journal
MENU ▼
Read by QxMD icon Read
search

Toxicological Sciences: An Official Journal of the Society of Toxicology

journal
https://www.readbyqxmd.com/read/30329139/all-trans-retinoic-acid-disrupts-development-in-ex-vivo-cultured-fetal-rat-testes-i-altered-seminiferous-cord-maturation-and-testicular-cell-fate
#1
Daniel J Spade, Edward Dere, Susan J Hall, Christoph Schorl, Richard N Freiman, Kim Boekelheide
Exposure to excess retinoic acid disrupts the development of the mammalian testicular seminiferous cord. However, the molecular events surrounding retinoic acid-driven loss of cord structure have not previously been examined. To investigate the mechanisms associated with this adverse developmental effect, fetal rat testes were isolated on gestational day 15, after testis determination and the initiation of cord development, and cultured in media containing all-trans retinoic acid (ATRA; 10-8 to 10-6 M) or vehicle for 3 days...
October 17, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30329129/comparison-of-chlorantraniliprole-and-flubendiamide-activity-towards-wild-type-and-malignant-hyperthermia-susceptible-ryanodine-receptors-and-heat-stress-intolerance
#2
Kim M Truong, Isaac N Pessah
Chlorantraniliprole (CP) and flubendiamide (FD) are widely used in agriculture globally to control lepidopteran pests. Both insecticides target ryanodine receptors (RyRs) and promote Ca2+ leak from sarcoplasmic reticulum (SR) within insect skeletal muscle yet are purportedly devoid of activity towards mammalian RyR1 and muscle. RyRs are ion channels that regulate intracellular Ca2+ release from SR during physiological excitation-contraction coupling. Mutations in RYR1 genes confer malignant hyperthermia susceptibility (MHS), a potentially lethal pharmacogenetic disorder in humans and animals...
October 17, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30321427/proteomic-and-metabolomic-profiling-identify-plasma-biomarkers-for-exposure-to-ultra-low-levels-of-carfentanil
#3
Elizabeth S Dhummakupt, Gabrielle M Rizzo, Michael Feasel, Phillip M Mach, Bao Q Tran, Daniel O Carmany, Paul S Demond, Ethan M McBride, Michele Maughan, Jennifer W Sekowski, Trevor Glaros
Despite the recent epidemic of fentanyl abuse, there are few validated assays capable of rapidly detecting these compounds. In order to improve the ability to detect carfentanil at physiologically relevant concentrations, we developed a systems biology approach to discover host-based markers which are specifically amplified upon exposure in a rabbit model. For this work, two 'omics' pipelines utilizing mass spectrometry were developed and leveraged. First, a proteomics pipeline was developed to interrogate the blood plasma for protein-based biomarkers...
October 13, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30321412/developmental-regulation-of-nuclear-factor-erythroid-2-related-factors-nrfs-by-ahr1b-in-zebrafish-danio-rerio
#4
Alexandra Ulin, Jake Henderson, Minh-Tam Pham, James Meyo, Yuying Chen, Sibel I Karchner, Jared V Goldstone, Mark E Hahn, Larissa M Williams
Interactions between regulatory pathways allow organisms to adapt to their environment and respond to stress. One interaction that has been recently identified occurs between the aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid-2 related factor (NRF) family. Each transcription factor regulates numerous downstream genes involved in the cellular response to toxicants and oxidative stress; they are also implicated in normal developmental pathways. The zebrafish model was used to explore the role of AHR regulation of nrf genes during development and in response to toxicant exposure...
October 13, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30321397/application-of-benchmark-concentration-bmc-analysis-on-zebrafish-data-a-new-perspective-for-quantifying-toxicity-in-alternative-animal-models
#5
Jui-Hua Hsieh, Kristen Ryan, Alexander Sedykh, Ja-An Lin, Andrew J Shapiro, Frederick Parham, Mamta Behl
Over the past decade, the zebrafish is increasingly being used as a model to screen for chemical-mediated toxicities including developmental toxicity (DT) and neurotoxicity (NT). One of the major challenges is lack of harmonization in data analysis approaches, thereby posing difficulty in comparing findings across laboratories. To address this, we sought to establish a unified data analysis strategy for both DT and NT data, by adopting the benchmark concentration (BMC) analysis. There are two critical aspects in the BMC analysis: having a toxicity endpoint amenable for BMC and selecting a proper benchmark response (BMR) for the endpoint...
