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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/28549829/impact-of-chlorpyrifos-on-human-villous-trophoblasts-and-chorionic-villi
#1
M E Ridano, A C Racca, J B Flores-Martin, R Fretes, C L Bandeira, L Reyna, E Bevilacqua, S Genti-Raimondi, G M Panzetta-Dutari
Placental barrier regulates maternal-fetal interchange protecting the baby from damage caused by substances found in the uterine environment or circulating in the vascular system. Organophosphate (OP) pesticides are a paramount group of environmental pollutants used in intensive agriculture for protection against diseases and pests. While many studies have reported an increased risk of pregnancy alterations in pregnant women exposed to OPs, few have analyzed the effects caused by these pesticides in the placenta...
May 23, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28549828/deficiency-of-long-isoforms-of-nfe2l1-sensitizes-min6-pancreatic-%C3%AE-cells-to-arsenite-induced-cytotoxicity
#2
Qi Cui, Jingqi Fu, Yuxin Hu, Yongfang Li, Bei Yang, Lu Li, Jing Sun, Chengjie Chen, Guifan Sun, Yuanyuan Xu, Qiang Zhang, Jingbo Pi
Increasing evidence indicates that chronic inorganic arsenic exposure is associated with type 2 diabetes (T2D), a disease of growing prevalence. Pancreatic β-cells were targeted and damaged by oxidative stress induced by arsenite. We previously showed that nuclear factor erythroid 2 like 2 (Nfe2l2)-deficient pancreatic β-cells were vulnerable to cell damage induced by oxidative stressors including arsenite, due to a muted antioxidant response. Like nuclear factor erythroid 2 like 2 (NFE2L2), NFE2L1 also belongs to the cap 'n' collar (CNC) basic-region leucine zipper (bZIP) transcription factor family, and regulates antioxidant response element (ARE) related genes...
May 23, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28546047/an-impedance-based-approach-using-human-ipsc-derived-cardiomyocytes-significantly-improves-in-vitro-prediction-of-in-vivo-cardiotox-liabilities
#3
Bryan Koci, Gregory Luerman, Anika Duenbostell, Ralf Kettenhofen, Heribert Bohlen, Luke Coyle, Brian Knight, Warren Ku, Walter Volberg, Joseph R Woska, Martha P Brown
Current in vitro approaches to cardiac safety testing typically focus on mechanistic ion channel testing to predict in vivo proarrhythmic potential. Outside of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, structural and functional cardiotoxicity related to chronic dosing effects are of great concern as these effects can impact compound attrition. Development and implementation of an in vitro cardiotoxicity screening platform that effectively identifies these liabilities early in the discovery process should reduce costly attrition and decrease preclinical development time...
May 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28536007/zuotai-and-hgs-differ-from-hgcl2-and-methyl-mercury-in-hg-accumulation-and-toxicity-in-weanling-and-aged-rats
#4
Bin-Bin Zhang, Wen-Kai Li, Wei-Yu Hou, Ya Luo, Jing-Zhen Shi, Cen Li, Li-Xin Wei, Jie Liu
Mercury sulfides are used in Ayurvedic medicines, Tibetan medicines, and Chinese medicines for thousands of years and are still used today. Cinnabar (α-HgS) and metacinnabar (β-HgS) are different from mercury chloride (HgCl2) and methylmercury (MeHg) in their disposition and toxicity. Whether such scenario applies to weanling and aged animals is not known. To address this question, weanling (21d) and aged (450d) rats were orally given Zuotai (54% β-HgS, 30mg/kg), HgS (α-HgS, 30mg/kg), HgCl2 (34.6mg/kg), or MeHg (MeHgCl, 3...
May 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28532672/molecular-insights-into-the-differences-in-anti-inflammatory-activities-of-green-tea-catechins-on-il-1%C3%AE-signaling-in-rheumatoid-arthritis-synovial-fibroblasts
#5
Sabrina Fechtner, Anil Singh, Mukesh Chourasia, Salahuddin Ahmed
In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity...
May 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28532671/ochratoxin-a-transport-by-the-human-breast-cancer-resistance-protein-bcrp-multidrug-resistance-protein-2-mrp2-and-organic-anion-transporting-polypeptides-1a2-1b1-and-2b1
#6
Xiaozhe Qi, Els Wagenaar, Wentao Xu, Kunlun Huang, Alfred H Schinkel
Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pH7...
