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Toxicology

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https://www.readbyqxmd.com/read/28089772/anxiety-like-behavior-due-to-perinatal-exposure-to-bisphenol-a-is-associated-with-decrease-in-excitatory-to-inhibitory-synaptic-density-of-male-mouse-brain
#1
Dhiraj Kumar, M K Thakur
Bisphenol-A (BPA) is a synthetic endocrine disruptor which causes anxiety like behavior in rodents, though the underlying mechanism is not clearly understood. As excitatory-inhibitory synaptic proteins are the key regulators of anxiety, we have examined the effect of perinatal exposure to BPA on this behavior and the expression of excitatory (PSD95), inhibitory (gephyrin) and presynaptic density marker (synaptophysin) proteins in cerebral cortex and hippocampus of 3 and 8 weeks postnatal male mice. In open field (OF) test, BPA exposure reduced the time spent, number of entries and distance travelled in the central zone as compared to control in 8 weeks mice...
January 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#2
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28087464/mitochondrial-reactive-oxygen-species-regulate-fungal-protease-induced-inflammatory-responses
#3
Yun Hee Kim, Seung-Hyo Lee
Epidemiological studies have shown that fungal infections are a main cause of respiratory tract diseases, such as asthma, bronchopneumonia, intoxication, and invasive fungal disease. Fungi such as Aspergillus and Candida species have become increasingly important pathogens as the global climate changes. Accordingly, in this study, we evaluated the toxicological potential of Aspergillus protease in the lower respiratory tract. Exposure of Aspergillus protease to A549 cells induced upregulation of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 mRNAs and increased production of interleukin (IL)-8 and MCP-1 protein through enhanced mitochondrial reactive oxygen species (ROS) generation and activation of mitogen-activated protein kinase (MAPK) and activator protein (AP)-1...
January 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28082111/protective-effects-of-dioscin-against-doxorubicin-induced-nephrotoxicity-via-adjusting-fxr-mediated-oxidative-stress-and-inflammation
#4
Yimeng Zhang, Youwei Xu, Yan Qi, Lina Xu, Shasha Song, Lianhong Yin, Xufeng Tao, Yuhong Zhen, Xu Han, Xiaodong Ma, Kexin Liu, Jinyong Peng
Dioscin shows active effects against renal ischemia/reperfusion injury and lipopolysaccharide-induced inflammatory kidney injury, however, little is known concerning the role of it on doxorubicin (Dox)-induced nephrotoxicity. In the present study, in vivo test of Dox-induced nephrotoxicity in rats and in vitro model in NRK-52E cells were developed. The results showed that dioscin significantly attenuated cell injury, obviously reduced ROS level in vitro, and markedly decreased the levels of BUN, Cr, MDA, and notably increased the levels of SOD, GSH and GSH-Px in rats...
January 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28082110/novel-phototoxicity-assay-using-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#5
Takashi Mori, Kiyoshi Higashi, Tokushige Nakano, Satoshi Ando, Atsushi Kuwahara, Noriyuki Suzuki, Koichi Saito
Some chemicals are harmful in to light-exposed tissues such as skin and eyes. The 3T3 Neutral Red Uptake Phototoxicity Test has been validated and adopted by the Organization of Economic and Community Development (OECD) as a method of evaluating chemical phototoxicity using mouse 3T3 fibroblasts. However, the high rate of false positive results associated with this test eventually led to increased laboratory animal usage. Although the eye is vulnerable to light damage because of constant exposure to environmental radiation, few approaches are available to predict ocular phototoxicity in humans...
January 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28082109/1-3-butadiene-induced-mitochondrial-dysfunction-is-correlated-with-mitochondrial-cyp2e1-activity-in-collaborative-cross-mice
#6
Jessica H Hartman, Grover P Miller, Andres A Caro, Stephanie D Byrum, Lisa M Orr, Samuel G Mackintosh, Alan J Tackett, Lee Ann MacMillan-Crow, Lance M Hallberg, Bill T Ameredes, Gunnar Boysen
Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight hydrophobic compounds, including 1,3-butadiene, which is converted by CYP2E1 to electrophilic epoxide metabolites that covalently modify cellular proteins and DNA. Previous CYP2E1 studies have mainly focused on the enzyme localized in the endoplasmic reticulum (erCYP2E1); however, active CYP2E1 also localizes in mitochondria (mtCYP2E1) and the distribution of CYP2E1 between organelles can influence an individual's response to exposure. Relatively few studies have focused on the contribution of mtCYP2E1 to activation of chemical toxicants...
