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Toxicology Letters

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https://www.readbyqxmd.com/read/29787794/early-growth-response-gene-1-is-essential-for-urban-particulate-matter-induced-inflammation-and-mucus-hyperproduction-in-airway-epithelium
#1
Feng Xu, Jiaofei Cao, Man Luo, Luanqing Che, Wen Li, Songmin Ying, Zhihua Chen, Huahao Shen
Particulate matter (PM) has been implicated as a risk factor for human airway disorders. However, the biological mechanisms underlying the correlation between PM exposure and adverse airway effects have not yet been fully clarified. The objective of this study was to explore the possible role of early growth response gene 1 (Egr-1) in PM-induced toxic effects in pulmonary inflammation and mucus hyperproduction in vitro and in vivo. Particulate matter exposure induced a rapid Egr-1 expression in human bronchial epithelial (HBE) cells and in mouse lungs...
May 19, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29778912/alcohol-inhibits-the-proliferation-of-neuro2a-cells-via-promoting-the-asymmetric-cell-division-through-down-regulation-of-the-expression-of-centrosome-protein-j
#2
Tao Xu, Shan-Yu Zhang, Xiao-Mei Xu, Shuai Zhao, Kai-Heng Zhu, Wei-Wei Zhang, Ling-Li Zhao
Alcohol can decrease cell proliferation in neural cells. The proliferation of neural cells can be inhibited by the asymmetric division of neural progenitor cells. However, whether alcohol inhibits cell proliferation through inducing cell asymmetric division is not yet clear. Here, we reported that the percentage of asymmetric division was increased in alcohol-treated Neuro2a cells owing to the impaired-spindle orientation. Meanwhile, the expression of Centrosome protein-J (CPAP) which plays an important role in spindle orientation was reduced in Neuro2a cells...
May 17, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29778911/exposure-to-diethylhexyl-phthalate-dehp-and-monoethylhexyl-phthalate-mehp-promotes-the-loss-of-alveolar-epithelial-phenotype-of-a549-cells
#3
L Rafael-Vázquez, García-Trejo Semiramis, O G Aztatzi-Aguilar, B Bazán-Perkins, B Quintanilla-Vega
Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is metabolized to mono(2-ethylhexyl) phthalate (MEHP). Inhalation is an important exposure route for both phthalates, and their effects on lungs include inflammation, alteration of postnatal maturation (alveolarization), enlarged airspaces and cell differentiation changes, suggesting that alveolar epithelial cells-2 (AEC) are targets of phthalates. This study evaluated the cell progression, epithelial and mesenchymal markers, including surfactant secretion in A549 cells (AEC) that were exposed to DEHP (1-100 µM) or MEHP (1-50 µM) for 24-72 h...
May 17, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29777833/endocrine-disrupting-activities-and-immunomodulatory-effects-in-lymphoblastoid-cell-lines-of-diclofenac-4-hydroxydiclofenac-and-paracetamol
#4
Ivana Klopčič, Tijana Markovič, Irena Mlinarič-Raščan, Marija Sollner Dolenc
A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR)...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29777832/novel-cysteine-and-albumin-adduct-biomarkers-to-prove-human-poisoning-with-the-pesticide-oxydemeton-s-methyl
#5
Harald John, Markus Siegert, Florian Eyer, Franz Worek, Horst Thiermann, Andreas Kranawetvogl
We herein report on the forensic analysis of plasma samples to prove human poisoning with oxydemeton-S-methyl (ODM), S-(2-(ethylsulfinyl)ethyl)-O,O-dimethyl phosphorothioate. This organophosphorus pesticide is the active ingredient of Metasystox® , that was swallowed by a 77-year-old woman to commit suicide. ODM belongs to the class of dimethyl phosphoryl (DMP) pesticides, contains a 2-(ethylsulfinyl)ethanethiol (ESOET) leaving group and undergoes adduct formation with endogenous molecules as elaborated herein with human serum exposed to pesticides in vitro...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29777831/microcystis-bloom-containing-microcystin-lr-induces-type-2-diabetes-mellitus
