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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/28438631/in-vivo-inhibitory-activity-of-andrographolide-derivative-adn-9-against-liver-cancer-and-its-mechanisms-involved-in-inhibition-of-tumor-angiogenesis
#1
Wei Yang, Jin Zhao, Yake Wang, Haiwei Xu, Zhenwei Wu, Yangyang Hu, Kunkun Jiang, Pengpeng Shen, Cuiyun Ma, Zhenzhen Guan, Yan Zhang, Jiahui Ma, Ning Shang, Guangming Yan, Zhenji Wang, Guifu Dai
It is well known that liver cancer is a highly aggressive malignancy with poor prognosis. Andrographolide (AD), a major bioactive component of Andrographis paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis of AD derivatives with better cytotoxicity to cancer cells has attracted considerable attentions. In the present study, we evaluated the in vivo inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft model and a subcutaneous xenograft model, and we further studied the anti-angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro...
April 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28438630/identification-of-anti-viral-activity-of-the-cardenolides-na-k-atpase-inhibitors-against-porcine-transmissible-gastroenteritis-virus
#2
Cheng-Wei Yang, Hsin-Yu Chang, Hsing-Yu Hsu, Yue-Zhi Lee, Hsun-Shuo Chang, Ih-Sheng Chen, Shiow-Ju Lee
A series of naturally occurring cardenolides that exhibit potent anti-transmissible gastroenteritis virus (TGEV) activity in swine testicular (ST) cells has been identified. In an immunofluorescence assay, these cardenolides were found to diminish the expressions of TGEV nucleocapsid and spike protein, which was used as an indication for viral replication; block TGEV infection induced apoptosis and cytopathic effects; and impart the same trend of inhibitory activity against Na(+)/K(+)-ATPase as for anti-TGEV activity...
April 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28434951/role-of-crf1-receptor-in-post-incisional-plasma-extravasation-and-nociceptive-responses-in-mice
#3
Asunción Romero, Juan-Antonio García-Carmona, María-Luisa Laorden, Margarita M Puig
The corticotropin-releasing factor (CRF) is involved in a number of physiological functions including pain perception. The purpose of this study was to evaluate the role of CRF1 receptor in the long-lasting post-surgical changes in somatic nociceptive thresholds and in local inflammatory responses, using genetically engineered mice lacking functional CRF1 receptor. Animals underwent a plantar incision under anaesthesia with remifentanil (80μg/kg s.c.) and sevoflurane. Mechanical thresholds (von Frey) and plasma extravasation (Evan's blue) were evaluated at different time points...
April 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28433709/pulmonary-pathobiology-induced-by-zinc-oxide-nanoparticles-in-mice-a-24-hour-and-28-day-follow-up-study
#4
Hsiao-Chi Chuang, Kai-Jen Chuang, Jen-Kun Chen, His-En Hua, Yen-Ling Shen, Wei-Neng Liao, Chii-Hong Lee, Chih-Hong Pan, Kuan-Yuan Chen, Kang-Yun Lee, Ta-Chih Hsiao, Tsun-Jen Cheng
Inhaled zinc oxide nanoparticles (ZnONPs) have high deposition rates in the alveolar region of the lungs; however, the adverse health effects of ZnONPs on the respiratory system are unclear. Herein, pathobiological responses of the respiratory system of mice that received intratracheal administration of ZnONPs were investigated by a combination of molecular and imaging (SPECT and CT) approaches. Also, normal BEAS-2B and adenocarcinoma A549 cells were used to confirm the results in mice. First, female BALB/c mice were administrated a series of doses of 20-nm ZnONPs and were compared to the phosphate-buffered saline control for 24-h and 28-day follow-up observations...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#5
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28433707/genetic-susceptibility-to-toxicologic-lung-responses-among-inbred-mouse-strains-following-exposure-to-carbon-nanotubes-and-profiling-of-underlying-gene-networks
#6
Evan A Frank, Vinicius S Carreira, Kumar Shanmukhappa, Mario Medvedovic, Daniel R Prows, Jagjit S Yadav
