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Toxicological Sciences: An Official Journal of the Society of Toxicology

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https://read.qxmd.com/read/30869787/corrigendum-to-transient-receptor-potential-ion-channels-mediate-adherens-junctions-dysfunction-in-a-toluene-diisocyanate-induced-murine-asthma-model
#1
(no author information available yet)
No abstract text is available yet for this article.
March 14, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30859219/developmental-dieldrin-exposure-alters-dna-methylation-at-genes-related-to-dopaminergic-neuron-development-and-parkinson-s-disease-in-mouse-midbrain
#2
Joseph Kochmanski, Sarah E VanOeveren, Joseph R Patterson, Alison I Bernstein
Human and animal studies have shown that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson's disease (PD). Despite previous work showing a link between developmental dieldrin exposure and increased neuronal susceptibility to MPTP toxicity in male C57BL/6 mice, the mechanism mediating this effect has not been identified. Here, we tested the hypothesis that developmental exposure to dieldrin increases neuronal susceptibility via genome-wide changes in DNA methylation...
March 11, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30859215/hmgb1-rage-signaling-plays-a-role-in-organic-dust-induced-microglial-activation-and-neuroinflammation
#3
Nyzil Massey, Sreekanth Puttachary, Sanjana Mahadev-Bhat, Anumantha G Kanthasamy, Chandrashekhar Charavaryamath
Occupational exposure to contaminants in agriculture and other industries is known to cause significant respiratory ailments. The effect of organic dust on lung inflammation and tissue remodeling has been actively investigated over many years but the adverse effect of organic dust exposure on the central vital organ brain is beginning to emerge. Brain microglial cells are a major driver of neuroinflammation upon exposure to danger signals. Therefore, we tested a hypothesis that organic dust-exposure of microglial cells induces microglial cell activation and inflammation through HMGB1-RAGE signaling...
March 11, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30859212/simvastatin-inhibits-l-type-ca2-channel-activity-through-impairment-of-mitochondrial-function
#4
Liam Curry, Hani Almukhtar, Jala Alahmed, Richard Roberts, Paul A Smith
Plasma membrane ion channels and mitochondrial electron transport complexes (mETC) are recognised "off-targets" for certain drugs. Simvastatin is one such drug, a lipophilic statin used to treat hypercholesterolaemia, but which is also associated with adverse effects like myopathy and increased risk of glucose intolerance. Such myopathy is thought to arise through adverse actions of simvastatin on skeletal muscle mETC and mitochondrial respiration. In this study we investigated whether the glucose intolerance associated with simvastatin is also mediated via adverse effects on mETC in pancreatic beta-cells since mitochondrial respiration underlies insulin secretion from these cells, an effect in part mediated by promotion of Ca2+ influx via opening of voltage-gated Ca2+ channels (VGCCs)...
March 11, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30859209/targeting-intracellular-calcium-stores-alleviates-neurological-morbidities-in-a-dfp-based-rat-model-of-gulf-war-illness
#5
Kristin F Phillips, Edna Santos, Robert E Blair, Laxmikant S Deshpande
Gulf War Illness (GWI) is a chronic multi-symptom disorder afflicting the veterans of the First Gulf War, and includes neurological symptoms characterized by depression and memory deficits. Chronic exposure to organophosphates (OP) is considered a leading cause for GWI, yet its pathobiology is not fully understood. We recently observed chronic elevations in neuronal Ca2+ levels ([Ca2+]i) in an OP- diisopropyl fluorophosphate (DFP) based rat model for GWI. This study was aimed at identifying mechanisms underlying elevated [Ca2+]i in this DFP model and investigating whether their therapeutic targeting could improve GWI-like neurological morbidities...
March 11, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30856655/erratum-to-screening-for-developmental-neurotoxicity-at-the-national-toxicology-program-the-future-is-here
#6
(no author information available yet)
No abstract text is available yet for this article.
