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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/29782965/membrane-cholesterol-delays-cellular-apoptosis-induced-by-ginsenoside-rh2-a-steroid-saponin
#1
Sandrine L Verstraeten, Marie Albert, Adrien Paquot, Giulio G Muccioli, Donatienne Tyteca, Marie-Paule Mingeot-Leclercq
Saponins exhibit several biological and pharmacological activities, such as antibacterial, anti-inflammatory and anticancer effects. Many studies attribute their activities to their interactions with cholesterol. In this study, we focus on the steroid saponin ginsenoside Rh2, one of the active principles of Panax ginseng root. Some evidence suggests that lipid rafts, defined as nanodomains enriched in cholesterol and sphingolipids, could be involved in the Rh2-induced apoptosis. However, the role of membrane lipids, especially cholesterol, in this process is still poorly understood...
May 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29782964/an-in-vitro-approach-for-prioritization-and-evaluation-of-chemical-effects-on-glucocorticoid-receptor-mediated-adipogenesis
#2
Jessica K Hartman, Tyler Beames, Bethany Parks, Daniel Doheny, Gina Song, Alina Efremenko, Miyoung Yoon, Briana Foley, Chad Deisenroth, Patrick D McMullen, Rebecca A Clewell
Rising obesity rates worldwide have socio-economic ramifications. While genetics, diet, and lack of exercise are major contributors to obesity, environmental factors may enhance susceptibility through disruption of hormone homeostasis and metabolic processes. The obesogen hypothesis contends that chemical exposure early in development may enhance adipocyte differentiation, thereby increasing the number of adipocytes and predisposing for obesity and metabolic disease. We previously developed a primary human adipose stem cell (hASC) assay to evaluate the effect of environmental chemicals on PPARG-dependent adipogenesis...
May 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29782963/bet-inhibition-by-jq1-alleviates-streptozotocin-induced-diabetic-cardiomyopathy
#3
Miao Guo, Hong-Xia Wang, Wen-Jun Chen
Diabetic cardiomyopathy is a cascade of complex events leading to eventual heart failure in diabetes. JQ1, one of Bromodomain and extra-terminal domain (BET) protein inhibitors, has exerted therapeutic effects on cancer proliferation, inflammation and cardiovascular disease. Recently, JQ1 was reported to protect mice from bleomycin-induced lung fibrosis and reverse the fibrotic response in carbon tetrachloride-induced liver fibrosis. However, its role in diabetic cardiomyopathy remains to be clarified. Our results indicated that JQ1 treatment suppressed cardiac fibrosis and improved cardiac function in a STZ-induced diabetic mouse model...
May 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29782962/monosodium-glutamate-induced-nociception-and-oxidative-stress-dependent-on-time-of-administration-age-of-rats-and-susceptibility-of-spinal-cord-and-brain-regions
#4
Suzan Gonçalves Rosa, Pietro Maria Chagas, Ana Paula Pesarico, Cristina Wayne Nogueira
Monosodium glutamate (MSG), a food flavor enhancer used worldwide, has been studied because it may cause neurotoxicity, which is associated with oxidative stress. The aim of this study was to investigate whether spinal cord and brain regions are affected by oxidative stress and the temporal profile of nociceptive responses induced by MSG in newborn and adult rats. The newborn (post natal day, PND 1) Wistar rats received ten subcutaneous injections of MSG (4.0 g/kg) or saline solution. At PND 3, 11 or 90, the rats performed nociceptive tests and parameters of oxidative stress were evaluated in samples of spinal cord and brain regions...
May 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29778398/antipsychotic-induced-disorders-reported-cases-and-prospective-study-on-muscle-biomarkers-after-high-exposure-to-haloperidol
#5
Abderrezak Khelfi, Mohammed Azzouz, Rania Abtroun, Mohammed Reggabi, Berkahoum Alamir
Antipsychotic drugs are known to induce neuromuscular effects. In this study, we review 13 years (2002-2014) of antipsychotic intoxications reported by the anti-poisoning center of Algiers (APCA). The most recorded symptoms were neuromuscular/muscular disorders, of which haloperidol was the most inducer among all antipsychotics. A prospective study was conducted between December 2012 and January 2017 to evaluate muscle effects generated after intentional or accidental ingestion of haloperidol. Fifty-one patients admitted in different emergency departments in Algiers were included in this study...