The risk of human exposure to fiber nanoparticles has risen in recent years due to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs are present as airborne particulates in occupational settings and their hazard potential has been demonstrated in experimental lung exposure studies using inbred mouse strains. However, it is not known whether different inbred strains differ in lung responses to CNTs by virtue of their genetics. In this work, common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL) samples were evaluated over 28days with the objective of evaluating sensitivity/resistance among strains...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28416457/mono-2-ethylhexyl-phthalate-inhibits-human-extravillous-trophoblast-invasion-via-the-ppar%C3%AE-pathway
#7
Fumei Gao, Wenxin Hu, Yu Li, Huan Shen, Jianying Hu
Concerns over the adverse reproductive outcomes in human have been raised, more evidence including the underlying mechanism are required. Since extravillous trophoblast (EVT) invasion is an important physiological step during early development, the effects of mono-2-ethylhexyl phthalate (MEHP), the bioactive metabolite of DEHP, on EVT invasion were investigated using Matrigel-coated transwell chambers and cell line HTR-8/SVneo. In the transwell-based invasive assay, MEHP exposure inhibited EVT invasion as judged by decreased invasion index...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28416456/licoricidin-inhibits-the-growth-of-sw480-human-colorectal-adenocarcinoma-cells-in-vitro-and-in-vivo-by-inducing-cycle-arrest-apoptosis-and-autophagy
#8
Shuai Ji, Shunan Tang, Kai Li, Ziwei Li, Wenfei Liang, Xue Qiao, Qi Wang, Siwang Yu, Min Ye
Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC50 value of 7.2μM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28416455/protection-from-cr-vi-induced-malignant-cell-transformation-and-tumorigenesis-of-cr-vi-transformed-cells-by-luteolin-through-nrf2-signaling
#9
Young-Ok Son, Poyil Pratheeshkumar, Yuting Wang, Donghern Kim, Zhuo Zhang, Xianglin Shi
Cr(VI) is a well known environmental carcinogen, but its mechanism of action and the measures required to mitigate its effects remain to be investigated. Our previous studies showed that exposure of human bronchial epithelial (BEAS-2B) cells to Cr(VI) caused malignant transformation, that these transformed cells progressed through tumorigenesis, and that luteolin, a natural compound, inhibited both of these processes. The present study investigates the underlying mechanisms by which luteolin protects cells against Cr(VI)-induced transformation and tumorigenesis...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28414027/arsenic-activates-the-expression-of-3%C3%AE-hsd-in-mouse-leydig-cells-through-repression-of-histone-h3k9-methylation
#10
Ambreen Alamdar, Guochen Xi, Qingyu Huang, Meiping Tian, Syed Ali Musstjab Akber Shah Eqani, Heqing Shen
Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated...
April 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28414026/targeting-oct2-and-p53-formononetin-prevents-cisplatin-induced-acute-kidney-injury
#11
Di Huang, Chuangyuan Wang, Yingjie Duan, Qiang Meng, Zhihao Liu, Xiaokui Huo, Huijun Sun, Xiaodong Ma, Kexin Liu
Nephrotoxicity is one of major side effects of cisplatin in chemotherapy. Therefore, there is an urgent medical need to develop drugs that may protect kidney from toxicity. In previous study, we found that it showed the protective effects of formononetin against apoptosis by upregulating Nrf2. In this study, we investigated the renoprotective effect of formononetin against cisplatin-induced AKI and tried to elucidate the possible mechanisms. The amelioration of renal function, histopathological changes, and apoptosis in tubular cells was observed after formononetin treatment...
April 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28412310/increased-seizure-susceptibility-and-other-toxicity-symptoms-following-acute-sulforaphane-treatment-in-mice
#12
Katarzyna Socała, Dorota Nieoczym, Edyta Kowalczuk-Vasilev, Elżbieta Wyska, Piotr Wlaź
Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice...
