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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/28108177/discriminating-between-adaptive-and-carcinogenic-liver-hypertrophy-in-rat-studies-using-logistic-ridge-regression-analysis-of-toxicogenomic-data-the-mode-of-action-and-predictive-models
#1
Shujie Liu, Taisuke Kawamoto, Osamu Morita, Kouichi Yoshinari, Hiroshi Honda
Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds...
January 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28095306/the-role-of-pten-in-regulation-of-hepatic-macrophages-activation-and-function-in-progression-and-reversal-of-liver-fibrosis
#2
Yahui Cheng, Yuanyao Tian, Jialu Xia, Xiaoqin Wu, Yang Yang, Xiaofeng Li, Cheng Huang, Xiaoming Meng, Taotao Ma, Jun Li
Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl4-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl4-induced mice but increased to a near-normal level in reversed mice...
January 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28089945/zearalenone-exposure-impairs-ovarian-primordial-follicle-formation-via-down-regulation-of-lhx8-expression-in-vitro
#3
Guo-Liang Zhang, Xiao-Feng Sun, Yan-Zhong Feng, Bo Li, Ya-Peng Li, Fan Yang, Charles Martin Nyachoti, Wei Shen, Shi-Duo Sun, Lan Li
Zearalenone (ZEA) is an estrogenic mycotoxin mainly produced as a secondary metabolite by numerous species of Fusarium. Previous work showed that ZEA had a negative impact on domestic animals with regard to reproduction. The adverse effects and the mechanisms of ZEA on mammalian ovarian folliculogenesis remain largely unknown, particularly its effect on primordial follicle formation. Thus, we investigated the biological effects of ZEA exposure on murine ovarian germ cell cyst breakdown and primordial follicle assembly...
January 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28087322/cutaneous-exposure-to-vesicant-phosgene-oxime-acute-effects-on-the-skin-and-systemic-toxicity
#4
Neera Tewari-Singh, Dinesh G Goswami, Rama Kant, Claire R Croutch, Robert P Casillas, David J Orlicky, Rajesh Agarwal
Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model...
January 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28077287/iron-oxide-nanoparticles-modulate-heat-shock-proteins-and-organ-specific-markers-expression-in-mice-male-accessory-organs
#5
Kiruthika Sundarraj, Azhwar Raghunath, Lakshmikanthan Panneerselvam, Ekambaram Perumal
With increased industrial utilization of iron oxide nanoparticles (Fe2O3-NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe2O3-NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe2O3-NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1)...
January 7, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28063877/myeloid-differentiation-protein-2-dependent-mechanisms-in-retinal-ischemia-reperfusion-injury
#6
Luqing Ren, Jianjian Tao, Huaicheng Chen, Yang Bian, Xi Yang, Gaozhi Chen, Xin Zhang, Guang Liang, Wencan Wu, Zongming Song, Yi Wang
Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury...
January 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28041785/a-semi-quantitative-translational-pharmacology-analysis-to-understand-the-relationship-between-in-vitro-ent1-inhibition-and-the-clinical-incidence-of-dyspnoea-and-bronchospasm
#7
Lyn Rosenbrier Ribeiro, R Ian Storer
Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations...
December 29, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28041784/in-vitro-neuroprotective-potential-of-lichen-metabolite-fumarprotocetraric-acid-via-intracellular-redox-modulation
#8
Carlos Fernández-Moriano, Pradeep Kumar Divakar, Ana Crespo, M Pilar Gómez-Serranillos
The lichen-forming fungi Cetraria islandica has been largely used in folk medicines, and it has recently showed promising in vitro antioxidant effects in glial-like cells. Current work aimed at investigating the neuroprotective potential of its major isolated secondary metabolite: the depsidone fumarprotocetraric acid (FUM). H2O2 was used herein to induce oxidative stress (OS)-mediated cytotoxicity in two models of neurons and astrocytes cells (SH-SY5Y and U373-MG cell lines). We found that a pre-treatment with FUM significantly enhanced cell viability compared to H2O2-treated cells, and we selected the optimal concentrations in each model (1 and 25μg/ml, respectively) for assessing its cytoprotective mechanisms...
