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Journal of Applied Toxicology: JAT

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https://www.readbyqxmd.com/read/29148590/effects-of-bergenin-on-methylglyoxal-induced-damage-in-osteoblastic-mc3t3-e1-cells
#1
Kyung Hee Lee, Eun Mi Choi
Bergenin is the main chemical constituent of plants in the genus Bergenia, which are used in traditional medicines. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is the major precursor for forming advanced glycation end products (AGEs). Pretreating MC3T3-E1 cells with bergenin prevented MG-induced protein adduct formation. Bergenin inhibited the MG-induced soluble receptor for AGE (sRAGE), interleukin, reactive oxygen species and mitochondrial superoxide production. Additionally bergenin increased glyoxalase I activity, glutathione, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 levels in the presence of MG...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29148585/arsenite-downregulates-h3k4-trimethylation-and-h3k9-dimethylation-during-transformation-of-human-bronchial-epithelial-cells
#2
Wei Tu, Yin Liu, Chengfeng Xie, Xue Zhou
Arsenic is an established human carcinogen but with weak mutagenic activity. The mechanisms of arsenic-induced carcinogenesis are not well understood. In the present study, we investigated the role of histone methylation in transformation of human bronchial epithelial (BEAS-2B) cells. After 16 weeks' exposure, cells were transformed by 0.1, 0.5 and 1 μm arsenite. Global trimethylated H3K4 (H3K4me3) was decreased by 0.1 μm arsenite at 12 weeks, and 0.5 and 1 μm arsenite at 8, 12 and 16 weeks, which could be attributed to reduced histone methyltransferase activities, increased histone demethylase (HDM) activities as well as increased protein levels of H3K4 demethylase KDM5A...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29148584/metabolic-effects-of-p-p-dde-on-atlantic-salmon-hepatocytes
#3
Pål A Olsvik, Liv Søfteland
Decades after being banned in many countries, DDT and its metabolites are still considered major environmental hazards. The p,p'-DDE isomer, the DDT metabolite found in highest concentration in aquaculture feeds, is an endocrine disruptor with demonstrated ability to induce epigenetic effects. This study aimed at examining the impact of p,p'-DDE on Atlantic salmon. Primary hepatocytes were exposed to four concentrations of p,p'-DDE (0.1, 1, 10, 100 μm) for 48 hours, and endpoints included cytotoxicity, global DNA methylation, targeted transcription and metabolomics profiling (100 μm)...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143974/%C3%AE-h2ax-formation-in-the-urinary-bladder-of-rats-treated-with-two-norharman-derivatives-obtained-from-o-toluidine-and-aniline
#4
T Toyoda, Y Totsuka, K Matsushita, T Morikawa, N Miyoshi, K Wakabayashi, K Ogawa
Aminomethylphenylnorharman (AMPNH) and aminophenylnorharman (APNH) are mutagenic norharman derivatives obtained from o-toluidine and aniline, respectively. APNH is carcinogenic to the urinary bladder of rats and present in urine samples of healthy volunteers, indicating that norharman derivatives may be associated with cancer development in the urinary bladder of humans. To evaluate the possible role of AMPNH and APNH in bladder carcinogenesis, we examined the formation of γ-H2AX, a DNA damage response marker, in the urinary bladder of rats...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143967/thirteen-week-toxicity-study-of-dietary-l-tryptophan-in-rats-with-a-recovery-period-of-5%C3%A2-weeks
#5
Yusuke Shibui, Hideki Matsumoto, Yoko Masuzawa, Takumi Ohishi, Tsutomu Fukuwatari, Katsumi Shibata, Ryosei Sakai
Although l-tryptophan is nutritionally important and widely used in medical applications, toxicity data for its oral administration are limited. The purpose of this study was to evaluate the potential toxicity of an experimental diet containing added l-tryptophan at doses of 0 (basal diet), 1.25%, 2.5% and 5.0% when administered to Sprague-Dawley rats for 13 weeks. There were no toxicological changes in clinical signs, ophthalmology, urinalysis, hematology, necropsy, organ weight and histopathology between control rats and those fed additional l-tryptophan...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143966/drug-interaction-at-herg-channel-in-vitro-assessment-of-the-electrophysiological-consequences-of-drug-combinations-and-comparison-against-theoretical-models
#6