March 11, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30851105/egfr-dependent-il8-production-by-airway-epithelial-cells-after-exposure-to-the-food-flavoring-chemical-2-3-butanedione
#7
F L Kelly, K E Weinberg, A E Nagler, A B Nixon, M D Star, J L Todd, D M Brass, S M Palmer
2,3-butanedione (DA), a component of artificial butter flavoring, is associated with the development of occupational bronchiolitis obliterans (BO), a disease of progressive airway fibrosis resulting in lung function decline. Neutrophilic airway inflammation is a consistent feature of BO across a range of clinical contexts and may contribute to disease pathogenesis. Therefore, we sought to determine the importance of the neutrophil chemotactic cytokine interleukin-8 (IL-8) in DA induced lung disease using in-vivo and in-vitro model systems...
March 9, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30850843/deltamethrin-exposure-daily-from-postnatal-day-3-20-in-sprague-dawley-rats-causes-long-term-cognitive-and-behavioral-deficits
#8
Emily M Pitzer, Chiho Sugimoto, Gary A Gudelsky, Courtney L Huff Adams, Michael T Williams, Charles V Vorhees
Pyrethroids are synthetic insecticides that act acutely on voltage gated sodium channels to prolong channel opening and depolarization. Epidemiological studies find that exposure to pyrethroids are associated with neurological and developmental abnormalities in children. The long-term effects of Type II pyrethroids, such as deltamethrin (DLM), on development have received little attention. We exposed Sprague-Dawley rats to DLM by gavage at doses of 0, 0.25, 0.5, and 1.0 mg/kg/day from postnatal day (P) 3-20 in a split-litter design...
March 8, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30850839/blt-immune-humanized-mice-as-a-model-for-nivolumab-induced-immune-mediated-adverse-events-comparison-of-the-nog-and-nog-exl-strains
#9
James L Weaver, Leah M Zadrozny, Kathleen Gabrielson, Kenrick M Semple, Katherine I Shea, Kristina E Howard
Checkpoint inhibitors represent a new class of therapeutics in the treatment of cancer that have demonstrated remarkable clinical effectiveness. However, some patients have experienced serious immune-mediated adverse effects including pneumonitis, hepatitis, colitis, nephritis, dermatitis, encephalitis, and adrenal or pituitary insufficiency. These adverse events were not predicted by nonclinical studies. To determine if bone marrow-liver-thymus (BLT) immune humanized mice could demonstrate these adverse effects, we studied the effect of nivolumab on two strains of BLT-humanized mice, NOD...
March 8, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30850835/the-power-of-resolution-contextualized-understanding-of-biological-responses-to-liver-injury-chemicals-using-high-throughput-transcriptomics-and-benchmark-concentration-modeling
#10
Sreenivasa C Ramaiahgari, Scott S Auerbach, Trey O Saddler, Julie R Rice, Paul E Dunlap, Nisha S Sipes, Michael J DeVito, Ruchir R Shah, Pierre R Bushel, B Alex Merrick, Richard S Paules, Stephen S Ferguson
Prediction of human response to chemical exposures is a major challenge in both pharmaceutical and toxicological research. Transcriptomics has been a powerful tool to explore chemical-biological interactions, however, limited throughput, high-costs and complexity of transcriptomic interpretations have yielded numerous studies lacking sufficient experimental context for predictive application. To address these challenges, we have utilized a novel high-throughput transcriptomics (HTT) platform, TempO-Seq, to apply the interpretive power of concentration-response modeling with exposures to 24 reference compounds in both differentiated and non-differentiated human HepaRG cell cultures...
March 8, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30843041/maternal-engineered-nanomaterial-inhalation-during-gestation-disrupts-vascular-kisspeptin-reactivity
#11
Elizabeth C Bowdridge, Alaeddin B Abukabda, Kevin J Engles, Carroll R McBride, Thomas P Batchelor, William T Goldsmith, Krista L Garner, Sherri Friend, Timothy R Nurkiewicz
Maternal engineered nanomaterial (ENM) inhalation is associated with uterine vascular impairments and endocrine disruption that may lead to altered gestational outcomes. We have shown that nano-titanium dioxide (nano-TiO2) inhalation impairs endothelium-dependent uterine arteriolar dilation in pregnant rats. However, the mechanism underlying this dysfunction is unknown. Due to its role as a potent vasoconstrictor and essential reproductive hormone, we examined how kisspeptin is involved in nano-TiO2-induced vascular dysfunction and placental efficiency...