October 13, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30321396/host-developmental-toxicity-of-bpa-and-bpa-alternatives-is-inversely-related-to-microbiota-disruption-in-zebrafish
#6
Tara R Catron, Scott P Keely, Nichole E Brinkman, Todd J Zurlinden, Charles E Wood, Justin R Wright, Drake Phelps, Emily Anneken Wheaton, Allison Kvasnicka, Shaza Gaballah, Regina Lamendella, Tamara Tal
Host-associated microbiota can biotransform xenobiotics, mediate health effects of chemical exposure, and play important roles in early development. Bisphenol A (BPA) is a widespread environmental chemical that has been associated with adverse endocrine and neurodevelopmental effects, some of which may be mediated by microbiota. Growing public concern over the safety of BPA has resulted in its replacement with structurally similar alternatives. In this study, we evaluated whether BPA and BPA alternatives alter microbiota and modulate secondary adverse behavioral effects in zebrafish...
October 13, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30304530/oxygen-and-arsenite-synergize-phosphine-toxicity-by-distinct-mechanisms
#7
Saad Alzahrani, Paul R Ebert
Phosphine is the only fumigant approved globally for general use to control insect pests in stored grain. Due to the emergence of resistance among insect pests and the lack of suitable alternative fumigants, we are investigating ways to synergistically enhance phosphine toxicity, by studying the mechanism of action of known synergists, such as oxygen, temperature, and arsenite. Under normoxia, exposure of the model organism C. elegans for 24 hours at 20 °C to 70 ppm phosphine resulted in 10% mortality, but nearly 100% mortality if the oxygen concentration was increased to 80%...
October 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30295906/automated-morphological-feature-assessment-for-zebrafish-embryo-developmental-toxicity-screens
#8
Elisabet Teixidó, Tobias R Kießling, Eckart Krupp, Celia Quevedo, Arantza Muriana, Stefan Scholz
Detection of developmental phenotypes in zebrafish embryos typically involves a visual assessment and scoring of morphological features by an individual researcher. Subjective scoring could impact results and be of particular concern when phenotypic effect patterns are also used as a diagnostic tool to classify compounds. Here we introduce a quantitative morphometric approach based on image analysis of zebrafish embryos. A software called FishInspector was developed to detect morphological features from images collected using an automated system to position zebrafish embryos...
October 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30295897/prenatal-bisphenol-a-exposure-alters-epithelial-cell-composition-in-the-rhesus-macaque-fetal-oviduct
#9
Pei-Hsuan Hung, Laura S Van Winkle, Carmen J Williams, Patricia A Hunt, Catherine A VandeVoort
Bisphenol A (BPA) is an endocrine disrupting compound that is a pervasive environmental contaminant. Although it has been reported to affect the development of a variety of fetal reproductive tissues, data on the effect of fetal BPA exposure on oviducts were extremely limited and were only available in mice. To determine if there are adverse effects of gestational BPA exposure on fetal oviduct, we exposed pregnant rhesus macaques with female fetuses to oral or non-oral BPA during the last trimester of gestation (day 100 to term)...
