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Toxicological Sciences: An Official Journal of the Society of Toxicology

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https://www.readbyqxmd.com/read/28087840/vibrio-cholerae-cholix-toxin-induced-hepg2-cell-death-is-enhanced-by-tumor-necrosis-factor-alpha-through-ros-and-intracellular-signal-regulated-kinases
#1
Kohei Ogura, Yasuhiro Terasaki, Tohru Miyoshi-Akiyama, Mika Terasaki, Joel Moss, Masatoshi Noda, Kinnosuke Yahiro
Cholix toxin (Cholix) from Vibrio cholerae is a potent virulence factor exhibiting ADP-ribosyltransferase activity on eukaryotic elongation factor 2 (eEF2) of host cells, resulting in inhibition of protein synthesis. Administration of Cholix or its homologue Pseudomonas exotoxin A (PEA) to mice causes lethal hepatocyte damage. In this study, we demonstrate cytotoxicity of Cholix on immortalized human hepatocytes in the presence of tumor necrosis factor α (TNF-α), which has been reported to play a fatal role in PEA administered to mice...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087839/understanding-the-property-activity-relationships-of-polyhedral-cuprous-oxide-nanocrystals-in-terms-of-reactive-crystallographic-facets
#2
Yanlin Feng, Yun Chang, Xiujuan Sun, Ning Liu, Yan Cheng, Yuqing Feng, Haiyuan Zhang, Xi Li
The property-activity relationship is usually established to understand the toxicity mechanism of nanomaterials. In the present study, different morphological Cu2O nanocrystals, octahedrons, truncated octahedrons, cuboctahedrons, and cubes, were synthesized to precisely tuning the {100} and {111} facet percentages in purpose of systematically investigating the toxicity role of crystallographic facets in BEAS-2B and RAW 264.7 cells. It was found that the toxicity of polyhedral Cu2O nanocrystals was highly dependent on the exposed {100} surface after short-term exposure because {100} facets could produce more reactive oxygen species (ROS) than {111} facets, however, after long-term exposure, their toxicity showed again the correlation with total surface property because toxic copper ions were largely released from the whole nanocrystal surface irrespective of {100} or {111} facet and this copper dissolution caused the collapse of surface crystals and the vanishing of ROS...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087838/does-the-assessment-of-non-disjunction-provide-a-more-sensitive-assay-for-detection-of-aneugens
#3
Joanne M Elloway, Alexandra K Davies, Julie Hayes, Ann T Doherty
The detection of aneugenic chemicals is important due to the implications of aneuploidy for human health. Aneuploidy can result from chromosome loss or non-disjunction due to chromosome mis-segregation at anaphase. Frequently, aneugens are detected using the in vitro micronucleus assay (IVM), with either centromere or kinetochore labelling. However, this method does not consider non-disjunction, the suggested predominant mechanism of spindle poison induced aneugenicity in primary human lymphocytes. Therefore, the IVM may be relatively insensitive in detecting aneuploidy...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#4
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087836/neuropathological-consequences-of-gestational-exposure-to-concentrated-ambient-fine-and-ultrafine-particles-in-the-mouse
#5