May 17, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29777732/antinociceptive-effect-of-tadalafil-in-various-pain-models-involvement-of-opioid-receptors-and-nitric-oxide-cyclic-gmp-pathways
#6
Mohammad M Mehanna, Souraya Domiati, Hania Nakkash Chmaisse, Ahmed El Mallah
Nitric oxide has been proven to play an important role in nociception, accordingly, its promoters, phosphodiesterase inhibitors have been investigated as pain response modulators. Aiming to evaluate the central effect of tadalafil, a phosphodiesterase 5 inhibitor, and to determine its EC50, tail flick and hot plate tests were utilized. On the other hand, its nociceptive peripheral analgesic effect was assessed through acetic-acid induced writhing model. Formalin test was used to appraise both non-inflammatory and inflammatory pain responses...
May 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29775649/expression-and-function-of-tlr4-induced-b1r-bradykinin-receptor-on-cardiac-fibroblasts
#7
Claudia Muñoz-Rodríguez, Samuel Fernández, José Miguel Osorio, Francisco Olivares, Renatto Anfossi, Samir Bolivar, Claudio Humeres, Pía Boza, Raúl Vivar, Viviana Pardo-Jimenez, Karen E Hemmings, Neil A Turner, Guillermo Díaz-Araya
Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels...
May 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29775648/towards-a-quantitative-model-to-predict-the-toxicity-pathogenicity-potential-of-mineral-fibers
#8
Alessandro F Gualtieri
A number of mineral fibers represent a health hazard because they are classified as cancer-causing chemical/physical toxicants upon (chronic) dust inhalation. Although in the last decades they have been the subject of intensive multidisciplinary investigations, the mechanisms by which mineral fibers induce toxic and pathogenic adverse effects on human health and environment are not yet fully understood. The major intricacy of the biological approach that prevents the design of a conclusive shared model of behavior of mineral fibers in a biological system stems from their very nature with intrinsic variability in chemical, molecular, structural and morphometric parameters, biodurability and surface reactivity...
May 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29763636/inhibition-of-cox-2-mpges-1-and-5-lox-in-macrophages-by-leonurine-ameliorates-monosodium-urate-crystal-induced-inflammation
#9
Yanzhuo Liu, Chenfan Duan, Honglei Chen, Chenlong Wang, Xiaoxiao Liu, Miao Qiu, Honglin Tang, Feng Zhang, Xiaoyang Zhou, Jing Yang
Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase-1 (mPGES-1)-derived eicosanoids play an essential role in human inflammatory disorders. Here, we investigated whether inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate (MSU) crystal-induced inflammation. Virtual screening assay and in vitro enzyme inhibition assay showed that leonurine was a potential inhibitor of COX-2, mPGES-1 and 5-LOX. Compared with COX-2 inhibitor celecoxib, leonurine (30 mg/kg) significantly decreased ankle perimeter, gait score and neutrophil number in synovial fluid in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, mPGES-1 and 5-LOX and production of prostaglandin E2 (PGE2 ) and leukotriene B4 (LTB4 ) in the synovial fluid macrophages...
May 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29758222/differentiation-of-sow-and-mouse-ovarian-granulosa-cells-exposed-to-zearalenone-in-vitro-using-rna-seq-gene-expression
#10
Guo-Liang Zhang, Jun-Lin Song, Yi Zhou, Rui-Qian Zhang, Shun-Feng Cheng, Xiao-Feng Sun, Guo-Qing Qin, Wei Shen, Lan Li
Zearalenone (ZEA), a natural contaminant found in feed, has been shown to have a negative impact on domestic animal reproduction, particularly in pigs. There are species-specific differences in the ZEA-induced toxicity pattern. Here, we investigated the different biological effects of ZEA exposure on porcine and mouse granulosa cells, using RNA-seq analysis. We treated murine and porcine granulosa cells with 10 μM and 30 μM ZEA during 72 h of culturing, in vitro. The results showed that 10 μM ZEA exposure significantly altered mitosis associated genes in porcine granulosa cells, while the same treatment significantly altered the steroidogenesis associated genes in mouse granulosa cells...