#6
Qiong Zhang, Wendi Qin, Liuyan Yang, Jing An, Xuxiang Zhang, Hao Hong, Lizhi Xu, Yaping Wang
Epidemiological data from Lake Taihu showed significantly higher incidences of type 2 diabetes mellitus (T2DM) than in other areas of China. This may be related to the occurrence of a Microcystis bloom in Lake Taihu in the summer and autumn every year. The objective of this study is to investigate whether the contaminated water from the Microcystis bloom and the derivative pollutant microcystin-LR (MC-LR) can explain the higher incidences of T2DM. Healthy male mice were fed with water from different regions of Lake Taihu, and were either acutely or chronically exposed to MC-LR through oral administration or intraperitoneal injection...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29775723/a-scale-out-approach-towards-neural-induction-of-human-induced-pluripotent-stem-cells-for-neurodevelopmental-toxicity-studies
#7
Cláudia C Miranda, Tiago G Fernandes, Sandra N Pinto, Manuel Prieto, M Margarida Diogo, Joaquim M S Cabral
Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29775722/inflammatory-and-oxidative-mechanisms-potentiate-bifenthrin-induced-neurological-alterations-and-anxiety-like-behavior-in-adult-rats
#8
Brahim Gargouri, Harsharan S Bhatia, Michèle Bouchard, Bernd L Fiebich, Hamadi Fetoui
Bifenthrin (BF) is a synthetic pyrethroid pesticide widely used in several countries to manage insect pests on diverse agricultural crops. Growing evidence indicates that BF exposure is associated with an increased risk of developing neurodegenerative disorders. However, the mechanisms by which BF induces neurological and anxiety alterations in the frontal cortex and striatum are not well known. The present in vivo study was carried out to determine whether reactive oxygen species (ROS)-mediated oxidative stress (OS) and neuroinflammation are involved in such alterations...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29775721/critical-evaluation-of-2-ethylhexyl-acrylate-dermal-carcinogenicity-studies-using-contemporary-criteria
#9
REVIEW
Sandra Murphy, Robert Ellis-Hutchings, Lavorgie Finch, Stefanie Welz, Karin Wiench
Skin tumors have been observed in C3H/HeJ mice following treatment with high and strongly irritating concentrations of 2-ethylhexyl acrylate (2-EHA). Dermal carcinogenicity studies performed with 2-EHA are reviewed, contrasting the results in two mouse strains (C3H/HeJ and NMRI) under different dosing regimens. Application of contemporary evaluation criteria to the existing dermal carcinogenicity dataset demonstrates that 2-EHA induces skin tumors only at concentrations exceeding an maximum tolerated dose (MTD) and in the immune-dysregulated C3H/HeJ mouse model...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29772265/administration-of-low-dose-triclosan-to-pregnant-ewes-results-in-placental-uptake-and-reduced-estradiol-sulfotransferase-activity-in-fetal-liver-and-placenta
#10
Erin N Jackson, Laura Rowland-Faux, Margaret O James, Charles E Wood
Sulfonation is a major pathway of estrogen biotransformation with a role in regulating estrogen homeostasis in humans and sheep. Previous in vitro studies found that triclosan is an especially potent competitive inhibitor of ovine placental estrogen sulfotransferase, with Kic of <0.1 nM. As the placenta is the main organ responsible for estrogen synthesis in pregnancy in both women and sheep, and the liver is another site of estrogen biotransformation, this study examined the effects of triclosan exposure of pregnant ewes on placental and hepatic sulfotransferase activity...