Barbara Wiśniowska, Bartosz Lisowski, Magdalena Kulig, Sebastian Polak
Drugs carry a proarrhythmic risk, which gets even greater when they are used in combination. In vitro assessment of the proarrhythmic potential of drugs is limited to one compound and thus neglects the potential of drug-drug interactions, including those involving active metabolites. Here we present the results of an in vitro study of potential drug-drug interactions at the level of the hERG channel for the combination of up to three compounds: loratadine, desloratadine and ketoconazole. Experiments were performed at room temperature on an automated patch-clamp device CytoPatch 2, with the use of heterogeneously, stably transfected HEK cells...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143351/apoptotic-and-antiproliferative-properties-of-3%C3%AE-hydroxy-%C3%AE-5-steroidal-congeners-from-a-partially-purified-column-fraction-of-dendronephthya-gigantea-against-hl-60-and-mcf-7-cancer-cells
#7
I P Shanura Fernando, K K Asanka Sanjeewa, Hyun-Soo Kim, Lei Wang, Won Woo Lee, You-Jin Jeon
Organisms belonging to the genus Dendronephthya are among a group of marine invertebrates that produce a variety of terpenoids with biofunctional properties. Many of these terpenoids have been proven effective as anticancer drugs. Here, we report the antiproliferative effect of 3β-hydroxy-Δ5-steroidal congeners against the proliferation of HL-60 human leukemia cells and MCF-7 human breast cancer cells. The sterol-rich fraction (DGEHF2-1) inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 13...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143341/a-toxicogenomics-approach-to-screen-chlorinated-flame-retardants-tris-2-chloroethyl-phosphate-and-tris-2-chloroisopropyl-phosphate-for-potential-health-effects
#8
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Ronny Blust, Steven J Husson
Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29134676/a-safety-and-immunogenicity-study-of-a-novel-subunit-plague-vaccine-in-cynomolgus-macaques
#9
Li Liu, Dong Wei, Zhe Qu, Li Sun, Yufa Miao, Yanwei Yang, Jinbiao Lu, Weixin Du, Bingxiang Wang, Bo Li
Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live-attenuated vaccines call for the development of new vaccines. In this study, we evaluated the immunogenicity and safety of a novel subunit plague vaccine, comprising native F1 antigen and recombinant V antigen. The cynomolgus macaques in low- and high-dose vaccine groups were vaccinated at weeks 0, 2, 4 and 6, at dose levels of 15 μg F1 + 15 μg rV and 30 μg F1 + 30 μg rV respectively...
November 14, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29105116/a-mitochondrial-targeting-tetrapeptide-bendavia-protects-lateral-line-hair-cells-from-gentamicin-exposure
#10
Xiao Kuang, Yanhui Sun, Zhenjie Wang, Shuang Zhou, Hongzhuo Liu
The hearing loss induced by aminoglycosides is caused by the permanent loss of mechanosensory hair cells of the inner ear. The aim of the present study is therefore to evaluate the protective effect of Bendavia, a novel antioxidant, on gentamicin-induced hair cell damage in zebrafish lateral lines. The results demonstrated the pretreatment of Bendavia exhibited dose-dependent protection against gentamicin in both acute and chronic exposure. We found that Bendavia at 150 μm conferred optimal protection from either acute or chronic exposure with ototoxin...
November 3, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29094763/transcriptional-profiling-reveals-gene-expression-changes-associated-with-inflammation-and-cell-proliferation-following-short-term-inhalation-exposure-to-copper-oxide-nanoparticles
#11
Pedro M Costa, Ilse Gosens, Andrew Williams, Lucian Farcal, Daniele Pantano, David M Brown, Vicki Stone, Flemming R Cassee, Sabina Halappanavar, Bengt Fadeel
Our recent studies revealed a dose-dependent proinflammatory response to copper oxide nanoparticles (CuO NPs) in rats following short-term inhalation exposure for five consecutive days. Here transcriptomics approaches were applied using the same model to assess global gene expression in lung tissues obtained 1 day post-exposure and after a recovery period of 22 days from rats exposed to clean air or 6 hour equivalent doses of 3.3 mg m(-3) (low dose) and 13.2 mg m(-3) (high dose). Microarray analyses yielded about 1000 differentially expressed genes in the high-dose group and 200 in low-dose compared to the clean air control group, and less than 20 after the recovery period...
