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Toxicology

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https://www.readbyqxmd.com/read/29154944/%C3%AE-estradiol-antagonizes-the-inhibitory-effects-of-caffeine-in-bmmscs-via-the-er%C3%AE-mediated-camp-dependent-pka-pathway
#1
Chaowei Wang, Yi Zhou, Xiaoxu Guan, Mengfei Yu, Huiming Wang
Caffeine negatively mediates bone homeostasis to cause bone loss and even osteoporosis. This phenomenon occurs in postmenopausal women with estrogen deficiency but not in healthy young women. In this study, we determined whether the effects of caffeine on bone homeostasis were antagonized by estrogen and the underlying mechanisms. In particular, because high levels of cAMP, an important second messenger, have been observed in postmenopausal women suffering from osteoporosis, we examined the role of cAMP in the effects of caffeine on bone homeostasis...
November 15, 2017: Toxicology
https://www.readbyqxmd.com/read/29104120/methylmercury-exposure-causes-a-persistent-inhibition-of-myogenin-expression-and-c2c12-myoblast-differentiation
#2
Lisa M Prince, Matthew D Rand
Methylmercury (MeHg) is a ubiquitous environmental toxicant, best known for its selective targeting of the developing nervous system. MeHg exposure has been shown to cause motor deficits such as impaired gait and coordination, muscle weakness, and muscle atrophy, which have been associated with disruption of motor neurons. However, recent studies have suggested that muscle may also be a target of MeHg toxicity, both in the context of developmental myogenic events and of low-level chronic exposures affecting muscle wasting in aging...
November 15, 2017: Toxicology
https://www.readbyqxmd.com/read/29154799/integrative-omics-data-analyses-of-repeated-dose-toxicity-of-valproic-acid-in-vitro-reveal-new-mechanisms-of-steatosis-induction
#3
Simone G J van Breda, Sandra M H Claessen, Marcel van Herwijnen, Daniël H J Theunissen, Danyel G J Jennen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HDAC inhibiting properties, which may cause steatosis in the liver. The present study investigates the effect of repetitive VPA treatment of primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of VPA for 5days daily which induced lipid accumulation. Part of the PHH was left untreated for 3days for studying the persistence of 'omics' changes...
November 14, 2017: Toxicology
https://www.readbyqxmd.com/read/29141199/disruption-of-mitochondrial-function-as-mechanism-for-anti-cancer-activity-of-a-novel-mitochondriotropic-menadione-derivative
#4
José Teixeira, Ricardo Amorim, Katia Santos, Pedro Soares, Sandipan Datta, Gino A Cortopassi, Teresa L Serafim, Vilma A Sardão, Jorge Garrido, Fernanda Borges, Paulo J Oliveira
Menadione, also known as vitamin K3, is a 2-methyl-1,4 naphthoquinone with a potent cytotoxic activity mainly resulting from its quinone redox-cycling with production of reactive oxygen species (ROS). Although increased ROS generation is considered a relevant mechanism in cancer cell death, it may not be sufficiently effective to kill cancer cells due to phenotypic adaptations. Therefore, combining ROS-generating agents with other molecules targeting important cancer cell phenotypes can be an effective therapeutic strategy...
November 12, 2017: Toxicology
https://www.readbyqxmd.com/read/29129815/biological-effects-of-adipocytes-in-sulfur-mustard-induced-toxicity
#5
Hua Xu, Zhongcai Gao, Peng Wang, Bin Xu, Yajiao Zhang, Long Long, Cheng Zong, Lei Guo, Weijian Jiang, Qinong Ye, Lili Wang, Jianwei Xie
Sulphur mustard (2,2'-dichloroethyl sulfide; SM) is a vesicant chemical warfare agent whose mechanism of acute or chronic action is not known with any certainty and to date there is no effective antidote. SM accumulation in adipose tissue (AT) has been originally verified in our previous study. To evaluate the biological effect caused by the presence of abundant SM in adipocyte and assess the biological role of AT in SM poisoning, in vitro and in vivo experiments were performed. High content analysis revealed multi-cytotoxicity in SM exposed cells in a time and dose dependent manner, and adipocytes showed a relative moderate damage compared with non-adipocytes...
