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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/28315692/role-of-epithelial-mesenchymal-transition-emt-and-fibroblast-function-in-cerium-oxide-nanoparticles-induced-lung-fibrosis
#1
Jane Ma, Bridget Bishoff, R R Mercer, Mark Barger, Diane Schwegler-Berry, Vincent Castranova
The emission of cerium oxide nanoparticles (CeO2) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO2-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO2 (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28315356/the-effect-of-angiotensin-receptor-neprilysin-inhibitor-sacubitril-valsartan-on-central-nervous-system-amyloid-%C3%AE-concentrations-and-clearance-in-the-cynomolgus-monkey
#2
Heidi A Schoenfeld, Tim West, Philip B Verghese, Mary Holubasch, Neeta Shenoy, David Kagan, Chiara Buono, Wei Zhou, Marc DeCristofaro, Julie Douville, Geoffrey G Goodrich, Keith Mansfield, Chandra Saravanan, Frederic Cumin, Randy L Webb, Randall J Bateman
Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28300557/high-fat-diet-aggravates-2-2-4-4-tetrabromodiphenyl-ether-inhibited-testosterone-production-via-dax-1-in-leydig-cells-in-rats
#3
Zhan Zhang, Yongquan Yu, Hengsen Xu, Chao Wang, Minghui Ji, Jun Gu, Lu Yang, Jiansheng Zhu, Huibin Dong, Shou-Lin Wang
Growing evidence has revealed that a high-fat diet (HFD) could lead to disorders of glycolipid metabolism and insulin-resistant states, and HFDs have been associated with the inhibition of testicular steroidogenesis. Our previous study demonstrated that 2,2',4,4'-tetrabromodiphenyl ether (BDE47) could increase the risk of diabetes in humans and reduce testosterone production in rats. However, whether the HFD affects BDE47-inhibited testosterone production by elevating insulin levels and inducing related pathways remains unknown...
March 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28286118/maternal-exposure-to-di-2-ethylhexyl-phthalate-dehp-promotes-the-transgenerational-inheritance-of-adult-onset-reproductive-dysfunctions-through-the-female-germline-in-mice
#4
Paola Pocar, Nadia Fiandanese, Anna Berrini, Camillo Secchi, Vitaliano Borromeo
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0...
March 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28286117/carvedilol-prevents-functional-deficits-in-peripheral-nerve-mitochondria-of-rats-with-oxaliplatin-evoked-painful-peripheral-neuropathy
#5
Aparna Areti, Prashanth Komirishetty, Ashutosh Kumar
Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a)...
March 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28286116/biatriosporin-d-displays-anti-virulence-activity-through-decreasing-the-intracellular-camp-levels
#6
Ming Zhang, Wenqiang Chang, Hongzhuo Shi, Yanhui Zhou, Sha Zheng, Ying Li, Lin Li, Hongxiang Lou
Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans...
March 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28284858/inhibition-of-potassium-currents-is-involved-in-antiarrhythmic-effect-of-moderate-ethanol-on-atrial-fibrillation
#7
Baode Yang, Chenxing Li, Junyi Sun, Xinghui Wang, Xinling Liu, Chun Yang, Lina Chen, Jun Zhou, Hao Hu
Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF...
March 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28284859/molecular-mechanisms-of-3-3-4-4-5-pentachlorobiphenyl-induced-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma-cells
#8
Li Song, Linlin Guo, Zhuoyu Li
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration...
March 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28284857/trpa1-acrolein-meets-its-target
#9
Satyanarayana Achanta, Sven-Eric Jordt
No abstract text is available yet for this article.
March 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28283350/ultrafine-carbon-particles-promote-rotenone-induced-dopamine-neuronal-loss-through-activating-microglial-nadph-oxidase
#10
Yinxi Wang, Dan Liu, Huifeng Zhang, Yixin Wang, Ling Wei, Yutong Liu, Jieying Liao, Hui-Ming Gao, Hui Zhou
BACKGROUND: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. METHODS: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures...