April 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28412309/the-scaffold-protein-rack1-is-a-target-of-endocrine-disrupting-chemicals-edcs-with-important-implication-in-immunity
#13
Erica Buoso, Marilisa Galasso, Melania Ronfani, Angela Papale, Valentina Galbiati, Ivano Eberini, Marina Marinovich, Marco Racchi, Emanuela Corsini
We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p'DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p'DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28412308/genistein-prevention-of-hyperglycemia-and-improvement-of-glucose-tolerance-in-adult-non-obese-diabetic-mice-are-associated-with-alterations-of-gut-microbiome-and-immune-homeostasis
#14
Guannan Huang, Joella Xu, Daniel E Lefever, Travis C Glenn, Tamas Nagy, Tai L Guo
Although studies have linked soy phytoestrogen 4,7,4-trihydroxyisoflavone genistein (GEN) to reduced type 1 diabetes (T1D) risk, the mechanism of dietary GEN on T1D remains unknown. In our studies, adult non-obese diabetic (NOD) mouse model was employed to investigate the effects of GEN exposure on blood glucose level (BGL), glucose tolerance, gut microbiome, and immune responses. Adult male and female NOD mice were fed with either soy-based or casein-based diet, and received GEN at 20mg/kg body weight by gavage daily...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28412307/the-9th-conference-on-metal-toxicity-and-carcinogenesis-the-conference-overview
#15
James T F Wise, Lei Wang, Zhuo Zhang, Xianglin Shi
Heavy metals, such as arsenic, chromium, cadmium, nickel, mercury, and uranium are known to cause many human diseases and health complications after occupational or environmental exposure. Consequently, metals are environmental health concerns. This manuscript is an overview of the 9th Conference on Metal Toxicity and Carcinogenesis held in October 2016 in Lexington, Kentucky. Since 2000, this biennial meeting brings together experts in the field to discuss current and prospective research in an effort to advance research pertaining to metal toxicity and carcinogenesis...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28411035/altered-ion-transport-in-normal-human-bronchial-epithelial-cells-following-exposure-to-chemically-distinct-metal-welding-fume-particles
#16
Jeffrey S Fedan, Janet A Thompson, Terence G Meighan, Patti C Zeidler-Erdely, James M Antonini
Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28411036/prolonged-particulate-chromate-exposure-does-not-inhibit-homologous-recombination-repair-in-north-atlantic-right-whale-eubalaena-glacialis-lung-cells
#17
Cynthia L Browning, Catherine F Wise, John Pierce Wise
Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability...
April 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#18
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28400118/pre-clinical-therapeutic-development-of-a-series-of-metalloporphyrins-for-parkinson-s-disease
#19
Li-Ping Liang, Jie Huang, Ruth Fulton, Jennifer N Pearson-Smith, Brian J Day, Manisha Patel
Reactive oxygen species are a well-defined therapeutic target for Parkinson's disease (PD) and pharmacological agents that catalytically scavenge reactive species are promising neuroprotective strategies for treatment. Metalloporphyrins are synthetic catalytic antioxidants that mimic the body's own antioxidant enzymes i.e. superoxide dismutases and catalase. The goal of this study was to determine if newly designed metalloporphyrins have enhanced pharmacodynamics including oral bioavailability, longer plasma elimination half-lives, penetrate the blood brain barrier, and show promise for PD treatment...
April 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28396216/assessment-of-the-potential-activity-of-major-dietary-compounds-as-selective-estrogen-receptor-modulators-in-two-distinct-cell-models-for-proliferation-and-differentiation
#20
Sylvain Lecomte, Marie Lelong, Gaëlle Bourgine, Theo Efstathiou, Christian Saligaut, Farzad Pakdel
Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity...
April 7, 2017: Toxicology and Applied Pharmacology
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