November 10, 2017: Toxicology
https://www.readbyqxmd.com/read/29129814/zinc-deficiency-promotes-cystitis-related-bladder-pain-by-enhancing-function-and-expression-of-cav3-2-in-mice
#6
Tomoka Ozaki, Junki Matsuoka, Maho Tsubota, Shiori Tomita, Fumiko Sekiguchi, Takeshi Minami, Atsufumi Kawabata
Cav3.2 T-type Ca(2+) channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Cav3.2, and enhanced by H2S that interacts with zinc. Cav3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Cav3.2 activity by H2S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Cav3...
November 10, 2017: Toxicology
https://www.readbyqxmd.com/read/29128272/cytoprotection-of-lipoic-acid-against-toxicity-induced-by-saxitoxin-in-hippocampal-cell-line-ht-22-through-in-silico-modeling-and-in-vitro-assays
#7
Patrícia Ramos, Marcos Schmitz, Sibele Gama, Aline Portantiolo, Michael Gonzalez Durruthy, Ana Paula de Souza Votto, Luisa Rodrigues Cornetet, Karina Dos Santos Machado, Adriano Wehrli, Mariana Zancan Tonel, Solange Binotto Fagan, João Sarkis Yunes, José Maria Monserrat
Saxitoxins (STXs) are potent neurotoxins that block voltage-gated channels in neurons and induce cytotoxicity. These toxins not only can generate reactive oxygen species but also can alter antioxidant levels, promoting oxidative stress. Under this pro-oxidant situation, the use of the antioxidant lipoic acid (LA) can represent a chemoprotective alternative to minimize the deleterious effects induced by neurotoxins as STXs. P-glycoprotein (P-gp) is a well-known ATP-binding cassette (ABC) transporter that plays a crucial role in the extrusion of toxic substances, decreasing their accumulation and potential intracellular effects in virtue of its broad substrate specificity, its expression in many excretory tissues and its large efflux capacity...
November 8, 2017: Toxicology
https://www.readbyqxmd.com/read/29127035/the-high-production-volume-fungicide-pyraclostrobin-induces-triglyceride-accumulation-associated-with-mitochondrial-dysfunction-and-promotes-adipocyte-differentiation-independent-of-ppar%C3%AE-activation-in-3t3-l1-cells
#8
Anthony L Luz, Christopher D Kassotis, Heather M Stapleton, Joel N Meyer
Pyraclostrobin is one of the most heavily used fungicides, and has been detected on a variety of produce, suggesting human exposure occurs regularly. Recently, pyraclostrobin exposure has been linked to a variety of toxic effects, including neurodegeneration and triglyceride (TG) accumulation. As pyraclostrobin inhibits electron transport chain complex III, and as mitochondrial dysfunction is associated with metabolic syndrome (cardiovascular disease, type II diabetes, obesity), we designed experiments to test the hypothesis that mitochondrial dysfunction underlies its adipogenic activity...
November 7, 2017: Toxicology
https://www.readbyqxmd.com/read/29127034/balancing-nanotoxicity-and-returns-in-health-applications-the-prisoner-s-dilemma
#9
D A Gkika, L Magafas, P Cool, J Braet
Over the past 30 years, there have been significant advancements in the field of nanomaterials. The possibility to use them in applications such as cancer treatment is extremely promising; however, the toxicity of many nanomaterials as well as the high costs associated with their use is still a concern. This paper aims to study the connection between nanomaterial toxicity and cost. This synergy may be interpreted as a different version of the classic "Prisoner's Dilemma" game, which in this case attempts to explain the possible outcomes of cooperation versus conflict between science advocating for the use of high-risk, possibly toxic materials due to their high returns, and society that might be dubious about the use of high-risk materials...
November 7, 2017: Toxicology
https://www.readbyqxmd.com/read/29127033/the-role-of-tgf%C3%AE-receptor-1-smad3-signaling-in-regulating-the-osteoclastic-mode-affected-by-fluoride
#10
Haolan Yu, Ningning Jiang, XiuHua Yu, Zhitao Zhao, Xiuyun Zhang, Hui Xu
Studies that have focused on the role TGFβ signaling plays in osteoclast activity are gradually increasing; however, literature is rare in terms of fluorosis. The aim of this study is to observe the role the TβR1/Smad3 pathway plays in fluoride regulating cellsosteoclast-like cells that are under the treatment of TGFβ receptor 1 kinase. The RANKL-mediated osteoclast-like cells from RAW264.7 cells were used as osteoclast precursor model. The profile of miRNA expression in fluoride-treated osteoclast-like cells exhibited 303 upregulated miRNAs, 61 downregulated miRNAs, and further drew 37 signaling pathway maps by KEGG and Biocarta pathway enrichment analysis...