May 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28529118/early-life-allergen-and-air-pollutant-exposures-alter-longitudinal-blood-immune-profiles-in-infant-rhesus-monkeys
#7
Candace M Crowley, Justin H Fontaine, Joan E Gerriets, Edward S Schelegle, Dallas M Hyde, Lisa A Miller
Early life is a critical period for the progressive establishment of immunity in response to environmental stimuli; the impact of airborne challenges on this process is not well defined. In a longitudinal fashion, we determined the effect of episodic house dust mite (HDM) aerosol and ozone inhalation, both separately and combined, on peripheral blood immune cell phenotypes and cytokine expression from 4 to 25weeks of age in an infant rhesus monkey model of childhood development. Immune profiles in peripheral blood were compared with lung lavage at 25weeks of age...
May 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527916/cadmium-stimulates-metastasis-associated-phenotype-in-triple-negative-breast-cancer-cells-through-integrin-and-%C3%AE-catenin-signaling
#8
Zhengxi Wei, Zahir A Shaikh
Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer development. While the mechanisms of Cd-induced breast cancer initiation and promotion have been studied, the molecular processes involved in breast cancer progression remain to be investigated. The purpose of the present study was to evaluate the influence of Cd on metastasis-associated phenotypes, such as cell adhesion, migration, and invasion in triple-negative breast cancer cells. Treatment of MDA-MB-231 cells with 1μM Cd increased cell spreading and cell migration...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527915/methylparaben-and-butylparaben-alter-multipotent-mesenchymal-stem-cell-fates-towards-adipocyte-lineage
#9
Pan Hu, Haley Overby, Emily Heal, Shu Wang, Jiangang Chen, Chwan-Li Shen, Ling Zhao
Paraben esters and their salts are widely used as preservatives in cosmetics, personal care products, pharmaceuticals, and foods. We previously reported that parabens promoted adipocyte differentiation in vitro and increased adiposity but suppressed serum marker of bone formation in vivo. Here, we investigated the effects of parabens (methylparaben and butylparaben) on modulating cell fate of multipotent stem cell line C3H10T1/2. Both parabens modulated adipogenic, osteogenic, and chondrogenic differentiation of C3H10T1/2 cells in vitro...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527914/impact-of-hepatic-p450-mediated-biotransformation-on-the-disposition-and-respiratory-tract-toxicity-of-inhaled-naphthalene
#10
Nataliia Kovalchuk, Jacklyn Kelty, Lei Li, Matthew Hartog, Qing-Yu Zhang, Patricia Edwards, Laura Van Winkle, Xinxin Ding
We determined whether a decrease in hepatic microsomal cytochrome P450 activity would impact lung toxicity induced by inhalation exposure to naphthalene (NA), a ubiquitous environmental pollutant. The liver-Cpr-null (LCN) mouse showed decreases in microsomal metabolism of NA in liver, but not lung, compared to wild-type (WT) mouse. Plasma levels of NA and NA-glutathione conjugates (NA-GSH) were both higher in LCN than in WT mice after a 4-h nose-only NA inhalation exposure at 10ppm. Levels of NA were also higher in lung and liver of LCN, compared to WT, mice, following exposure to NA at 5 or 10ppm...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527913/von-willebrand-factor-deficiency-reduces-liver-fibrosis-in-mice
#11
Nikita Joshi, Anna K Kopec, Jessica L Ray, Holly Cline-Fedewa, Dafna J Groeneveld, Ton Lisman, James P Luyendyk
Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28526636/rebamipide-ameliorates-radiation-induced-intestinal-injury-in-a-mouse-model
#12
Sehwan Shim, Hyo-Sun Jang, Hyun-Wook Myung, Jae Kyung Myung, Jin-Kyu Kang, Min-Jung Kim, Seung Bum Lee, Won-Suk Jang, Sun-Joo Lee, Young-Woo Jin, Seung-Sook Lee, Sunhoo Park
Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased...
May 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28526635/arsenic-exposures-alter-clinical-indicators-of-anemia-in-a-male-population-of-smokers-and-non-smokers-in-bangladesh
#13
Faruque Parvez, Sebastian Medina, Regina Santella, Tariqul Islam, Fredine T Lauer, Nur Alam, Mahbubul Eunus, Mizanour Rahman, Pam Factor-Litvak, Habib Ahsan, Joseph Graziano, Ke Jian Liu, Scott W Burchiel
Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh...
May 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28522354/corrigendum-to-differential-effects-of-the-persistent-ddt-metabolite-methylsulfonyl-dde-in-nonstimulated-and-lh-stimulated-neonatal-porcine-leydig-cells-toxicology-and-applied-pharmacology-267-2013-247-255
#14
Cesilie Granum Castellanos, Irene Beate Sørvik, Marte Bruu Tanum, Steven Verhaegen, Ingvar Brandt, Erik Ropstad
No abstract text is available yet for this article.