Carolyn Klocke, Joshua L Allen, Marissa Sobolewski, Margot Mayer-Pröschel, Jason L Blum, Dana Lauterstein, Judith T Zelikoff, Deborah A Cory-Slechta
Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3(rd) trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087835/study-of-tio2-p25-nanoparticles-genotoxicity-on-lung-blood-and-liver-cells-in-lung-overload-and-non-overload-conditions-after-repeated-respiratory-exposure-in-rats
#6
Charlène Relier, Marielle Dubreuil, Omar Lozano Garcia, Eugenia Cordelli, Jorge Mejia, Patrizia Eleuteri, Franck Robidel, Thomas Loret, Francesca Pacchierotti, Stéphane Lucas, Ghislaine Lacroix, Bénédicte Trouiller
Inhaled titanium dioxide (TiO2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO2 P25 NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087834/environmental-deflection-the-impact-of-toxicant-exposures-on-the-aging-epigenome
#7
Joseph Kochmanski, Luke Montrose, Jaclyn M Goodrich, Dana C Dolinoy
Epigenetic drift and age-related methylation have both been used in the literature to describe changes in DNA methylation that occurs with aging. However, ambiguity remains regarding the exact definition of both of these terms, and neither of these fields of study explicitly considers the impact of environmental factors on the aging epigenome. Recent twin studies have demonstrated longitudinal, pair-specific discordance in DNA methylation patterns, suggesting an effect of the environment on age-related methylation and/or epigenetic drift...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087833/dysregulation-of-map-kinase-signaling-pathways-including-p38mapk-sapk-jnk-and-erk1-2-in-cultured-rat-cerebellar-astrocytes-exposed-to-diphenylarsinic-acid
#8
Takayuki Negishi, Mami Matsumoto, Yayoi Kobayashi, Mikiya Kojima, Fumika Sakaguchi, Kazuaki Takahata, Tomoko Kanehira, Rina Arakaki, Yohei Aoyama, Hikari Yoshida, Rena Yamada, Nobutaka Sumiyoshi, Tomoko Tashiro, Seishiro Hirano, Kenji Yoshida, Kazunori Yukawa
Diphenylarsinic acid (DPAA) was a major compound found in the arsenic poisoning incident that occurred in Kamisu, Ibaraki, Japan in 2003. People exposed to DPAA via contaminated well water suffered from several neurological disorders, including cerebellar symptoms. We previously reported that DPAA induces cellular activation in cultured rat cerebellar astrocytes, dose-dependent promotion of cell growth (low DPAA), cell death (high DPAA), and increased phosphorylation of mitogen-activated protein (MAP) kinases (p38MAPK, SAPK/JNK, and ERK1/2)...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28082598/prenatal-exposure-to-dehp-induces-premature-reproductive-senescence-in-male-mice
#9
Radwa Barakat, Po-Ching Patrick Lin, Saniya Rattan, Emily Brehm, Igor F Canisso, Mohamed E Abosalum, Jodi A Flaws, Rex Hess, CheMyong Ko
Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate, and it is an endocrine-disrupting chemical. This study tested a hypothesis that prenatal exposure to DEHP lays the foundation for premature gonadal dysfunction and subsequent reproductive senescence in male mice. Pregnant female CD-1 mice were orally dosed with vehicle control (tocopherol-stripped corn oil) or with 20 μg/kg/day, 200 μg/kg/day, 500 mg/kg/day or 750 mg/kg/day of DEHP from gestational day 11 to birth. Overall, the prenatal DEHP exposure did not cause any overt physical health problems in male offspring, as no significant differences in their body nor gonadal weight were seen up to the age of 23 months...