January 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28069514/increased-microrna-21-expression-contributes-to-arsenic-induced-skin-lesions-skin-cancers-and-respiratory-distress-in-chronically-exposed-individuals
#7
Nilanjana Banerjee, Apurba K Bandyopadhyay, Suman Dutta, Jayanta K Das, Tarit Roy Chowdhury, Arun Bandyopadhyay, Ashok K Giri
More than 26 million people in West Bengal, India, are exposed to arsenic through drinking water, leading to several deleterious endpoints including precancerous and cancerous skin lesions and other non-dermatological health effects. Here, our aim was to identify whether miR21 is associated with such dermatological and non-dermatological health outcomes in chronically exposed humans. A total of 123 subjects from West Bengal were recruited for this study (45 exposed individuals with skin lesions, 38 exposed individuals without skin lesions and 40 unexposed individuals)...
January 6, 2017: Toxicology
https://www.readbyqxmd.com/read/28065592/comparison-of-fluorescence-based-methods-to-determine-nanoparticle-uptake-by-phagocytes-and-non-phagocytic-cells-in-vitro
#8
Meindl Claudia, Öhlinger Kristin, Ober Jennifer, Roblegg Eva, Fröhlich Eleonore
At many portals of entry the relative uptake by phagocytes and non-phagocytic cells has a prominent effect on availability and biological action of nanoparticles (NPs). Cellular uptake can be determined for fluorescence-labeled NPs. The present study compares three methods (plate reader, flow cytometry and image analysis) in order to investigate the influence of particle size and functionalization and medium content on cellular uptake of fluorescence-labeled polystyrene particles and to study the respective method́s suitability for uptake studies...
January 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28063906/pyrazinamide-induced-hepatotoxicity-is-alleviated-by-4-pba-via-inhibition-of-the-perk-eif2%C3%AE-atf4-chop-pathway
#9
Hong-Li Guo, Hozeifa M Hassan, Ping-Ping Ding, Shao-Jie Wang, Xi Chen, Tao Wang, Li-Xin Sun, Lu-Yong Zhang, Zhen-Zhou Jiang
Pyrazinamide (PZA)-induced serious liver injury, but the exact mechanism of PZA-induces hepatotoxicity remains controversial. Endoplasmic reticulum (ER) stress-caused cell apoptosis plays a critical role in the development of drug-induced liver injury (DILI). However, the direct connection between PZA toxicity and ER stress is unknown. In this study, we describe the role of ER stress in PZA induced hepatotoxicity in vivo and in vitro. We found that PZA induces apoptosis in HepG2 cells, and causes liver damage in rats, characterized by increased serum ALT, AST and TBA levels...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28063905/trichloroethylene-induced-formic-aciduria-in-the-male-c57-bl-6-mouse
#10
Edward A Lock, Paul Keane, Philip H Rowe, John R Foster, Daniel Antoine, Christopher M Morris
1, 1, 2-Trichloroethylene (TCE) is of environmental concern, due to evaporation while handling, chemical processing and leakage from chemical waste sites, leading to its contamination of ground water and air. For several decades there has been issues about possible long term health effects of TCE but recently the International Agency for Research on Cancer (IARC) and the US Environmental Protection Agency classified TCE as a human carcinogen. Links having been established between occupational exposures and kidney cancer and possible links to non-Hodgkin lymphoma and liver cancer, but there is more still more to learn...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28049045/in-vitro-models-reveal-differences-in-the-developmental-neurotoxicity-of-an-environmental-polycylic-aromatic-hydrocarbon-mixture-compared-to-benzo-a-pyrene-neuronotypic-pc12-cells-and-embryonic-neural-stem-cells
#11
Theodore A Slotkin, Samantha Skavicus, Jennifer Card, Richard T Di Giulio, Frederic J Seidler
In addition to their carcinogenic activity, polycyclic aromatic hydrocarbons (PAHs) are suspected to be developmental neurotoxicants. We evaluated the effects of PAHs with two in vitro models that assess distinct "decision nodes" in neurodifferentiation: neuronotypic PC12 cells, which characterize the transition from cell replication to neurodifferentiation, neurite outgrowth and neurotransmitter specification; and embryonic neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28049044/lymphocytes-contribute-to-biliary-injury-and-fibrosis-in-experimental-xenobiotic-induced-cholestasis