December 29, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28039000/moving-into-advanced-nanomaterials-toxicity-of-rutile-tio2-nanoparticles-immobilized-in-nanokaolin-nanocomposites-on-hepg2-cell-line
#9
Maria João Bessa, Carla Costa, Julian Reinosa, Cristiana Pereira, Sónia Fraga, José Fernández, Miguel A Bañares, João Paulo Teixeira
Immobilization of nanoparticles on inorganic supports has been recently developed, resulting in the creation of nanocomposites. Concerning titanium dioxide nanoparticles (TiO2 NPs(1)), these have already been developed in conjugation with clays, but so far there are no available toxicological studies on these nanocomposites. The present work intended to evaluate the hepatic toxicity of nanocomposites (C-TiO2(2)), constituted by rutile TiO2 NPs immobilized in nanokaolin (NK(3)) clay, and its individual components...
December 28, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28038999/carbonic-anhydrase-inhibition-boosts-the-antitumor-effects-of-imatinib-mesylate-via-potentiating-the-antiangiogenic-and-antimetastatic-machineries
#10
Amal A Abd-El Fattah, Hebatallah A Darwish, Nevine Fathy, Samia A Shouman
Carbonic anhydrase inhibitors have emerged in the past few years as an interesting candidate for the development of novel unconventional strategies. Despite their effect in tumor regression via inhibition of tumor acidification, their potential role is not yet fully elucidated. Herein, we investigated whether acetazolamide (AZ) could modulate imatinib (IM) anticancer activity, both in breast cancer cells (T47D) and in isolated tumor specimens of Ehrlich ascites carcinoma (EAC). The impact of this combination on angiogenesis was evidenced by decreasing PDGF-A expression and enhancing that of TSP-1...
December 28, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28038998/activation-of-ampk-by-berberine-induces-hepatic-lipid-accumulation-by-upregulation-of-fatty-acid-translocase-cd36-in-mice
#11
You-Jin Choi, Kang-Yo Lee, Seung-Hwan Jung, Hyung Sik Kim, Gayong Shim, Mi-Gyeong Kim, Yu-Kyoung Oh, Seon-Hee Oh, Dae Won Jun, Byung-Hoon Lee
Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation...
December 28, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28025111/relationships-among-dna-hypomethylation-cd-and-pb-exposure-and-risk-of-cigarette-smoking-related-urothelial-carcinoma
#12
Chi-Jung Chung, Chao-Hsiang Chang, Saou-Hsing Liou, Chiu-Shong Liu, Huei-Ju Liu, Li-Ching Hsu, Jhih-Sheng Chen, Hui-Ling Lee
Cigarette smoking and environmental exposure to heavy metals are important global health issues, especially for urothelial carcinoma (UC). However, the effects of cadmium and lead exposure, as well as the levels of DNA hypomethylation, on UC risk are limited. We evaluated the possible exposure sources of Cd and Pb and the relationship among DNA hypomethylation, urinary Cd and Pb levels, and UC risk. We recruited 209 patients with UC and 417 control patients for a hospital-based case-control study between June 2011 and August 2014...
December 24, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28025110/hypomethylation-of-inflammatory-genes-cox2-egr1-and-socs3-and-increased-urinary-8-nitroguanine-in-arsenic-exposed-newborns-and-children
#13
Preeyaphan Phookphan, Panida Navasumrit, Somchamai Waraprasit, Jeerawan Promvijit, Krittinee Chaisatra, Thitirat Ngaotepprutaram, Mathuros Ruchirawat
Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis...
December 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28025109/deet-potentiates-the-development-and-persistence-of-anticholinesterase-dependent-chronic-pain-signs-in-a-rat-model-of-gulf-war-illness-pain
#14
L K Flunker, T J Nutter, R D Johnson, B Y Cooper
Exposure to DEET (N,N-diethyl-meta-toluamide) may have influenced the pattern of symptoms observed in soldiers with GWI (Gulf War Illness; Haley and Kurt, 1997). We examined how the addition of DEET (400mg/kg; 50% topical) to an exposure protocol of permethrin (2.6mg/kg; topical), chlorpyrifos (CP; 120mg/kg), and pyridostigmine bromide (PB;13mg/kg) altered the emergence and pattern of pain signs in an animal model of GWI pain (Nutter et al., 2015). Rats underwent behavioral testing before, during and after a 4week exposure: 1) hindlimb pressure withdrawal threshold; 2) ambulation (movement distance and rate); and 3) resting duration...
