the genotoxicity of four structurally similar nitroxides, TEMPO and three of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385596/optimized-methods-to-explore-the-mechanistic-and-biomarker-potential-of-hepatocyte-derived-exosomes-in-drug-induced-liver-injury
#15
Sarah E Thacker, Manisha Nautiyal, Monicah A Otieno, Paul B Watkins, Merrie Mosedale
Recent evidence supports that alterations in hepatocyte-derived exosomes (HDE) may play a role in the pathogenesis of drug-induced liver injury (DILI). HDE-based biomarkers also hold promise to improve the sensitivity of existing in vitro assays for predicting DILI liability. Primary human hepatocytes (PHH) provide a physiologically relevant in vitro model to explore the mechanistic and biomarker potential of HDE in DILI. However, optimal methods to study exosomes in this culture system have not been defined...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385576/aging-exacerbates-neuroinflammatory-outcomes-induced-by-acute-ozone-exposure
#16
Christina R Tyler, Shahani Noor, Tamara Young, Valeria Rivero, Bethany Sanchez, Selita Lucas, Kevin K Caldwell, Erin D Milligan, Matthew J Campen
The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12 - 18 months were exposed to either filtered air (FA) or 1.0 ppm O3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385573/challenges-associated-with-applying-physiologically-based-pharmacokinetic-modeling-for-public-health-decision-making
#17
Yu-Mei Tan, Rachel Worley, Jeremy A Leonard, Jeffrey Fisher
The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology has grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has thus far occurred for only a few environmental chemicals. In order to encourage decision makers to embrace the critical role of PBPK modeling in risk assessment, several important challenges require immediate attention from the modeling community...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385569/dronedarone-induced-cardiac-mitochondrial-dysfunction-and-its-mitigation-by-epoxyeicosatrienoic-acids
#18
Aneesh Karkhanis, Jacqueline Wen Hui Leow, Thilo Hagen, Eric Chun Yong Chan
Dronedarone and amiodarone are structurally similar antiarrhythmic drugs. Dronedarone worsens cardiac adverse effects with unknown causes while amiodarone has no cardiac adversity. Dronedarone induces preclinical mitochondrial toxicity in rat liver and exhibits clinical hepatotoxicity. Here, we further investigated the relative potential of the antiarrhythmic drugs in causing mitochondrial injury in cardiomyocytes. Differentiated rat H9c2 cardiomyocytes were treated with dronedarone, amiodarone and their respective metabolites namely N-desbutyldronedarone (NDBD) and N-desethylamiodarone (NDEA)...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29385562/expression-profiling-of-human-pluripotent-stem-cell-derived-cardiomyocytes-exposed-to-doxorubicin-integration-and-visualization-of-multi-omics-data
#19
Gustav Holmgren, Peter Sartipy, Christian X Andersson, Anders Lindahl, Jane Synnergren
Anthracyclines, such as doxorubicin, are highly efficient chemotherapeutic agents against a variety of cancers. However, anthracyclines are also among the most cardiotoxic therapeutic drugs presently on the market. Chemotherapeutic-induced cardiomyopathy is one of the leading causes of disease and mortality in cancer survivors. The exact mechanisms responsible for doxorubicin-induced cardiomyopathy are not completely known, but the fact that the cardiotoxicity is dose-dependent and that there is a variation in time-to-onset of toxicity, and gender- and age differences suggests that several mechanisms may be involved...
January 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29361160/glutathione-s-transferase-protein-expression-in-different-life-stages-of-zebrafish-danio-rerio
#20
Alena Tierbach, Ksenia J Groh, René Schönenberger, Kristin Schirmer, Marc J-F Suter
Zebrafish is a widely used animal model in biomedical sciences and toxicology. Although evidence for the presence of phase I and phase II xenobiotic defense mechanisms in zebrafish exists on the transcriptional and enzyme activity level, little is known about the protein expression of xenobiotic metabolizing enzymes. Given the important role of glutathione S-transferases (GSTs) in phase II biotransformation, we analyzed cytosolic GST proteins in zebrafish early life stages and different organs of adult male and female fish, using a targeted proteomics approach...
January 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
journal
journal
32959
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"