November 2, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29094436/low-level-perfluorooctanoic-acid-enhances-3%C3%A2-t3-l1-preadipocyte-differentiation-via-altering-peroxisome-proliferator-activated-receptor-gamma-expression-and-its-promoter-dna-methylation
#12
Yue Ma, Jie Yang, Yanjian Wan, Yang Peng, Shuai Ding, Yuanyuan Li, Bing Xu, Xi Chen, Wei Xia, Yuebin Ke, Shunqing Xu
Recent studies suggest that perfluorooctanoic acid (PFOA) can play a role in the development of obesity; however, the associated mechanisms are poorly understood. We investigated how PFOA exposure affected the differentiation of 3 T3-L1 preadipocytes and the associated transcriptional and epigenetic mechanisms. Cells treated with different doses of PFOA (ranging from 0.01 to 100 μg ml(-1) ) were assessed for proliferation, differentiation and triglyceride accumulation. The gene expression levels of peroxisome proliferator activated receptor gamma (PPARγ) and its target genes were measured...
November 2, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29072336/mechanisms-of-toxicity-associated-with-six-tyrosine-kinase-inhibitors-in-human-hepatocyte-cell-lines
#13
Cécile Mingard, Franziska Paech, Jamal Bouitbir, Stephan Krähenbühl
Tyrosine kinase inhibitors have revolutionized the treatment of certain cancers. They are usually well tolerated, but can cause adverse reactions including liver injury. Currently, mechanisms of hepatotoxicity associated with tyrosine kinase inhibitors are only partially clarified. We therefore aimed at investigating the toxicity of regorafenib, sorafenib, ponatinib, crizotinib, dasatinib and pazopanib on HepG2 and partially on HepaRG cells. Regorafenib and sorafenib strongly inhibited oxidative metabolism (measured by the Seahorse-XF24 analyzer) and glycolysis, decreased the mitochondrial membrane potential and induced apoptosis and/or necrosis of HepG2 cells at concentrations similar to steady-state plasma concentrations in humans...
October 26, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29064106/integration-of-mechanistic-and-pharmacokinetic-information-to-derive-oral-reference-dose-and-margin-of-exposure-values-for-hexavalent-chromium
#14
Chad M Thompson, Christopher R Kirman, Sean M Hays, Mina Suh, Seneca E Harvey, Deborah M Proctor, Julia E Rager, Laurie C Haws, Mark A Harris
The current US Environmental Protection Agency (EPA) reference dose (RfD) for oral exposure to chromium, 0.003 mg kg(-1)  day(-1) , is based on a no-observable-adverse-effect-level from a 1958 bioassay of rats exposed to ≤25 ppm hexavalent chromium [Cr(VI)] in drinking water. EPA characterizes the confidence in this RfD as "low." A more recent cancer bioassay indicates that Cr(VI) in drinking water is carcinogenic to mice at ≥30 ppm. To assess whether the existing RfD is health protective, neoplastic and non-neoplastic lesions from the 2 year cancer bioassay were modeled in a three-step process...
October 24, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29047155/maduramicin-induces-apoptosis-and-necrosis-and-blocks-autophagic-flux-in-myocardial-h9c2-cells
#15
Xin Chen, Long Chen, Shanxiang Jiang, Shile Huang
Maduramicin, a polyether ionophore antibiotic, is widely used as an anticoccidial agent in the poultry industry. It has been reported that maduramicin may cause heart and skeletal muscle cell damage, resulting in heart failure, skeletal muscle degeneration and even death in animals and humans, if improperly used. However, the molecular mechanism behind its capability to cause death of cardiac cells is not known. Here, we show that maduramicin induced apoptosis and necrosis in rat myocardial cells (H9c2). Maduramicin did not apparently upregulate the expression of pro-apoptotic proteins (e...