May 14, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29763686/mice-deficient-in-aldo-keto-reductase-1a-akr1a-are-resistant-to-thioacetamide-induced-liver-injury
#11
Takujiro Homma, Takaya Shirato, Ryusuke Akihara, Sho Kobayashi, Jaeyong Lee, Ken-Ichi Yamada, Satoshi Miyata, Motoko Takahashi, Junichi Fujii
Aldehyde reductase (Akr1a) has been reported to be involved in detoxification of reactive aldehydes as well as in the synthesis of bioactive compounds such as ascorbic acid (AsA). Because Akr1a is expressed at high levels in the liver and is involved in xenobiotic metabolism, our objective was to investigate the hepato-protective role of Akr1a in a thioacetamide (TAA)-induced hepatotoxicity model using Akr1a-deficient (Akr1a-/- ) mice. Wild-type (WT) and Akr1a-/- mice were injected intraperitoneally with TAA and the extent of liver injury in the acute phase was assessed...
May 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29763685/autophagy-plays-a-pro-survival-role-against-methamphetamine-induced-apoptosis-in-h9c2-cells
#12
Chao Zhao, Yong Mei, Xufeng Chen, Lei Jiang, Yunfei Jiang, Xu Song, Hang Xiao, Jun Wang, Jingsong Zhang
Methamphetamine (METH) is a commonly abused psychostimulant that can induce severe neurotoxicity. Cardiovascular injury caused by METH has recently gained increasing attention; however, the underlying mechanisms remain unclear. As autophagy has been shown to be associated with cell injury, the association between autophagy and METH-mediated cell apoptosis was investigated in the present study. METH treatment significantly increased the expression of two key autophagy proteins, i.e., Beclin-1 and LC3-II, in the cardiomyocyte cell line H9C2...
May 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758360/single-ingestion-of-di-2-propylheptyl-phthalate-dphp-by-male-volunteers-dphp-in-blood-and-its-metabolites-in-blood-and-urine
#13
D Klein, W Kessler, C Pütz, B Semder, W Kirchinger, A Langsch, W Gries, R Otter, A K E Gallien, X Wurzenberger, J G Filser
Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP)...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758359/probing-flecainide-block-of-i-na-using-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes-adapted-to-automated-patch-clamping-and-2d-monolayers
#14
Lin Geng, Chi-Wing Kong, Andy O T Won, Angie Man-Yee Shum, Maggie Z Y Chow, Hui Che, Chenzi Zhang, Ka-Long Yau, Camie W Chan, Wendy Keung, Ronald A Li
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are emerging tools for applications such as drug discovery and screening for pro-arrhythmogenicity and cardiotoxicity as leading causes for drug attrition. Understanding the electrophysiology (EP) of hPSC-CMs is essential but conventional manual patch-clamping is highly laborious and low-throughput. Here we adapted hPSC-CMs derived from two human embryonic stem cell (hESC) lines, HES2 and H7, for a 16-channel automated planar-recording approach for single-cell EP characterization...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758358/lipidomic-signature-of-serum-from-the-rats-exposed-to-alcohol-for-one-year
#15
Hongchun Li, Wei Xu, Linhong Jiang, Hui Gu, Menglu Li, Jiamei Zhang, Wei Guo, Pengchi Deng, Hailei Long, Qian Bu, Jingwei Tian, Yinglan Zhao, Xiaobo Cen
Alcohol abuse and its related diseases are the major risk factors for human health. Although the mechanism of alcohol-related disorders has been widely investigated, serum metabolites associated with long-term alcohol intake have not been well explored. In this study, we aimed to investigate the profiles of serum metabolites and lipid species of rats chronically exposed to alcohol, which may be involved in the pathogenesis of alcohol-associated disease. An 1 H NMR-based metabolomics and Q-TOF/MS-based lipidomics approach were applied to investigate the profile of serum metabolites and lipid species of rats administrated daily with alcohol (12% vol/vol, 10 ml/kg per day, i...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29753845/gestational-di-2-ethylhexyl-phthalate-exposure-causes-fetal-intrauterine-growth-restriction-through-disturbing-placental-thyroid-hormone-receptor-signaling
#16
Zhen Yu, Yan Han, Ru Shen, Kun Huang, Yuan-Yuan Xu, Qu-Nan Wang, Shan-Shan Zhou, De-Xiang Xu, Fang-Biao Tao
Previous study reported that gestational Di-(2-ethylhexyl) phthalate (DEHP) exposure caused fetal intrauterine growth restriction (IUGR). We aimed to investigate the role of placental thyroid hormone receptor (THR) signaling in DEHP-induced IUGR. Dams were treated with DEHP (50 or 200 mg/kg) by gavage daily throughout pregnancy. As expected, gestational DEHP exposure dose-dependently caused fetal IUGR. The mRNA levels of placental Thrα1 and Thrβ1 were reduced and nuclear translocation of placental THRα1 and THRβ1 were suppressed in DEHP-exposed mice even though thyroid hormones in maternal and fetal sera were unaffected...
