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Toxicology

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https://www.readbyqxmd.com/read/28645579/anti-androgenic-mechanisms-of-bisphenol-a-involve-androgen-receptor-signaling-pathway
#1
Hui Wang, Zhen Ding, Qiao-Mei Shi, Xing Ge, Heng-Xue Wang, Meng-Xue Li, Gang Chen, Qi Wang, Qiang Ju, Jin-Peng Zhang, Mei-Rong Zhang, Li-Chun Xu
We have shown Bisphenol A (BPA) acts as an androgen receptor (AR) antagonist in the previous study. However, the mechanisms underlying anti-androgenic effects of BPA remain unclear. The objective of this study was to explore whether the AR signaling was involved in AR antagonism of BPA. The Cell Counting Kit-8 (CCK-8) assay and Real-Time Cell Analysis (RTCA) iCELLigence system were applied to analyze the mouse Sertoli cell TM4 proliferation. The mammalian two-hybrid assays were performed to investigate the effects of BPA on the AR amino- and carboxyl-terminal regions (N/C) interaction and the interactions of the AR with steroid receptor coactivator-1 (SRC-1), co-repressors including silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (NCoR)...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645578/the-electrophilic-character-of-quinones-is-essential-for-the-suppression-of-bach1
#2
Chuanyang Su, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important cellular defense mechanisms against oxidative attack. BTB and CNC homology-1 (Bach1), like Kelch-like ECH-associated protein 1 (Keap1), is one of a negative regulator of Nrf2 that control antioxidant response elements (ARE)-dependent gene expressions. In the current study, we found that quinones show greater capacity than hydroquinones in nuclear Bach1 export, as well as ubiquitin-dependent Bach1 degradation in our experimental time frame...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645577/quantitative-structure-skin-permeability-relationships
#3
REVIEW
Ivanka Tsakovska, Ilza Pajeva, Merilin Al Sharif, Petko Alov, Elena Fioravanzo, Simona Kovarich, Andrew P Worth, Andrea-Nicole Richarz, Chihae Yang, Aleksandra Mostrag-Szlichtyng, Mark T D Cronin
This paper reviews in silico models currently available for the prediction of skin permeability. A comprehensive discussion on the currently available methods is presented, focusing on quantitative structure-permeability relationships. In addition, the mechanistic models and comparative studies that analyse different models are discussed. Limitations and strengths of the different approaches are highlighted together with the emergent issues and perspectives.
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#4
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#5
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28627408/developmental-exposure-to-glyphosate-based-herbicide-and-depressive-like-behavior-in-adult-offspring-implication-of-glutamate-excitotoxicity-and-oxidative-stress
#6
Daiane Cattani, Patrícia Acordi Cesconetto, Mauren Kruger Tavares, Eduardo Benedetti Parisotto, Paulo Alexandre De Oliveira, Carla Elise Heinz Rieg, Marina Concli Leite, Rui Daniel Schröder Prediger, Nestor Cubas Wendt, Guilherme Razzera, Danilo Wilhelm Filho, Ariane Zamoner
We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats...
June 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28627407/sources-mechanisms-and-consequences-of-chemical-induced-mitochondrial-toxicity
#7
EDITORIAL
Joel N Meyer, Sherine S L Chan
No abstract text is available yet for this article.
June 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28602540/deficiencies-in-mitochondrial-dynamics-sensitize-caenorhabditis-elegans-to-arsenite-and-other-mitochondrial-toxicants-by-reducing-mitochondrial-adaptability
#8
Anthony L Luz, Tewodros R Godebo, Latasha L Smith, Tess C Leuthner, Laura L Maurer, Joel N Meyer
Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1, PARK2) genes can cause human disease (collectively >1/10,000). Interestingly, however, the age of onset and severity of clinical manifestations varies greatly between patients with these diseases (even those harboring identical mutations), suggesting a role for environmental factors in the development and progression of certain mitochondrial diseases...
June 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28587785/dihydrotestosterone-as-mediator-for-cisplatin-induced-nephrotoxicity-new-insight-down-the-road
#9
LETTER
Amr Ahmed El-Arabey
No abstract text is available yet for this article.