January 12, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28069988/exposure-to-concentrated-ambient-pm2-5-shortens-lifespan-and-induces-inflammation-associated-signaling-and-oxidative-stress-in-drosophila
#10
Xiaoke Wang, Minjie Chen, Mianhua Zhong, Ziying Hu, Lianglin Qiu, Sanjay Rajagopalan, Nancy G Fossett, Lung-Chi Chen, Zhekang Ying
BACKGROUND: Exposure to ambient PM2.5 is associated with human premature mortality. However, it has not yet been toxicologically replicated, likely due to the lack of suitable animal models. Drosophila is frequently used in longevity research due to many incomparable merits. OBJECTIVE: The present study aims to validate Drosophila models for PM2.5 toxicity study through characterizing their biological responses to exposure to concentrated ambient PM2.5 (CAP). RESULTS: The survivorship curve demonstrated that exposure to CAP markedly reduced lifespan of Drosophila...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28069987/transgenic-zebrafish-reporter-lines-as-alternative-in-vivo-organ-toxicity-models
#11
Kar Lai Poon, Xingang Wang, Serene Gp Lee, Ashley S Ng, Wei Huang Goh, Zhonghua Zhao, Muthafar Al-Haddawi, Haishan Wang, Sinnakaruppan Mathavan, Phillip W Ingham, Claudia Mcginnis, Tom J Carney
Organ toxicity, particularly liver toxicity, remains one of the major reasons for termination of drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. A screening-amenable alternative in vivo model such as zebrafish would therefore find immediate application in the early prediction of unacceptable organ toxicity. To identify highly upregulated genes as biomarkers of toxic responses in the zebrafish model, a set of well-characterized reference drugs that cause drug induced liver injury (DILI) in the clinic were applied to zebrafish larvae and adults...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28069986/mechanisms-involved-in-porcine-early-embryo-survival-following-ethanol-exposure
#12
Florence Pagé-Larivière, Céline Campagna, Marc-André Sirard
Alcohol consumption during pregnancy is still a cause of preventable birth defects and developmental disabilities. However, little is known about the impact of ethanol on preimplantation embryos and the molecular mechanisms involved. We aimed to determine the toxicogenomic impacts and the mechanisms involved in preimplantation embryonic survival following 0.2% ethanol exposure in porcine embryos. Gene expression changes were measured with a porcine embryo specific microarray and confirmed by RT-qPCR. Compared to control, ethanol exposure led to a 43% decrease in blastocyst rate and activated pathways associated with oxidative stress and nervous system damage, such as TP53 and TGF...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28031415/evaluation-of-batch-variations-in-induced-pluripotent-stem-cell-derived-human-cardiomyocytes-from-2-major-suppliers
#13
Jianhua Huo, Archana Kamalakar, Xi Yang, Beverly Word, Norman Stockbridge, Beverly Lyn-Cook, Li Pang
Drug-induced proarrhythmia is a major safety issue in drug development. Developing sensitive in vitro assays that can predict drug-induced cardiotoxicity in humans has been a challenge of toxicology research for decades. Recently, induced pluripotent stem cell-derived human cardiomyocytes (iPSC-hCMs) have become a promising model because they largely replicate the electrophysiological behavior of human ventricular cardiomyocytes. Patient-specific iPSC-hCMs have been proposed for personalized cardiac drug selection and adverse drug response prediction; however, many procedures are involved in cardiomyocytes differentiation and purification process, which may result in large line-to-line and batch-to-batch variations...
December 28, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013220/potentiation-of-drug-induced-phospholipidosis-in-vitro-through-peglyated-graphene-oxide-as-the-nanocarrier
#14
Liecheng Yang, Xiaoyan Zhong, Qian Li, Xihui Zhang, Yangyun Wang, Kai Yang, Leshuai W Zhang
Cationic amphiphilic drugs (CADs) are small molecules that can induce phospholipidosis (PLD), causing the intracellular accumulation of phospholipid in the lamellar bodies. Nanotechnology based drug delivery systems have been used widely, while it is unknown if drug-induced PLD (DIP) can be potentiated through drug retention by indigestible nanocarriers. Due to the high drug loading capacity of graphene, we investigated if PEGylated graphene oxide (PEG-GO) loaded with CAD could potentiate DIP. Tamoxifen induced the accumulation of NBD-PE, a fluorescence labeled phospholipid in human hepatoma HepG2 cells, while PEG-GO loaded with tamoxifen (PEG-GO/tamoxifen) further potentiated PLD...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013219/the-role-of-mir-182-5p-in-hepatocarcinogenesis-of-trichloroethylene-in-mice