October 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29044621/protective-roles-of-hepatic-gamma-aminobutyric-acid-signaling-in-acute-ethanol-exposure-induced-liver-injury
#16
Shuanglian Wang, Shaofeng Sui, Zhiyan Liu, Cheng Peng, Jia Liu, Dan Luo, Xinhuan Fan, Chuanyong Liu, Wei-Yang Lu
Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA) signaling system that protects the liver from toxic injury. The present study was designed to investigate the role of the hepatic GABA signaling system in the process of acute ethanol exposure-induced liver injury. Our results showed that the expression of GABA synthesizing enzyme glutamic acid decarboxylase and type A GABA receptor (GABAA R) subunits was upregulated in ethanol-treated mice compared with saline-treated controls...
October 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29027214/development-of-an-alternative-zebrafish-model-for-drug-induced-intestinal-toxicity
#17
Bokyeong Ryu, C-Yoon Kim, Hanseul Oh, Ukjin Kim, Jin Kim, Cho-Rok Jung, Byoung-Hee Lee, Seungki Lee, Seo-Na Chang, Ji Min Lee, Hyung-Min Chung, Jae-Hak Park
An evaluation of intestinal toxicity is important because the mucosal lining of the gastrointestinal tract is the first barrier for oral xenobiotics. Until now, a rat model has been recommended as the standard intestinal toxicity model and the Caco-2 cell line, originated from a human colon adenocarcinoma, has been used as an alternative to this model, but there are limitations regarding cost-effectiveness and the need for mimicry of the human system. In this study, we investigated whether zebrafish could be a valid alternative to rats and Caco-2 cells as an intestinal toxicity model...
October 13, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29027213/protective-effect-of-metoclopramide-against-organophosphate-induced-apoptosis-in-the-murine-skin-fibroblast-l929
#18
Basem M Jaber, Georg A Petroianu, Syed A Rizvi, Anwar Borai, Nada A Saleh, Sharif M Hala, Ayman M Saleh
This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm) or 1.0 μm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ)...
October 13, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29023806/the-percutaneous-toxicokinetics-of-vx-in-a-damaged-skin-porcine-model-and-the-evaluation-of-woundstat%C3%A2-as-a-topical-decontaminant
#19
Helen Lydon, Charlotte Hall, Hazem Matar, Christopher Dalton, J Kevin Chipman, John S Graham, Robert P Chilcott
This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for the decontamination of superficial, nerve agent-contaminated wounds. Anaesthetized animals were randomly assigned to either control (n = 7), no decontamination (n = 12) or WoundStat™ (n = 12) treatment groups. Pigs were exposed to a 5× LD50 dose of neat, radiolabelled S-[2-(diisopropylamino)ethyl]-O-ethyl methyl-phosphonothioate (VX; or equivalent volume of sterile saline for the control group) via an area of superficially damaged skin on the ear...
October 10, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28990245/effects-of-exposure-to-six-chemical-ultraviolet-filters-commonly-used-in-personal-care-products-on-motility-of-mcf-7-and-mda-mb-231-human-breast-cancer-cells-in-vitro
#20
Maha Alamer, Philippa D Darbre
Benzophenone (BP)-1, BP-2, BP-3, octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor and homosalate are added to personal care products to absorb ultraviolet light. Their presence in human milk and their oestrogenic activity suggests a potential to influence breast cancer development. As metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of these compounds on migration and invasion of human breast cancer cell lines. Increased motility of oestrogen-responsive MCF-7 human breast cancer cells was observed after long-term exposure (>20 weeks) to each of the six compounds at ≥10(-7)  m concentrations using three independent assay systems (scratch assay, live cell imaging, xCELLigence technology) and increased invasive activity was observed through matrigel using the xCELLigence system...
October 9, 2017: Journal of Applied Toxicology: JAT
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