November 7, 2017: Toxicology
https://www.readbyqxmd.com/read/29113834/aflatoxin-b1-impairs-sperm-quality-and-fertilization-competence
#11
A Komsky-Elbaz, M Saktsier, Z Roth
Aflatoxins are poisonous byproducts of the soilborne fungus Aspergillus, involved in the decomposition of plant materials. Aflatoxins can be found in various food products, such as maize, sorghum, millet, rice and wheat. AFB1 is the most toxic of these, classified as a carcinogen and mutagen for both humans and animals. AFB1 has been detected in human cord blood and placenta; however, its toxic effect on sperm is less known. The current study examines sperm responses associated with AFB1 exposure. These included acrosome integrity and function, mitochondrial polarity, DNA fragmentation, fertilization competence and early embryonic development...
November 4, 2017: Toxicology
https://www.readbyqxmd.com/read/29113833/the-role-of-genetic-background-in-susceptibility-to-chemical-warfare-nerve-agents-across-rodent-and-non-human-primate-models
#12
REVIEW
Liana M Matson, Hilary S McCarren, C Linn Cadieux, Douglas M Cerasoli, John H McDonough
Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies...
November 4, 2017: Toxicology
https://www.readbyqxmd.com/read/29108743/differentially-dna-methylation-changes-induced-in-vitro-by-traffic-derived-nanoparticulate-matter
#13
Xiaoning Lei, Joshua E Muscat, Bo Zhang, Xuyang Sha, Guangli Xiu
The cytotoxicity, apoptosis, reactive oxygen species (ROS) and DNA damage induced by the commercial diesel exhaust particulate matter (PM) (SRM2975) with concentrations ranging from 0.1μg·mL(-1) to 20μg·mL(-1) were assessed in human umbilical vein endothelial cells (HUVECs) in vitro. An epigenetics-wide investigation of DNA methylation profiles was also performed using a new methylation beadchip (Illumina 850K) to identify the health effects of traffic-derived nanoparticulate matter (nPM) with a concentration of 20μg·mL(-1)...
November 3, 2017: Toxicology
https://www.readbyqxmd.com/read/29108742/gene-expression-analysis-reveals-chronic-low-level-exposure-to-the-pesticide-diazinon-affects-psychological-disorders-gene-sets-in-the-adult-rat
#14
Claire Y Savy, Ann E Fitchett, Peter G Blain, Christopher M Morris, Sarah J Judge
Chronic low level exposure to organophosphate (OPs) pesticides in adulthood has been linked to adverse neurobehavioural deficits and psychological disorder symptoms, although this remains a contentious issue. The OP-induced biological changes that could underlie these effects are unclear. We assessed gene expression changes following chronic low level exposure to diazinon, a pesticide with a high dietary exposure risk. Adult male rats were orally exposed to diazinon (0, 1, 2mg/kg, 5days a week for 12 weeks)...
November 3, 2017: Toxicology
https://www.readbyqxmd.com/read/29102675/rna-seq-revealed-atf3-regulated-inflammation-induced-by-silica
#15
Judy Y W Chan, Joseph C C Tsui, Patrick T W Law, Winnie K W So, Doris Y P Leung, Michael M K Sham, Stephen K W Tsui, Carmen W H Chan
BACKGROUND: Millions of workers are exposed to dust containing silica. Chronic and over-exposure to silica will lead to silicosis, which is an irreversible and sometimes fatal lung disease. The disordered physiological processes of silicosis consist of accumulation of silica particles in the alveoli of the lung. Then, the ingestion of the silica particles by macrophages was followed by an inflammatory response. Up till now, the chest radiographs remain the key tool in diagnosing and assessing the extent of silicosis...
November 2, 2017: Toxicology
https://www.readbyqxmd.com/read/29100879/applicability-of-an-integrated-testing-strategy-consisting-of-in-silico-in-chemico-and-in-vitro-assays-for-evaluating-the-skin-sensitization-potencies-of-isocyanates
#16
Toshiyuki Ohtake, Yosuke Maeda, Tae Hayashi, Hidenori Yamanaka, Makoto Nakai, Masahiro Takeyoshi
The skin sensitization potential of chemicals has been traditionally assessed using regulatory accepted in vivo methods, such as guinea pig maximization test or mouse local lymph node assays (LLNAs). A huge effort to reduce and replace the use of animals for safety assessments of chemicals because of regulatory requirements and ethical issues is presently underway, and alternative non-animal methods have been greatly developed. So far, a few studies have investigated the sensitization potencies of isocyanates which is a group of highly reactive chemicals that are known to be occupational allergens...