May 11, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29753715/disposition-and-metabolism-of-the-bisphenol-analogue-bisphenol-s-in-harlan-sprague-dawley-rats-and-b6c3f1-n-mice-and-in-vitro-in-hepatocytes-from-rats-mice-and-humans
#11
Suramya Waidyanatha, Sherry R Black, Rodney W Snyder, Yun Lan Yueh, Vicki Sutherland, Purvi R Patel, Scott L Watson, Timothy R Fennell
With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [14 C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose...
May 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29753006/course-dose-and-stage-dependent-toxic-effects-of-prenatal-dexamethasone-exposure-on-long-bone-development-in-fetal-mice
#12
Ze Chen, Xin Zhao, Yunzepeng Li, Rui Zhang, Zaihui Nie, Xiang Cheng, Xianrong Zhang, Hui Wang
Dexamethasone is routinely used for treating those mothers at risk for preterm delivery. However, overexposure to exogenous glucocorticoids induces bone loss in offspring, and the "critical window" and safe dose of this treatment are largely unknown. In this study, we found that femoral length, and the length of the primary ossification center were significantly reduced in fetal mice after repeated prenatal dexamethasone exposure (PDE). Compared with single-course exposure on gestational day (GD)15, newborn mice with repeated PDE (3 times, from GD15 to 17) showed a significant decrease in femoral trabecular bone mass with decreased trabecular number and thickness...
May 9, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29753005/a-transcriptome-comparison-of-time-matched-developing-human-mouse-and-rat-neural-progenitor-cells-reveals-human-uniqueness
#13
Stefan Masjosthusmann, Daniel Becker, Barbara Petzuch, Jördis Klose, Clara Siebert, Rene Deenen, Marta Barenys, Jenny Baumann, Katharina Dach, Julia Tigges, Ulrike Hübenthal, Karl Köhrer, Ellen Fritsche
It is widely accepted that human brain development has unique features that cannot be represented by rodents. Obvious reasons are the evolutionary distance and divergent physiology. This might lead to false predictions when rodents are used for safety or pharmacological efficacy studies. For a better translation of animal-based research to the human situation, human in vitro systems might be useful. In this study, we characterize developing neural progenitor cells from prenatal human and time-matched rat and mouse brains by analyzing the changes in their transcriptome profile during neural differentiation...
May 9, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29753004/aggregate-exposure-of-the-adult-french-population-to-pyrethroids
#14
Keyvin Darney, Laurent Bodin, Michèle Bouchard, Jonathan Côté, Jean-Luc Volatier, Virginie Desvignes
The French Nutrition and Health Survey (ENNS) reported higher biomarker levels of exposure to pyrethroids than those observed in North American and German biomonitoring studies. The authors therefore investigated aggregate exposure to permethrin as an initial case study because this compound is one of the most widely-used pyrethroid insecticides. We assessed several contamination sources-such as indoor and outdoor air, settled dust and diet-and several pathways, including oral, inhalation and dermal routes...
May 9, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29751049/increased-butyrate-priming-in-the-gut-stalls-microbiome-associated-gastrointestinal-inflammation-and-hepatic-metabolic-reprogramming-in-a-mouse-model-of-gulf-war-illness
#15
Ratanesh Kumar Seth, Diana Kimono, Firas Alhasson, Sutapa Sarkar, Muayad Albadrani, Stephen K Lasley, Ronnie Horner, Patricia Janulecewicz, Mitzi Nagarkatti, Prakash Nagarkatti, Kimberly Sullivan, Saurabh Chatterjee
Most of the associated pathologies in Gulf War Illness (GWI) have been ascribed to chemical and pharmaceutical exposures during the war. Since an increased number of veterans complain of gastrointestinal (GI), neuroinflammatory and metabolic complications as they age and there are limited options for a cure, the present study was focused to assess the role of butyrate, a short chain fatty acid for attenuating GWI-associated GI and metabolic complications. Results in a GWI-mouse model of permethrin and pyridostigmine bromide (PB) exposure showed that oral butyrate restored gut homeostasis and increased GPR109A receptor copies in the small intestine (SI)...