October 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30289550/quantitative-systems-toxicology-analysis-of-in-vitro-mechanistic-assays-reveals-importance-of-bile-acid-accumulation-and-mitochondrial-dysfunction-in-tak-875-induced-liver-injury
#10
Diane M Longo, Jeffrey L Woodhead, Paul Walker, Krisztina Herédi-Szabó, Károly Mogyorósi, Francis S Wolenski, Yvonne P Dragan, Merrie Mosedale, Scott Q Siler, Paul B Watkins, Brett A Howell
TAK-875 (fasiglifam), a GPR40 agonist in development for the treatment of type 2 diabetes (T2D), was voluntarily terminated in Phase III trials due to adverse liver effects. The potential mechanisms of TAK-875 toxicity were explored by combining in vitro experiments with quantitative systems toxicology (QST) using DILIsym®, a mathematical representation of drug-induced liver injury. In vitro assays revealed that bile acid transporters were inhibited by both TAK-875 and its metabolite, TAK-875-Glu. Experimental data indicated that human bile salt export pump (BSEP) inhibition by TAK-875 was mixed while sodium taurocholate co-transporting polypeptide (NTCP) inhibition by TAK-875 was competitive...
October 5, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30289508/the-linc00152-controls-cell-cycle-progression-by-regulating-ccnd1-in-16hbe-cells-malignantly-transformed-by-cigarette-smoke-extract
#11
Zhenzhong Liu, Liu Anfei, Aruo Nan, Ying Cheng, Ti Yang, Xin Dai, Lijian Chen, Xin Li, Yangyang Jia, Nan Zhang, Yiguo Jiang
Smoking is one of the major environmental risk factors for lung cancer. In recent years, the role of long-chain non-coding RNAs (lncRNA) in chemical carcinogenesis has attracted extensive research attention. In this study, we treated human bronchial epithelial cells with cigarette smoke extract (CSE) at a dose of 2 μg/mL to establish a malignantly transformed cellular model (16HBE-M). Screening of lncRNAs highly expressed in transformed cells via differential analysis revealed a crucial role of linc00152 in CSE-induced malignant transformation...
October 5, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30272249/nicotine-promotes-human-papillomavirus-hpv-immortalized-cervical-epithelial-cells-h8-proliferation-by-activating-rps27a-mdm2-p53-pathway-in-vitro
#12
Lu Chen, Huai Wang
HPV infection is the main risk factor for cervical cancer, but it is still an insufficient event for the development of this cancer. It has demonstrated that nicotine plays an important role in cervical carcinogenesis. However, the effects and mechanisms of nicotine stimulation on precancerous lesions of cervical cancer are not clear. In this study, it showed that nicotine significantly promoted H8 cells proliferation in a concentration-dependent manner. Moreover, nicotine decreased the level of P53, resulted from a shortened P53 half-life...
October 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30272219/corrigendum-to-the-serosal-immune-system-of-the-thorax-in-toxicology
#13
Christine F Kuper, Jolanda van Bilsen, Marcel V W Wijnands
No abstract text is available yet for this article.
September 28, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30252107/the-impact-of-scaling-factor-variability-on-risk-relevant-pharmacokinetic-outcomes-in-children-a-case-study-using-bromodichloromethane-bdcm
#14
E M Kenyon, J C Lipscomb, R A Pegram, B J George, R N Hines
Biotransformation rates extrapolated from in vitro data are used increasingly in human physiologically based pharmacokinetic (PBPK) models. This practice requires use of scaling factors, including microsomal content (mg of microsomal protein/g liver, MPPGL), enzyme specific content, and liver mass as a fraction of body weight (FVL). Previous analyses indicated that scaling factor variability impacts pharmacokinetic (PK) outcomes used in adult population dose-response studies. This analysis was extended to pediatric populations because large inter-individual differences in enzyme ontogeny likely would further contribute to scaling factor variability...
September 25, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30247740/trovafloxacin-induced-liver-injury-lack-in-regulation-of-inflammation-by-inhibition-of-nucleotide-release-and-neutrophil-movement
#15
Giulio Giustarini, Nienke Vrisekoop, Laura Kruijssen, Laura Wagenaar, Selma van Staveren, Manon van Roest, Rob Bleumink, Marianne Bol-Schoenmakers, Richard Weaver, Leo Koenderman, Joost Smit, Raymond Pieters
The fluoroquinolone trovafloxacin (TVX) is associated with a high risk of drug-induced liver injury (DILI). Although part of the liver damage by TVX+TNF relies on neutrophils, we have recently demonstrated that liver recruitment of monocytes and neutrophils is delayed by TVX.Here we show that the delayed leukocyte recruitment is caused by a combination of effects which are linked to the capacity of TVX to block the hemichannel pannexin 1. TVX inhibited find-me signal release in apoptotic HepG2 hepatocytes, decelerated freshly isolated human neutrophils toward IL-8 and f-MLF, and decreased the liver expression of ICAM-1...