December 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28025108/di-2-ethylhexyl-phthalate-could-disrupt-the-insulin-signaling-pathway-in-liver-of-sd-rats-and-l02-cells-via-ppar%C3%AE
#15
Wang Zhang, Xin-Yue Shen, Wen-Wen Zhang, Hao Chen, Wei-Ping Xu, Wei Wei
Di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it has been reported to be an endocrine disrupter and ligand to peroxisome proliferator activated receptor, which could influence the homeostasis of liver metabolic systems and contribute to the development of type-2 diabetes. However, the potential mechanisms are not known yet. This study was designed to solve these problems with male SD rats and normal human hepatocyte line, L02 cells, exposed to DEHP for toxicological experiments...
December 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28025107/apigenin-potentiates-the-antitumor-activity-of-5-fu-on-solid-ehrlich-carcinoma-crosstalk-between-apoptotic-and-jnk-mediated-autophagic-cell-death-platforms
#16
Hanaa H Gaballah, Rasha A Gaber, Darin A Mohamed
BACKGROUND: Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention. AIM: This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC). METHODS: Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC+5-FU, SEC+apigenin, SEC+ 5-FU+apigenin...
December 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28017615/pharmacological-activation-of-aldehyde-dehydrogenase-2-promotes-osteoblast-differentiation-via-bone-morphogenetic-protein-2-and-induces-bone-anabolic-effect
#17
Monika Mittal, Subhashis Pal, Shyamsundar Pal China, Konica Porwal, Kapil Dev, Richa Shrivastava, Kanumuri Siva Rama Raju, Mamunur Rashid, Arun Kumar Trivedi, Sabyasachi Sanyal, Muhammad Wahajuddin, Smrati Bhaduria, Rakesh Maurya, Naibedya Chattopadhyay
Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2)...
December 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28007550/gemcitabine-selective-cytotoxicity-induction-of-inflammation-and-effects-on-urothelial-function
#18
Stefanie E Farr, Russ Chess-Williams, Catherine M McDermott
Intravesical gemcitabine has recently been introduced for the treatment of superficial bladder cancer and has a favourable efficacy and toxicity profile in comparison to mitomycin c (MMC), the most commonly used chemotherapeutic agent. The aim of this study was to assess the cytotoxic potency of gemcitabine in comparison to MMC in urothelial cell lines derived from non-malignant (UROtsa) and malignant (RT4 and T24) tissues to assess selectivity. Cells were treated with gemcitabine or mitomycin C at concentrations up to the clinical doses for 1 or 2h respectively (clinical duration)...
December 19, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27989784/emodin-suppresses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-alveolar-epithelial-cells-through-notch-signaling-pathway
#19
Rundi Gao, Ruilin Chen, Yu Cao, Yuan Wang, Kang Song, Ya Zhang, Junchao Yang
Pulmonary fibrosis is characterized by the destruction of lung tissue architecture and the formation of fibrous foci, currently has no satisfactory treatment. Emodin is a component of Chinese herb that has been reported to be medicament on pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis has not been established yet. In the present study, we investigated the hypothesis that Emodin plays an inhibitory role in TGF-β1 induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cell, and Emodin exerts its effect through the Notch signaling pathway...
December 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27986624/ilexgenin-a-exerts-anti-inflammation-and-anti-angiogenesis-effects-through-inhibition-of-stat3-and-pi3k-pathways-and-exhibits-synergistic-effects-with-sorafenib-on-hepatoma-growth
#20
Hao Yang, Juan Wang, Jin-Hong Fan, Ya-Qi Zhang, Jun-Xian Zhao, Xiao-Jun Dai, Qi Liu, Yan-Jun Shen, Chang Liu, Wei-Dong Sun, Yun Sun
Recently, we reported that Ilexgenin A exhibits anti-cancer activities and induces cell arrest. Here, we investigated the effect of Ilexgenin A on the inflammation, angiogenesis and tumor growth of hepatocellular carcinoma (HCC). Our current study revealed that Ilexgenin A significantly inhibited the inflammatory cytokines TNF-α and IL-6 levels and downregulated pro-angiogenic factor VEGF production and transcription in HepG2 cells. The underlying mechanism for Ilexgenin A effects appears to be through inhibiting STAT3 and PI3K pathways...
December 14, 2016: Toxicology and Applied Pharmacology
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