May 10, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29753068/perfluorooctanoic-acid-stimulates-ovarian-cancer-cell-migration-invasion-via-erk-nf-%C3%AE%C2%BAb-mmp-2-9-pathway
#17
Xiaozhao Li, Chunyu Bao, Zhinan Ma, Boqun Xu, Xiaoqiu Liu, Xiaoyan Ying, Xuesen Zhang
As widely used in consumer products, perfluorooctanoic acid (PFOA) has become a common environmental pollutant, which has been detected in human serum and associated with cancers. Our previous study showed that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Here, we showed that PFOA (≥100 nM) treatment also stimulated A2780 ovarian cancer cell invasion and migration, which correlated with increased matrix metalloproteinases MMP-2/-9 expression, important proteases associated with tumor invasion and migration...
May 9, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29753067/drug-interaction-study-of-flavonoids-toward-cyp3a4-and-their-quantitative-structure-activity-relationship-qsar-analysis-for-predicting-potential-effects
#18
Yannan Li, Jing Ning, Yan Wang, Chao Wang, Chengpeng Sun, Xiaokui Huo, Zhenlong Yu, Lei Feng, Baojing Zhang, Xiangge Tian, Xiaochi Ma
The high risk of herb-drug interactions (HDIs) mediated by the herbal medicines and dietary supplements which containing abundant flavonoids had become more and more frequent in our daily life. In our study, the inhibition activities of 44 different structures of flavonoids toward human CYPs were systemically evaluated for the first time. According to our results, a remarkable structure-dependent inhibition behavior toward CYP3A4 was observed in vitro. Some flavonoids such as licoflavone (12) and irilone (30) exhibited the selective inhibition toward CYP3 A4 rather than other major human CYPs...
May 9, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29751043/tauroursodeoxycholic-acid-attenuates-gentamicin-induced-cochlear-hair-cell-death-in-vitro
#19
Zhanwei Jia, Qiang He, Chunguang Shan, Fengyi Li
Gentamycin is one of the most clinically used aminoglycoside antibiotics which induce intrinsic apoptosis of hair cells. Tauroursodeoxycholic acid (TUDCA) is known as safe cell-protective agent in disorders associated with apoptosis. We aimed to investigate the protective effects of TUDCA against gentamicin-induced ototoxicity. House Ear Institute-Organ of Corti 1(HEI-OC1) cells and explanted cochlear tissue were treated with gentamicin and TUDCA, followed by serial analyses including cell viability assay, hair cell staining, qPCR, ELISA and western blotting to determine the cell damage by the parameters relevant to cell apoptosis and endoplasmic reticulum stress...
May 8, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29746905/chronic-lead-exposure-induces-cochlear-oxidative-stress-and-potentiates-noise-induced-hearing-loss
#20
Samson Jamesdaniel, Rita Rosati, Judy Westrick, Douglas M Ruden
Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise...
May 7, 2018: Toxicology Letters
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