June 3, 2017: Toxicology
https://www.readbyqxmd.com/read/28587784/gender-specific-expression-of-atp-binding-cassette-abc-transporters-and-cytoprotective-genes-in-mouse-choroid-plexus
#10
Katiria Flores, José E Manautou, J Larry Renfro
The choroid plexus (CP) and blood-brain barrier (BBB) control the movement of several drugs and endogenous compounds between the brain and systemic circulation. The multidrug resistance associated protein (Mrp) efflux transporters form part of these barriers. Several Mrp transporters are positively regulated by the transcription factor nuclear factor erythroid-2-related factor (Nrf2) in liver. The Mrps, Nrf2 and Nrf2-dependent genes are cytoprotective and our aim was to examine basal gender differences in expression of Mrp transporters, Nrf2 and Nrf2-dependent genes (Nqo1 and Ho-1) in the brain-barriers...
June 3, 2017: Toxicology
https://www.readbyqxmd.com/read/28587783/the-use-of-diacetyl-2-3-butanedione-and-related-flavoring-substances-as-flavorings-added-to-foods-workplace-safety-issues
#11
John B Hallagan
In 2001, staff of the National Institute of Occupational Safety and Health (NIOSH) identified diacetyl (2,3-butanedione) as a "marker" of exposure in a microwave popcorn manufacturing facility in which workers developed severe respiratory illness. Subsequent investigations identified additional workers in food and flavor manufacturing facilities also with severe respiratory illness. The flavor industry, NIOSH, and federal and state regulators conducted significant programs to address workplace safety concerns related to the manufacture of flavors and foods containing added flavors...
June 3, 2017: Toxicology
https://www.readbyqxmd.com/read/28578026/%C3%AE-pyrrolidinononanophenone-provokes-apoptosis-of-neuronal-cells-through-alterations-in-antioxidant-properties
#12
Toshiyuki Matsunaga, Yoshifumi Morikawa, Kyohei Kamata, Akinobu Shibata, Hidetoshi Miyazono, Yasuhide Sasajima, Koichi Suenami, Kiyohito Sato, Yuji Takekoshi, Satoshi Endo, Ossama El-Kabbani, Akira Ikari
In this study, we found that exposure to α-pyrrolidinononanophenone (α-PNP), a highly lipophilic synthetic cathinone, provokes apoptosis of human neuronal SK-N-SH cells. The drug sensitivity of the cells (50% lethal concentration of 12μM) was similar to those of aortic endothelial and smooth muscle cells, and was higher than those of cells derived from colon, liver, lung and kidney, suggesting that α-PNP overdose and abuse cause serious damage in central nervous and vascular systems. SK-N-SH cell treatment with lethal concentrations (20 and 50μM) of α-PNP facilitated the reactive oxygen species (ROS) production...
May 31, 2017: Toxicology
https://www.readbyqxmd.com/read/28572025/cobalt-toxicity-in-humans-a-review-of-the-potential-sources-and-systemic-health-effects
#13
REVIEW
Laura Leyssens, Bart Vinck, Catherine Van Der Straeten, Floris Wuyts, Leen Maes
Cobalt (Co) and its compounds are widely distributed in nature and are part of numerous anthropogenic activities. Although cobalt has a biologically necessary role as metal constituent of vitamin B12, excessive exposure has been shown to induce various adverse health effects. This review provides an extended overview of the possible Co sources and related intake routes, the detection and quantification methods for Co intake and the interpretation thereof, and the reported health effects. The Co sources were allocated to four exposure settings: occupational, environmental, dietary and medical exposure...
May 29, 2017: Toxicology
https://www.readbyqxmd.com/read/28572024/maternal-exposure-to-polybrominated-diphenyl-ether-bde-209-during-lactation-affects-germ-cell-survival-with-altered-testicular-glucose-homeostasis-and-oxidative-status-through-down-regulation-of-cx43-and-p27kip1-in-prepubertal-mice-offspring
#14
Debarshi Sarkar, Shio Kumar Singh
BDE-209, a congener of polybrominated diphenyl ethers (PBDEs), is mainly used as flame retardant and accounts for over 82% of total PBDE usage. PBDEs have recently been detected in human milk and cord blood. BDE-209 possesses weak estrogenic/anti-estrogenic properties and evokes hyperglycemia through impaired glucose homeostasis in rat liver. However, little is known of the effect of lactational exposure to BDE-209 on germ cell survival in relation to testicular glucose homeostasis, estradiol and oxidative status during prepubertal period...
