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Toxicological Sciences: An Official Journal of the Society of Toxicology

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https://www.readbyqxmd.com/read/28666365/chronic-low-dose-cadmium-exposure-impairs-cutaneous-wound-healing-with-defective-early-inflammatory-responses-after-skin-injury
#1
Hong Mei, Pengle Yao, Shanshan Wang, Na Li, Tengfei Zhu, Xiaofang Chen, Mengmei Yang, Shu Zhuo, Shiting Chen, Ji Ming Wang, Hui Wang, Dong Xie, Yongning Wu, Yingying Le
Impairment of the immune system is a developing concern in evaluating the toxicity of Cadmium (Cd). In the present study, we investigated if Cd could impair cutaneous wound healing through interfering with inflammation after injury. We found that exposure of mice to CdCl2 through drinking water at doses of 10, 30 and 50 mg/L for 8 weeks significantly impaired cutaneous wound healing. Chronic 30 mg/L CdCl2 treatment elevated murine blood Cd level comparable to that of low dose Cd-exposed humans, had no effect on blood total and differential leukocyte counts, but reduced neutrophil infiltration, chemokines (CXCL1, CXCL2) and proinflammatory cytokines (TNFα, IL-1β, and IL-6) expression in wounded tissue at early stage after injury...
June 29, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28666384/gut-microbial-transformation-of-the-dietary-imidazoquinoxaline-mutagen-meiqx-reduces-its-cytotoxic-and-mutagenic-potency
#2
Jianbo Zhang, Michael T Empl, Clarissa Schwab, Mostafa I Fekry, Christina Engels, Mirjam Schneider, Christophe Lacroix, Pablo Steinberg, Shana J Sturla
The diverse community of microbes present in the human gut has emerged as an important factor for cancer risk, potentially by altering exposure to chemical carcinogens. In the present study, human gut bacteria were tested for their capacity to transform the carcinogenic heterocyclic amine 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Eubacterium hallii, Lactobacillus reuteri, and Lactobacillus rossiae were able to convert MeIQx to a new microbial metabolite characterized on the basis of high resolution mass spectrometry and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2',1':2,3]imidazo[4,5-f]quinoxaline (MeIQx-M1), resulting from conjugation with activated glycerol...
June 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28666377/a-mechanistic-model-for-predicting-lung-inflammogenicity-of-oxide-nanoparticles
#3
Enrico Burello
This study presents a mechanistic model for identifying oxide nanoparticles that induce a high level of neutrophils in the bronchoalveolar lavage fluid, an important marker for lung inflammogenicity. The model is based on 4 nanoparticles' physicochemical properties, i.e. the reactivity, surface charge, wettability, and dissolution.First, I calculate these properties and show that theoretical values reproduce acceptably the experimental measurements. Then, I combine these properties with mechanistic knowledge to build a classification model for the prediction of acute in vivo lung inflammogenicity, measured as the total number of polymorphonuclear neutrophils...
June 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28666375/role-of-peptide-yy3-36-and-glucose-dependent-insulinotropic-polypeptide-in-anorexia-induction-by-trichothecences-t-2-toxin-ht-2-toxin-diacetoxyscirpenol-and-neosolaniol
#4
Jie Zhang, Hui Jia, Qingqing Wang, Yajie Zhang, Wenda Wu, Haibin Zhang
Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS) and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma...
June 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28666357/permitted-daily-exposure-pde-of-the-androgen-receptor-antagonist-flutamide
#5
Lefteris C Zacharia
This report aims to determine the Permitted Daily Exposure (PDE) of flutamide, an androgen receptor blocker, as directed by guideline EMA/CHMP/CVPM/SWP/169430/2012 that came into effect on June 2015. A literature review was conducted to identify toxicity studies of flutamide. Hazards and sensitive endpoints were determined. Based on the No Adverse effect Level (NOAELs) and Lowest Observed Adverse effect Levels (LOAELs) reported from both reproductive, developmental and 28 day toxicity studies the PDE was calculated...