#12
Nikita Joshi, Anna K Kopec, Holly Cline-Fedewa, James P Luyendyk
The etiology of chronic bile duct injury and fibrosis in patients with autoimmune cholestatic liver diseases is complex, and likely involves immune cells such as lymphocytes. However, most models of biliary fibrosis are not autoimmune in nature. Biliary fibrosis can be induced experimentally by prolonged exposure of mice to the bile duct toxicant alpha-naphthylisothiocyanate (ANIT). We determined whether lymphocytes contributed to ANIT-mediated biliary hyperplasia and fibrosis in mice. Hepatic accumulation of T-lymphocytes and increased serum levels of anti-nuclear-autoantibodies were evident in wild-type mice exposed to ANIT (0...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28049043/perfluoroalkyl-acids-induced-liver-steatosis-effects-on-genes-controlling-lipid-homeostasis
#13
Kaberi P Das, Carmen R Wood, Mimi J Lin, Anatoly A Starkov, Christopher Lau, Kendall B Wallace, J Christopher Corton, Barbara D Abbott
Persistent presence of perfluoroalkyl acids (PFAAs) in the environment is due to their extensive use in industrial and consumer products, and their slow decay. Biochemical tests in rodent demonstrated that these chemicals are potent modifiers of lipid metabolism and cause hepatocellular steatosis. However, the molecular mechanism of PFAAs interference with lipid metabolism remains to be elucidated. Currently, two major hypotheses are that PFAAs interfere with mitochondrial beta-oxidation of fatty acids and/or they affect the transcriptional activity of peroxisome proliferator-activated receptor α (PPARα) in liver...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28049042/aryl-hydrocarbon-receptor-activation-by-2-3-7-8-tetrachlorodibenzo-p-dioxin-impairs-human-b-lymphopoiesis
#14
Jinpeng Li, Ashwini S Phadnis-Moghe, Robert B Crawford, Norbert E Kaminski
The homeostasis of peripheral B cell compartment requires lifelong B lymphopoiesis from hematopoietic stem cells (HSC). As a result, the B cell repertoire is susceptible to disruptions of hematopoiesis. Increasing evidence, primarily from rodent models, shows that the aryl hydrocarbon receptor (AHR) regulates hematopoiesis. To study the effects of persistent AHR activation on human B cell development, a potent AHR agonist and known environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was utilized...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28013001/mitochondrial-functions-of-thp-1-monocytes-following-the-exposure-to-selected-natural-compounds
#15
Nadin Schultze, Heike Wanka, Paula Zwicker, Ulrike Lindequist, Beate Haertel
The immune system is an important target of various xenobiotics, which may lead to severe adverse effects including immunosuppression or inappropriate immunostimulation. Mitochondrial toxicity is one possibility by which xenobiotics exert their toxic effects in cells or organs. In this study, we investigated the impact of three natural compounds, cyclosporine A (CsA), deoxynivalenol (DON) and cannabidiol (CBD) on mitochondrial functions in the THP-1 monocytic cell line. The cells were exposed for 24h to two different concentrations (IC10 and IC50 determined by MTT) of each compound...
December 21, 2016: Toxicology
https://www.readbyqxmd.com/read/27989758/low-level-of-mono-2-ethylhexyl-phthalate-reduces-oocyte-developmental-competence-in-association-with-impaired-gene-expression
#16
D Kalo, Z Roth
Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are reproductive toxicants. However, disruptive effects of MEHP at low concentrations on the oocyte and developing blastocyst are unknown. Previously, we detected low levels of MEHP in follicular fluid aspirated from DEHP-treated cows associated with reduced estradiol levels. Moreover, the MEHP concentrations found were similar to those reported for follicular fluid aspirated from women who have undergone IVF cycles...