March 7, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30835286/novel-brain-penetrating-oxime-acetylcholinesterase-reactivators-attenuate-organophosphate-induced-neuropathology-in-the-rat-hippocampus
#12
Mary B Dail, Charles A Leach, Edward C Meek, Alicia K Olivier, Ronald B Pringle, Carol E Green, Janice E Chambers
Organophosphate (OP) anticholinesterases cause excess acetylcholine leading to seizures which, if prolonged, result in neuronal damage in the rodent brain. Novel substituted phenoxyalkyl pyridinium oximes have previously shown evidence of penetrating the rat blood-brain barrier (BBB) in in vivo tests with a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the active metabolite of the insecticide parathion, paraoxon (PXN), by reducing the time to cessation of seizure-like behaviors and accumulation of glial fibrillary acidic protein, while 2-PAM did not...
March 5, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30835285/the-next-generation-blueprint-of-computational-toxicology-at-the-u-s-environmental-protection-agency
#13
Russell S Thomas, Tina Bahadori, Timothy J Buckley, John Cowden, Chad Deisenroth, Kathie L Dionisio, Jeffrey B Frithsen, Christopher M Grulke, Maureen R Gwinn, Joshua A Harrill, Mark Higuchi, Keith A Houck, Michael F Hughes, E Sidney Hunter, Kristin K Isaacs, Richard S Judson, Thomas B Knudsen, Jason C Lambert, Monica Linnenbrink, Todd M Martin, Seth R Newton, Stephanie Padilla, Grace Patlewicz, Katie Paul-Friedman, Katherine A Phillips, Ann M Richard, Reeder Sams, Timothy J Shafer, R Woodrow Setzer, Imran Shah, Jane E Simmons, Steven O Simmons, Amar Singh, Jon R Sobus, Mark Strynar, Adam Swank, Rogelio Tornero-Valez, Elin M Ulrich, Daniel L Villeneuve, John F Wambaugh, Barbara A Wetmore, Antony J Williams
The U.S. Environmental Protection Agency (EPA) is faced with the challenge of efficiently and credibly evaluating chemical safety often with limited or no available toxicity data. The expanding number of chemicals found in commerce and the environment, coupled with time and resource requirements for traditional toxicity testing and exposure characterization, continue to underscore the need for new approaches. In 2005, EPA charted a new course to address this challenge by embracing computational toxicology (CompTox) and investing in the technologies and capabilities to push the field forward...
March 5, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30830218/safety-concerns-of-diamide-insecticides
#14
János Almássy, László Csernoch, Péter P Nánási
No abstract text is available yet for this article.
March 4, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30830211/tetrabromobisphenol-a-tbbpa-alters-abc-transport-at-the-blood-brain-barrier
#15
R E Cannon, A W Trexler, G A Knudsen, R A Evans, L S Birnbaum
Tetrabromobisphenol A (TBBPA, CAS No. 79-94-7) is a brominated flame retardant (BFR) used in 90% of epoxy coated circuit boards. Exposures to TBBPA can induce neurotoxicity, and disrupt MAPK, estrogen, thyroid, and PPAR-associated signaling pathways [1-5]. Since these pathways also regulate transporters of the central nervous system (CNS) barriers [6-9], we sought to determine the effect of TBBPA on the expression and activity of three ABC transporters of the blood-brain barrier (BBB). Using a confocal based assay, we measured the ex vivo and in vivo effects of TBBPA on P-glycoprotein (P-gp), Breast Cancer Resistant Protein (BCRP), and Multidrug Resistance-associated Protein 2 (MRP2) transport activity in rat brain capillaries...