June 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28645175/perturbation-to-cholesterol-at-the-neuromuscular-junction-confers-botulinum-neurotoxin-a-sensitivity-to-neonatal-mice
#6
Baskaran Thyagarajan, Joseph G Potian, Joseph J McArdle, Padmamalini Baskaran
Botulinum neurotoxin A (BoNT/A) cleaves SNAP25 at the motor nerve terminals (MNT) and inhibits stimulus evoked acetylcholine release (SEAR). This causes skeletal muscle paralysis. However, younger neonatal mice (<P7; less than 7 days old) are resistant to the neuroparalytic effects of BoNT/A. That is, in vivo injection of BoNT/A at the innervations of Extensor digitorum longus (EDL) muscle in the hindlimbs inhibited the toe spread reflex within 24 hours following BoNT/A injection in adult mouse and in older (> P7) neonatal mice younger than 7 days-age remained unaffected by BoNT/A injection...
June 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28633506/role-of-glucagon-like-peptide-1and-gastric-inhibitory-peptide-in-anorexia-induction-following-oral-exposure-to-the-trichothecene-mycotoxin-deoxynivalenol-vomitoxin
#7
Hui Jia, Wen-Da Wu, Xi Lu, Jie Zhang, Cheng-Hua He, Hai-Bin Zhang
Deoxynivalenol (DON), which is a Type B trichothecene mycotoxin produced by Fusarium, frequently contaminates cereal staples, such as wheat, barley and corn. DON threatens animal and human health by suppressing food intake and impairing growth. While anorexia induction in mice exposed to DON has been linked to the elevation of the satiety hormones cholecystokinin (CCK) and peptide YY3-36(PYY3-36) in plasma, the effects of DON on the release of other satiety hormones, such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), have not been established...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28633499/lateralized-basal-ganglia-vulnerability-to-pesticide-exposure-in-asymptomatic-agricultural-workers
#8
Mechelle M Lewis, Nicholas W Sterling, Guangwei Du, Eun-Young Lee, Grace Shyu, Michael Goldenberg, Thomas Allen, Christy Stetter, Lan Kong, Shedra Amy Snipes, Byron C Jones, Honglei Chen, Richard B Mailman, Xuemei Huang
Background: Pesticide exposure is linked to Parkinson's disease (PD), a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticide-exposed agricultural workers (AW) have nigral diffusion tensor (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28633468/skin-sensitization-challenging-the-conventional-thinking-a-case-against-2-out-of-3-as-integrated-testing-strategy
#9
Henrik Johansson, Robin Gradin
No abstract text is available yet for this article.
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28637328/diesel-engine-exhaust-basis-for-occupational-exposure-limit-value
#10
Piia Taxell, Tiina Santonen
Diesel engines are widely used in transport and power supply, making occupational exposure to diesel exhaust common. Both human and animal studies associate exposure to diesel exhaust with inflammatory lung effects, cardiovascular effects, and an increased risk of lung cancer. The International Agency for Research on Cancer (IARC) has evaluated diesel exhaust as carcinogenic to humans. Yet national or regional limit values for controlling occupational exposure to diesel exhaust are rare. In recent decades, stricter emission regulations have led to diesel technologies evolving significantly, resulting in changes in exhaust emissions and composition...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#11
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28633413/erratum
#12
(no author information available yet)
No abstract text is available yet for this article.
June 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28591870/transcriptome-profiling-reveals-bisphenol-a-alternatives-activate-estrogen-receptor-alpha-in-human-breast-cancer-cells
#13
Robin Mesnage, Alexia Phedonos, Matthew Arno, Sucharitha Balu, J Christopher Corton, Michael N Antoniou
Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in "BPA-free" products. We have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines. Estrogenicity was assessed (10-11M to 10-4M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay...
June 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28541575/xenobiotic-car-activators-induce-dlk1-dio3-locus-non-coding-rna-expression-in-mouse-liver
#14
Lucie Pouché, Antonio Vitobello, Michael Römer, Milica Glogovac, A Kenneth MacLeod, Heidrun Ellinger-Ziegelbauer, Magdalena Westphal, Valérie Dubost, Daniel Philipp Stiehl, Bérengère Dumotier, Alexander Fekete, Pierre Moulin, Andreas Zell, Michael Schwarz, Rita Moreno, Jeffrey T J Huang, Cliff R Elcombe, Colin J Henderson, C Roland Wolf, Jonathan G Moggs, Rémi Terranova
Derisking xenobiotic-induced non-genotoxic carcinogenesis (NGC) represents a significant challenge during the safety assessment of chemicals and therapeutic drugs. The identification of robust mechanism-based NGC biomarkers has the potential to enhance cancer hazard identification. We previously demonstrated Constitutive Androstane Receptor (CAR) and WNT signaling-dependent up-regulation of the pluripotency associated Dlk1-Dio3 imprinted gene cluster non-coding RNAs (ncRNAs) in the liver of mice treated with tumor-promoting doses of phenobarbital (PB)...