November 1, 2017: Toxicology
https://www.readbyqxmd.com/read/29100878/n-acetyl-l-cysteine-and-mn-2-attenuate-cd-2-induced-disturbance-of-the-intracellular-free-calcium-homeostasis-in-cultured-cerebellar-granule-neurons
#17
Nickolay K Isaev, Svetlana Avilkina, Sergey A Golyshev, Elisaveta E Genrikhs, Olga P Alexandrova, Marina R Kapkaeva, Elena V Stelmashook
Cadmium is a highly toxic heavy metal that is capable of accumulating in the body via direct exposure or through the alimentary and respiratory tract, leading to neurodegeneration. In this article, we show that the application of CdCl2 (0.001-0.005mM) for 48h induced high dose-dependent death rate of cultured cerebellar granule neurons (CGNs). Unlike Trolox or vitamin E, antioxidant N-acetyl-l-cysteine (NAC, 1mM) and Mn(2+) (0.0025-0.005mM) significantly protected CGNs from this toxic effect. Using Fluo-4 AM, measurements of intracellular calcium ions demonstrated that 24h-exposure to Cd(2+) induced intensive increase of Fluo-4 fluorescence in neurons accompanied by mitochondria swelling...
October 31, 2017: Toxicology
https://www.readbyqxmd.com/read/29111403/the-critical-role-of-autophagy-in-cadmium-induced-immunosuppression-regulated-by-endoplasmic-reticulum-stress-mediated-calpain-activation-in-raw264-7-mouse-monocytes
#18
Keum-Young So, Byung-Hoon Lee, Seon-Hee Oh
Cadmium (Cd) has toxic and suppressive effects on the immune system, but the underlying mechanisms remain poorly understood. Here, we show that autophagy plays a critical role in regulation of Cd-induced immunosuppression in RAW264.7 cells. Cd decreased cell viability in a dose-dependent manner; cleaved caspase-8, caspase-3, and poly (ADP-ribose) polymerase (PARP)-1; increased DNA laddering; induced CCAAT-enhancer-binding protein homologous protein (CHOP); and reduced tumor necrosis factor (TNF)-α expression; indicating that caspase-dependent and endoplasmic reticulum (ER)-mediated apoptosis are involved in Cd-induced immunotoxicity...
October 27, 2017: Toxicology
https://www.readbyqxmd.com/read/29079364/assessment-of-metal-sensitizer-potency-with-the-reconstructed-human-epidermis-il-18-assay
#19
Susan Gibbs, Ilona Kosten, Rosalien Veldhuizen, Sander Spiekstra, Emanuela Corsini, Erwin Roggen, Thomas Rustemeyer, Albert J Feilzer, Cees J Kleverlaan
According to the new EU Medical Devices (MDR) legislation coming into effect in 2017, manufactures will have to comply with higher standards of quality and safety for medical devices in order to meet common safety concerns regarding such products. Metal alloys are extensively used in dentistry and medicine (e.g. orthopedic surgery and cardiology) even though clinical experience suggests that many metals are sensitizers. The aim of this study was to further test the applicability domain of the in vitro reconstructed human epidermis (RhE) IL-18 assay developed to identify contact allergens and in doing so: i) determine whether different metal salts, representing leachables from metal alloys used in medical devices, could be correctly labelled and classified; and ii) assess the ability of different salts for the same metal to penetrate the skin stratum corneum...
October 25, 2017: Toxicology
https://www.readbyqxmd.com/read/29079363/receptor-partial-agonism-and-method-to-express-receptor-partial-activation-with-respect-to-novel-full-logistic-model-of-mixture-toxicology
#20
Martin Ezechiáš, Tomáš Cajthaml
Living organisms interact with various chemical compounds via receptors, which is described by the receptor theory. The affinity of the biologically active compounds toward receptors and their ability to trigger a biological or toxic signal vary substantially. In this work, we describe a new insight into understanding of the mode of action of receptor partial agonists and the receptor theory using a Full Logistic Model (FLM) of mixture toxicology. We describe the hypothesis that the effect of a partial agonist can be mathematically described via separation of agonistic and antagonistic behavior of the partial agonist where the antagonistic effect is described as an action of the compound producing zero effect...
October 25, 2017: Toxicology
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