May 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28506836/a-comprehensive-review-of-metal-induced-cellular-transformation-studies
#15
Qiao Yi Chen, Max Costa
In vitro transformation assays not only serve practical purposes in screening for potential carcinogenic substances in food, drug, and cosmetic industries, but more importantly, they provide a means of understanding the critical biological processes behind in vivo cancer development. In resemblance to cancer cells in vivo, successfully transformed cells display loss of contact inhibition, gain of anchorage independent growth, resistant to proper cell cycle regulation such as apoptosis, faster proliferation rate, potential for cellular invasion, and ability to form tumors in experimental animals...
May 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28506835/impact-of-common-clandestine-structural-modifications-on-synthetic-cathinone-bath-salt-pharmacokinetics
#16
Gregory G Grecco, David F Kisor, Joseph S Magura, Jon E Sprague
Since 2009, the synthetic cathinones ("bath salts") have risen in popularity as drugs of abuse. However, there are a paucity of studies that have determined the impact of functional group modifications in the synthetic cathinone chemical structures on plasma and central nervous system (CNS) pharmacokinetics. In the present study, we investigated the in vivo plasma and CNS pharmacokinetics of three synthetic cathinones whose structures differ by lengthening of the α-alkyl chain: methylone (-CH3), butylone (-CH2CH3), and pentylone (-CH2CH2CH3)...
May 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28506834/safety-evaluation-of-dermal-exposure-to-phthalates-metabolism-dependent-percutaneous-absorption
#17
Masahiro Sugino, Tomomi Hatanaka, Hiroaki Todo, Yuko Mashimo, Takamasa Suzuki, Miho Kobayashi, Osamu Hosoya, Hideto Jinno, Kazuhiko Juni, Kenji Sugibayashi
Phthalates, known as reproductive toxicants and endocrine disruptors, are widely used as plasticizers in polyvinyl chloride products. The present study was conducted for risk identification of dermal exposure to phthalates. When dibutyl phthalate was applied to the skin of hairless rats and humans, only monobutyl phthalate appeared through the skin, and the permeability of the skin was higher than that after the application of the monoester directly. The inhibition of skin esterases made the skin impermeable to the metabolite following dermal exposure to dibutyl ester, whereas removal of the stratum corneum from the skin did not change the skin permeation behavior...
May 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28502886/hmga2-a-driver-of-inflammation-is-associated-with-hypermethylation-in-acute-liver-injury
#18
Huimin Huang, Haidi Li, Xin Chen, Yang Yang, Xiaofeng Li, Wanxia Li, Cheng Huang, Xiaoming Meng, Lei Zhang, Jun Li
Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs as a driver at critical stage of hepatocellular carcinoma, herein, we investigated the role of HMGA2 in macrophage activation during ALI. Our study found that the expression of HMGA2 decreased dramatically both in KCs isolated from the liver in mice with ALI and in LPS-induced RAW264...
May 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28501332/inhibition-of-nicotinamide-phosphoribosyltransferase-and-depletion-of-nicotinamide-adenine-dinucleotide-contribute-to-arsenic-trioxide-suppression-of-oral-squamous-cell-carcinoma
#19
Xin Yue Wang, Jin Zhi Wang, Lu Gao, Fu Yin Zhang, Qi Wang, Ke Jian Liu, Bin Xiang
Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase (NAMPT) expression is associated with the development and prognosis of many cancers, but it remains unknown regarding its role in oral squamous cell carcinoma (OSCC). In the present study, the results from tissue microarray showed that NAMPT was overexpressed in OSCC patients and its expression level was directly correlated with differential grades of cancer. Interestingly, treatment of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels of NAMPT protein and increased cellular death in an ATO dose- and time-dependent manner...
May 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28501331/the-expression-of-keratin-6-is-regulated-by-the-activation-of-the-erk1-2-pathway-in-arsenite-transformed-human-urothelial-cells
#20
Andrea Slusser-Nore, Scott H Garrett, Xu Dong Zhou, Donald A Sens, Mary Ann Sens, Seema Somji
Urothelial cancers have an environmental etiological component, and previous studies from our laboratory have shown that arsenite (As(+3)) can cause the malignant transformation of the immortalized urothelial cells (UROtsa), leading to the expression of keratin 6 (KRT6). The expression of KRT6 in the parent UROtsa cells can be induced by the addition of epidermal growth factor (EGF). Tumors formed by these transformed cells have focal areas of squamous differentiation that express KRT6. The goal of this study was to investigate the mechanism involved in the upregulation of KRT6 in urothelial cancers and to validate that the As(+3)-transformed UROtsa cells are a model of urothelial cancer...
May 10, 2017: Toxicology and Applied Pharmacology
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