December 15, 2016: Toxicology
https://www.readbyqxmd.com/read/27940129/a-systematic-meta-analysis-on-the-efficacy-of-pre-clinically-tested-nephroprotectants-at-preventing-aminoglycoside-nephrotoxicity
#17
REVIEW
Laura Vicente-Vicente, Alfredo G Casanova, María Teresa Hernández-Sánchez, Moisés Pescador, Francisco J López-Hernández, Ana Isabel Morales
Nephrotoxicity limits the use of aminoglycoside antibiotics. Kidney damage is produced mainly in the renal tubule due to an inflammatory and oxidative process. At preclinical level, many drugs and natural products have been tested as prospective protectors of aminoglycoside nephrotoxicity. The main objective of this work was to make a systematic literature review of preclinical studies about aminoglycoside nephrotoxicity protection and a statistical analysis based on the meta-analysis methodology. Studies published up to January 2016 were identified...
December 8, 2016: Toxicology
https://www.readbyqxmd.com/read/27932249/toxicologic-effects-of-28-day-dietary-exposure-to-the-flame-retardant-1-2-dibromo-4-1-2-dibromoethyl-cyclohexane-tbech-in-f344-rats
#18
Ivan H A Curran, Virginia Liston, Andrée Nunnikhoven, Don Caldwell, Matthew J S Scuby, Peter Pantazopoulos, Dorothea F K Rawn, Laurie Coady, Cheryl Armstrong, David E Lefebvre, Genevieve S Bondy
The brominated flame retardant TBECH is used as an additive to delay ignition and inhibit fires in construction materials and consumer goods. Trends in human exposure are not clear, although humans may be exposed to TBECH via indoor dust and air. In birds and fish there is some evidence of disruption in endocrine and reproductive parameters due to TBECH. In vitro studies indicate that TBECH is an androgen receptor agonist. In this study rats were exposed to 0, 10, 50, 250, 1250 or 5000mg/kg technical TBECH for 28days in diet, corresponding to 0, 0...
December 5, 2016: Toxicology
https://www.readbyqxmd.com/read/27916585/perinatal-exposure-to-glyphosate-based-herbicide-alters-the-thyrotrophic-axis-and-causes-thyroid-hormone-homeostasis-imbalance-in-male-rats
#19
Janaina Sena de Souza, Marina Malta Letro Kizys, Rodrigo Rodrigues da Conceição, Gabriel Glebocki, Renata Marino Romano, Tania Maria Ortiga-Carvalho, Gisele Giannocco, Ismael Dale Cotrim Guerreiro da Silva, Magnus Regios Dias da Silva, Marco Aurélio Romano, Maria Izabel Chiamolera
Glyphosate-based herbicides (GBHs) are widely used in agriculture. Recently, several animal and epidemiological studies have been conducted to understand the effects of these chemicals as an endocrine disruptor for the gonadal system. The aim of the present study was to determine whether GBHs could also disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Female pregnant Wistar rats were exposed to a solution containing GBH Roundup(®)Transorb (Monsanto). The animals were divided into three groups (control, 5mg/kg/day or 50mg/kg/day) and exposed from gestation day 18 (GD18) to post-natal day 5 (PND5)...
December 1, 2016: Toxicology
https://www.readbyqxmd.com/read/27915097/effects-of-chronic-lead-exposure-on-bone-mineral-properties-in-femurs-of-growing-rats
#20
Pedro Álvarez-Lloret, Ching Ming Lee, María Inés Conti, Antonela Romina Terrizzi, Santiago González-López, María Pilar Martínez
Lead exposure has been associated with several defective skeletal growth processes and bone mineral alterations. The aim of the present study is to make a more detailed description of the toxic effects of lead intoxication on bone intrinsic material properties as mineral composition, morphology and microstructural characteristics. For this purpose, Wistar rats were exposed (n=12) to 1000ppm lead acetate in drinking water for 90days while control group (n=8) were treated with sodium acetate. Femurs were examined using inductively coupled plasma optical emission spectrometry (ICP-OES), Attenuated Total Reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and micro-Computed Tomography (μCT)...
November 30, 2016: Toxicology
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