September 22, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30247739/regional-susceptibility-to-er-stress-and-protection-by-salubrinal-following-a-single-exposure-to-deltamethrin
#16
Muhammad M Hossain, Ganeshraj Sivaram, Jason R Richardson
Endoplasmic reticulum (ER) stress is a significant contributor to neurodegeneration and cognitive dysfunction. Recently, we reported that repeated exposure to the pyrethroid insecticide deltamethrin caused ER stress in the hippocampus of adult mice, which was accompanied by deficits in learning (Hossain et al., 2015). Here, we investigated regional susceptibility to ER stress and the ability of salubrinal, an inhibitor of ER stress, to reduce apoptosis following a single oral administration of deltamethrin (6 mg/kg)...
September 22, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30247713/differential-toxicity-of-alkylphenols-in-jeg-3-human-placental-cells-alteration-of-p450-aromatase-and-cell-lipid-composition
#17
Elisabet Pérez-Albaladejo, Silvia Lacorte, Cinta Porte
Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and foetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity and to alter the lipid composition of ten alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4-Dodecylphenol (DP), 4-heptylphenol (HP) and 4-cumylphenol (CP) showed the highest cytotoxicity (EC50: 18-65 µM). Aromatase inhibition was closely related to the hydrophobicity of APs...
September 22, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30247711/employing-dietary-comparators-to-perform-risk-assessments-for-anti-androgens-without-using-animal-data
#18
Matthew P Dent, Hequn Li, Paul L Carmichael, Francis L Martin
This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively interfered with AR signaling in vitro, using the AR CALUX® test. The IC50 values from these dose-response data together with measured or predicted human exposure levels were used to calculate exposure:activity ratios (EARs) for the dietary components and a number of other well-known anti-androgenic substances...
September 22, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30247703/identification-of-modulators-that-activate-the-constitutive-androstane-receptor-from-the-tox21-10k-compound-library
#19
Caitlin Lynch, Bryan Mackowiak, Ruili Huang, Linhao Li, Scott Heyward, Srilatha Sakamuru, Hongbing Wang, Menghang Xia
The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor involved in all phases of drug metabolism and disposition. However, recently it's been implicated in energy metabolism, tumor progression, and cancer therapy as well. It is, therefore, important to identify compounds that induce hCAR activation to predict drug-drug interactions and potential therapeutic usage. In this study, we screen the Tox21 10,000 compound collection to characterize hCAR activators. A novel structural cluster of compounds was identified, which included nitazoxanide and tenonitrozole, while known structural clusters, such as flavones and prazoles, were also detected...
September 22, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/30247698/the-developmental-neurotoxicity-of-tobacco-smoke-can-be-mimicked-by-a-combination-of-nicotine-and-benzo-a-pyrene-effects-on-cholinergic-and-serotonergic-systems
#20
Theodore A Slotkin, Samantha Skavicus, Ashley Ko, Edward D Levin, Frederic J Seidler
Tobacco smoke contains polycyclic aromatic hydrocarbons (PAHs) in addition to nicotine. We compared the developmental neurotoxicity of nicotine to that of the PAH archetype, benzo[a]pyrene (BaP), and also evaluated the effects of combined exposure to assess whether PAHs might exacerbate the adverse effects of nicotine. Pregnant rats were treated preconception through the first postnatal week, modeling nicotine concentrations in smokers and a low BaP dose devoid of systemic effects. We conducted evaluations of acetylcholine (ACh) and serotonin (5HT) systems in brain regions from adolescence through full adulthood...
September 22, 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"