May 8, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29751048/predicting-emp-hazard-lessons-from-studies-with-inhaled-fibrous-and-non-fibrous-nano-and-micro-particles
#16
Günter Oberdörster, Uschi Graham
Inhalation exposure to elongated cleavage fragments occurring at mineral and rock mining and crushing operations raises important questions regarding potential health effects given their resemblance to fibers with known adverse health effects like amphibole asbestos. Thus, a major goal for establishing a toxicity profile for elongate mineral particles (EMPs) is to identify and characterize a suspected hazard and characterize a risk by examining together results of hazard and exposure assessment. This will require not only knowledge about biokinetics of inhaled EMPs but also about underlying mechanisms of effects induced by retained EMPs...
May 8, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29738812/dosimetry-of-inhaled-elongate-mineral-particles-in-the-respiratory-tract-the-impact-of-shape-factor
#17
Bahman Asgharian, T Price Owen, Eileen D Kuempel, Annie M Jarabek
Inhalation exposure to some types of fibers (e.g., asbestos) is well known to be associated with respiratory diseases and conditions such as pleural plaques, fibrosis, asbestosis, lung cancer, and mesothelioma. In recent years, attention has expanded to other types of elongate mineral particles (EMPs) that may share similar geometry with asbestos fibers but which may differ in mineralogy. Inhalability, dimensions and orientation, and density are major determinants of the aerodynamic behavior for fibers and other EMPs; and the resultant internal dose is recognized as being the critical link between exposure and pathogenesis...
May 5, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29733868/investigation-of-belinostat-induced-genomic-instability-by-molecular-cytogenetic-analysis-and-pathway-focused-gene-expression-profiling
#18
S M Attia, M A Al-Hamamah, M R Alotaibi, G I Harisa, M M Attia, S F Ahmad, M A Ansari, A Nadeem, S A Bakheet
Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study...
May 4, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29730311/sodium-tanshinone-iia-sulfonate-promotes-endothelial-integrity-via-regulating-ve-cadherin-dynamics-and-rhoa-rock-mediated-cellular-contractility-and-prevents-atorvastatin-induced-intracerebral-hemorrhage-in-zebrafish
#19
Zhong-Yan Zhou, Bin Huang, Shang Li, Xiao-Hui Huang, Jing-Yi Tang, Yiu Wa Kwan, Pui Man Hoi, Simon Ming-Yuen Lee
Impaired vascular integrity leads to serious cerebral vascular diseases such as intracerebral hemorrhage (ICH). In addition, high-dose statin therapy is suggested to cause increased ICH risk due to unclear effects of general inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) on the vascular system. Here we evaluated the protective effects of sodium tanshinone IIA sulfonate (STS), which has high efficacy and safety in clinical studies of ischemic stroke, by using atorvastatin (Ator) induced ICH zebrafish embryos and human umbilical vein endothelial cells (HUVECs)...
May 3, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29730310/analysis-and-identification-of-elongated-mineral-particles-in-road-coated-aggregates
#20
Erell Leocat, Christophe Rielland, Aurélien Urvoy, Patrice Letessier
The issue of Elongated Mineral Particles (EMP) in building materials has been revealed during roadworks in 2013 in France. In fact, road coating aggregates are made of specific rock gravels that can contain Naturally Occurring Asbestos (NOA), which is mainly actinolite. The legislation refers to six regulatory asbestos, that consist in asbestiform habitus of the six minerals. The current technical standard is not adapted for analyzing natural material, as it cannot distinguish the asbestiform fibers and the cleavage fragments fibers...
May 3, 2018: Toxicology and Applied Pharmacology
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