May 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28541489/respiratory-effects-and-systemic-stress-response-following-acute-acrolein-inhalation-in-rats
#15
Samantha J Snow, Marie A McGee, Andres Henriquez, Judy E Richards, Mette C Schladweiler, Allen D Ledbetter, Urmila P Kodavanti
Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models. We examined respiratory and systemic effects following exposure to a sensory irritant acrolein to elucidate the systemic and pulmonary consequences in healthy and diabetic rat models. Male Wistar and Goto Kakizaki (GK) rats, a non-obese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4h/day for 1 or 2 days...
May 24, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28535311/quantification-of-estradiol-uptake-in-zebrafish-embryos-and-larvae
#16
J Paige Souder, Daniel A Gorelick
Zebrafish are a powerful model system to assess the molecular and cellular effects of exposure to toxic chemicals during embryonic development. To study the effects of environmental endocrine disruptors, embryos and larvae are commonly exposed to supraphysiologic concentrations of these compounds in the water, but their bioavailability in zebrafish is largely unknown. One hypothesis is that supraphysiologic concentrations of estrogens in the water are required to achieve physiologic levels in vivo, however this has not been directly tested...
May 23, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28525648/the-role-of-omics-in-the-application-of-adverse-outcome-pathways-for-chemical-risk-assessment
#17
Erica K Brockmeier, Geoff Hodges, Thomas H Hutchinson, Emma Butler, Markus Hecker, Knut Erik Tollefsen, Natalia Garcia-Reyero, Peter Kille, Dörthe Becker, Kevin Chipman, John Colbourne, Timothy W Collette, Andrew Cossins, Mark Cronin, Peter Graystock, Steve Gutsell, Dries Knapen, Ioanna Katsiadaki, Anke Lange, Stuart Marshall, Stewart F Owen, Edward J Perkins, Stewart Plaistow, Anthony Schroeder, Daisy Taylor, Mark Viant, Gerald Ankley, Francesco Falciani
In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (UK) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (e.g., transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28525647/evaluation-of-the-effects-of-tanezumab-a-monoclonal-antibody-against-nerve-growth-factor-on-the-sympathetic-nervous-system-in-adult-cynomolgus-monkeys-macaca-fascicularis-a-stereologic-histomorphologic-and-cardiofunctional-assessment
#18
Patrice Belanger, Paul Butler, Mark Butt, Siddhartha Bhatt, Stephen Foote, David Shelton, Mark Evans, Rosalinda Arends, Susan Hurst, Carlin Okerberg, Thomas Cummings, David Potter, Jill Steidl-Nichols, Mark Zorbas
Tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. Three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (SNS) of adult nonhuman primates. Study 1 evaluated potential effects of subcutaneous (SC) tanezumab (1.2 mg/kg every 8 weeks [Q8W]) on SNS in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a non-dosing/recovery period...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#19
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28525602/aloin-a-component-of-the-aloe-vera-plant-leaf-induces-pathological-changes-and-modulates-the-composition-of-microbiota-in-the-large-intestine-of-f344-n-male-rats
#20
Mary D Boudreau, Greg R Olson, Volodymyr P Tryndyak, Matthew S Bryant, Robert P Felton, Frederick A Beland
In a previous study, the oral administration of an Aloe vera whole leaf extract induced dose-related mucosal and goblet cell hyperplasia in the rat colon after 13-weeks and colon cancer after two years. The primary goal of this study was to determine whether or not the administration of aloin, a component of the Aloe vera plant leaf, would replicate the pathophysiological effects that were observed in rats in the previous study with an Aloe vera whole leaf extract. Groups of 10 male F344/N rats were administered aloin at 0, 6...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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