March 7, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28263824/suppressive-immunoregulatory-effects-of-three-antidepressants-via-inhibition-of-the-nuclear-factor-%C3%AE%C2%BAb-activation-assessed-using-primary-macrophages-of-carp-cyprinus-carpio
#11
Wenhui Qiu, Minghong Wu, Shuai Liu, Bei Chen, Chenyuan Pan, Ming Yang, Ke-Jian Wang
Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokine gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6h-exposure to three individual antidepressants and a combination thereof...
March 3, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28263823/embryotoxic-and-pharmacologic-potency-ranking-of-six-azoles-in-the-rat-whole-embryo-culture-by-morphological-and-transcriptomic-analysis
#12
Myrto Dimopoulou, Aart Verhoef, Jeroen L A Pennings, Bennard van Ravenzwaay, Ivonne M C M Rietjens, Aldert H Piersma
Differential gene expression analysis in the rat whole embryo culture (WEC) assay provides mechanistic insight into the embryotoxicity of test compounds. In our study, we hypothesized that comparative analysis of the transcriptomes of rat embryos exposed to six azoles (flusilazole, triadimefon, ketoconazole, miconazole, difenoconazole and prothioconazole) could lead to a better mechanism-based understanding of their embryotoxicity and pharmacological action. For evaluating embryotoxicity, we applied the total morphological scoring system (TMS) in embryos exposed for 48h...
March 3, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28263825/evaluation-of-the-risk-of-perchlorate-exposure-in-a-population-of-late-gestation-pregnant-women-in-the-united-states-application-of-probabilistic-biologically-based-dose-response-modeling
#13
A Lumen, N I George
The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure...
March 2, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28259702/in-vitro-cardiotoxicity-assessment-of-environmental-chemicals-using-an-organotypic-human-induced-pluripotent-stem-cell-derived-model
#14
Oksana Sirenko, Fabian A Grimm, Kristen R Ryan, Yasuhiro Iwata, Weihsueh A Chiu, Frederick Parham, Jessica A Wignall, Blake Anson, Evan F Cromwell, Mamta Behl, Ivan Rusyn, Raymond R Tice
An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28242323/arsenic-exposure-from-drinking-water-is-associated-with-decreased-gene-expression-and-increased-dna-methylation-in-peripheral-blood
#15
Syeda Shegufta Ameer, Karin Engström, Mohammad Bakhtiar Hossain, Gabriela Concha, Marie Vahter, Karin Broberg
BACKGROUND: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. OBJECTIVES: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. METHODS: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water...
February 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28242322/assessment-of-the-inhibitory-effects-of-pyrethroids-against-human-carboxylesterases
#16
Wei Lei, Dan-Dan Wang, Tong-Yi Dou, Jie Hou, Liang Feng, Heng Yin, Qun Luo, Jie Sun, Guang-Bo Ge, Ling Yang
Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids...
February 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28237878/a-tissue-dose-based-comparative-exposure-assessment-of-manganese-using-physiologically-based-pharmacokinetic-modeling-the-importance-of-homeostatic-control-for-an-essential-metal
#17
P Robinan Gentry, Cynthia Van Landingham, William G Fuller, Sandra I Sulsky, Tracy B Greene, Harvey J Clewell, Melvin E Andersen, Harry A Roels, Michael D Taylor, Athena M Keene
A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates...
February 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28237877/osimertinib-induces-autophagy-and-apoptosis-via-reactive-oxygen-species-generation-in-non-small-cell-lung-cancer-cells
#18
Zheng-Hai Tang, Wen-Xiang Cao, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells...
February 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28235556/relation-of-polymorphism-of-arsenic-metabolism-genes-to-arsenic-methylation-capacity-and-developmental-delay-in-preschool-children-in-taiwan
#19
Ru-Lan Hsieh, Chien-Tien Su, Horng-Sheng Shiue, Wei-Jen Chen, Shiau-Rung Huang, Ying-Chin Lin, Ming-I Lin, Shu-Chi Mu, Ray-Jade Chen, Yu-Mei Hsueh
Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital...
February 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28219650/dendritic-cells-death-induced-by-contact-sensitizers-is-controlled-by-nrf2-and-depends-on-glutathione-levels
#20
Zeina El Ali, Claudine Deloménie, Jérémie Botton, Marc Pallardy, Saadia Kerdine-Römer
Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action...
February 20, 2017: Toxicology and Applied Pharmacology
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