March 4, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30830166/additional-safety-assessments-needed-for-diamide-insecticides
#16
Isaac N Pessah, Kim Truong
No abstract text is available yet for this article.
March 4, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30825315/nrf2-ameliorates-ddc-induced-sclerosing-cholangitis-and-biliary-fibrosis-and-improves-the-regenerative-capacity-of-the-liver
#17
Athanassios Fragoulis, Julia Schenkel, Miriam Herzog, Tim Schellenberg, Holger Jahr, Thomas Pufe, Christian Trautwein, Thomas W Kensler, Konrad L Streetz, Christoph Jan Wruck
The Nrf2 pathway protects against oxidative stress and induces regeneration of various tissues. Here, we investigated whether Nrf2 protects from sclerosing cholangitis and biliary fibrosis and simultaneously induces liver regeneration. Diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was fed to Nrf2-KO mice (Nrf2-/-), mice with liver-specific hyper-activated Nrf2 (HKeap1-/-) and wild type (WT) littermates to induce cholangitis, liver fibrosis, and oval cell expansion. HKeap1-/--mice were protected from almost all DDC-induced injury compared to WT and Nrf2-/-...
March 2, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30825313/repeatability-and-reproducibility-of-the-rtgill-w1-cell-line-assay-for-predicting-fish-acute-toxicity
#18
Melanie Fischer, Scott E Belanger, Pascale Berckmans, Mary J Bernhard, Ludek Bláha, Diana E Coman Schmid, Scott D Dyer, Tina Haupt, Joop L M Hermens, Maria T Hultman, Heike Laue, Adam Lillicrap, Marie Mlnaříková, Andreas Natsch, Jiří Novák, Theo L Sinnige, Knut Erik Tollefsen, Valentin von Niederhäusern, Hilda Witters, Anze Županič, Kristin Schirmer
Predicting fish acute toxicity of chemicals in vitro is an attractive alternative method to the conventional approach using juvenile and adult fish. The rainbow trout (Oncorhynchus mykiss) cell line assay with RTgill-W1 cells has been designed for this purpose. It quantifies cell viability using fluorescent measurements for metabolic activity, cell- and lysosomal- membrane integrity on the same set of cells. Results from over 70 organic chemicals attest to the high predictive capacity of this test. We here report on the repeatability (intra-laboratory variability) and reproducibility (inter-laboratory variability) of the RTgill-W1 cell line assay in a round-robin study focusing on six test chemicals involving six laboratories from the industrial and academic sector...
March 2, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30825310/sex-modifies-acute-ozone-mediated-airway-physiologic-responses
#19
Anastasiya Birukova, Jaime Cyphert-Daly, R Ian Cumming, Yen-Rei Yu, Kymberly M Gowdy, Loretta G Que, Robert M Tighe
Sex differences clearly exist in incidence, susceptibility, and severity of airway disease and in pulmonary responses to air pollutants such as ozone (O3). Prior rodent O3 exposure studies demonstrate sex-related differences in the expression of lung inflammatory mediators and signaling. However, whether or not sex modifies O3-induced airway physiologic responses remains less explored. To address this, we exposed 8-10 week old male and female C57BL/6 mice to either 1 or 2 ppm O3 or filtered air (FA) for 3 h...
March 2, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30816951/evaluation-of-chemical-effects-on-network-formation-in-cortical-neurons-grown-on-microelectrode-arrays
#20
Timothy J Shafer, Jasmine P Brown, Brittany Lynch, Sylmarie Davila-Montero, Kathleen Wallace, Katie Paul Friedman
Thousands of chemicals to which humans are potentially exposed have not been evaluated for potential developmental neurotoxicity (DNT), driving efforts to develop a battery of in vitro screening approaches for DNT hazard. Here, 136 unique chemicals were evaluated for potential DNT hazard using a network formation assay (NFA) in cortical cells grown on microelectrode arrays (MEAs). The effects of chemical exposure from 2 hr post-plating through 12 days in vitro (DIV) on network formation were evaluated at DIV 5, 7, 9 and 12, with cell viability assessed at DIV 12...
February 28, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
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