#15
Yan Jiang, Jiahong Chen, Cong Yue, Hang Zhang, Jian Tong, Jianxiang Li, Tao Chen
Trichloroethylene (TCE), commonly used as an industrial solvent, is ubiquitous in our living environment. TCE exposure can induce hepatocellular carcinoma (HCC) in mice, but the underlying mechanisms remain elusive. To understand the role of miRNA in the hepatocarcinogenesis of TCE, we examined the miRNA expression profiles by microarray in the liver of B6C3F1 male mice exposed to TCE at 0 or 1000 mg/kg b.w.. Nine differentially expressed miRNAs were identified, out of which miR-182-5p exhibited the highest increase in expression...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013218/genetic-targets-of-acute-toluene-inhalation-in-drosophila-melanogaster
#16
Philip J Bushnell, William Ward, Tatiana V Morozova, Wendy M Oshiro, Mimi T Lin, Richard S Judson, Susan D Hester, John M McKee, Mark Higuchi
Interpretation and use of data from high-throughput assays for chemical toxicity require links between effects at molecular targets and adverse outcomes in whole animals. The well-characterized genome of Drosophila melanogaster provides a potential model system by which phenotypic responses to chemicals can be mapped to genes associated with those responses, which may in turn suggest adverse outcome pathways associated with those genes. To determine the utility of this approach, we used the Drosophila Genetics Reference Panel (DGRP), a collection of ~200 homozygous lines of fruit flies whose genomes have been sequenced...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013217/strain-and-sex-differences-in-the-vestibular-and-systemic-toxicity-of-3-3-iminodipropionitrile-in-mice
#17
Pere Boadas-Vaello, Lara Sedó-Cabezón, Enrique Verdú, Jordi Llorens
The nitrile 3,3'-iminodipropionitrile (IDPN) causes a loss of hair cells in the vestibular epithelium of the inner ear in several species of both mammals and non-mammals. It is of interest as a model compound in ototoxicity and vestibular regeneration research, but its effects on the mouse, including the potential relevance of strain and sex differences for susceptibility, have not yet been thoroughly characterized. In this study, we compared the vestibular toxicity of IDPN in dose-response studies (0, 8, 12, 16 and 24 mmol/kg IDPN p...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013216/diesel-exhaust-particles-contribute-to-endothelia-apoptosis-via-autophagy-pathway
#18
Jhih-Syuan Wang, Chia-Yi Tseng, Ming-Wei Chao
Epidemiological studies suggest that an increase of PM2.5 diesel exhaust particles (DEP) in ambient air corresponds to increased myocardial infarctions and atherosclerosis. When exposed to DEP, endothelial cells exhibit increases in oxidative stress and apoptosis, but the role of autophagy in this DEP-induced cell death remains unclear. Here, we suggest that acute DEP exposure produces intracellular ROS leading to induction of DEP internalization, endothelial dysfunction, and pro-inflammation in an in vitro HUVEC model...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013215/organic-anion-transporting-polypeptides-contribute-to-the-disposition-of-perfluoroalkyl-acids-in-humans-and-rats
#19
Wen Zhao, Jeremiah D Zitzow, Yi Weaver, David J Ehresman, Shu-Ching Chang, John L Butenhoff, Bruno Hagenbuch
Perfluoroalkyl sulfonates (PFSAs) such as perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) have very long serum elimination half-lives in humans, and preferentially distribute to serum and liver. The enterohepatic circulation of PFHxS and PFOS likely contributes to their extended elimination half-lives. We previously demonstrated that perfluorobutane sulfonate (PFBS), PFHxS, and PFOS are transported into hepatocytes both in a sodium-dependent and a sodium-independent manner. We identified Na(+)/taurocholate cotransporting polypeptide (NTCP) as the responsible sodium-dependent transporter...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013214/effects-of-an-environmentally-relevant-phthalate-mixture-on-cultured-mouse-antral-follicles
#20
Changqing Zhou, Jodi A Flaws
Phthalates are used in building materials, medical devices, and personal care products. Most studies on phthalates have focused on single phthalates, but it is important to study mixtures of phthalates because humans are exposed to such mixtures daily. We tested the hypothesis that phthalate mixture exposure decreases antral follicle growth, compromises steroidogenic capacity, and induces atresia. Antral follicles from adult CD-1 mice were cultured with vehicle control or phthalate mixture (1-500 μg/ml) for 96 hours...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
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