May 29, 2017: Toxicology
https://www.readbyqxmd.com/read/28558994/ppar%C3%AE-independent-transcriptional-targets-of-perfluoroalkyl-acids-revealed-by-transcript-profiling
#15
Mitchell B Rosen, Kaberi P Das, John Rooney, Barbara Abbott, Christopher Lau, J Christopher Corton
Perfluoroalkyl acids (PFAAs) are ubiquitous and persistent environmental contaminants. Compounds such as perfluoroocanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) are readily found in the tissues of humans and wildlife. While PFOA and PFOS have been the subject of numerous studies since they were first described over a decade ago, less is known about the biological activity of PFHxS and PFNA. Most PFAAs are activators of peroxisome proliferator-activated receptor α (PPARα), although the biological effects of these compounds are likely mediated by other factors in addition to PPARα...
May 27, 2017: Toxicology
https://www.readbyqxmd.com/read/28552552/b-13-progenitor-derived-hepatocytes-b-13-h-cells-model-lipid-dysregulation-in-response-to-drugs-and-chemicals
#16
Alistair C Leitch, Philip M E Probert, James A Shayman, Stephanie K Meyer, George E N Kass, Matthew C Wright
Lipid dysregulation is a common hepatic adverse outcome after exposure to toxic drugs and chemicals. A donor-free rat hepatocyte-like (B-13/H) cell was therefore examined as an in vitro model for investigating mechanisms. The B-13/H cell irreversibly accumulated triglycerides (steatosis) in a time- and dose-dependent manner when exposed to fatty acids, an effect that was potentiated by the combined addition of hyperglycaemic levels of glucose and insulin. B-13/H cells also expressed the LXR nuclear receptors and exposure to their activators - T0901317 or GW3965 - induced luciferase expression from a transfected LXR-regulated reporter gene construct and steatosis in a dose-dependent manner with T0901317...
May 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28552422/8-methoxypsoralen-disrupts-mdr3-mediated-phospholipids-efflux-and-bile-acid-homeostasis-and-its-relevance-to-hepatotoxicity
#17
Guolin Zhao, Dengqiu Xu, Ziqiao Yuan, Zhenzhou Jiang, Wang Zhou, Zhijian Li, Mengyue Yin, Zhixing Zhou, Luyong Zhang, Tao Wang
Since its discovery in 1987, multidrug resistance 3 P-glycoprotein (MDR3) had recognized to play a crucial role in the translocation of phospholipids from the inner to outer leaflets of bile canalicular membranes. An increasing number of reports suggest that drug-mediated functional disruption of MDR3 is responsible for drug-induced cholestasis. 8-Methoxypsoralen (8-MOP) is used clinically to treat psoriasis, vitiligo and other skin disorders. However, psoralens safety for long-term use is a concern. In the current study, we evaluate 8-MOP's potential hepatotoxicity and effects on bile formation...
May 24, 2017: Toxicology
https://www.readbyqxmd.com/read/28549656/glycyrrhizin-and-glycyrrhetinic-acid-inhibits-alpha-naphthyl-isothiocyanate-induced-liver-injury-and-bile-acid-cycle-disruption
#18
Haina Wang, Zhong-Ze Fang, Ran Meng, Yun-Feng Cao, Naoki Tanaka, Kristopher W Krausz, Frank J Gonzalez
Alpha-naphthyl isothiocyanate (ANIT) is a common hepatotoxicant experimentally used to reproduce the pathologies of drug-induced liver injury in humans, but the mechanism of its toxicity remains unclear. To determine the metabolic alterations following ANIT exposure, metabolomic analyses was performed by use of liquid chromatography-mass spectrometry. Partial least squares discriminant analysis (PLS-DA) of liver, serum, bile, ileum, and cecum of vehicle- and ANIT-treated mice revealed significant alterations of individual bile acids, including increased tauroursodeoxycholic acid, taurohydrodeoxycholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid, and decreased ω-, β- and tauro-α/β- murideoxycholic acid, cholic acid, and taurocholic acid in the ANIT-treated groups...
May 23, 2017: Toxicology
https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#19
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10days...
May 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28529061/benzo-a-pyrene-7-8-diol-9-10-epoxide-suppresses-the-migration-and-invasion-of-human-extravillous-trophoblast-htr-8-svneo-cells-by-down-regulating-mmp2-through-inhibition-of-fak-src-pi3k-akt-pathway
#20
Rong Wang, Weiping Wang, Lin Ao, Zhi Wang, Xianglin Hao, Huidong Zhang
Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0μM BPDE for 24h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0...
May 18, 2017: Toxicology
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