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Toxicology in Vitro: An International Journal Published in Association with BIBRA

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https://www.readbyqxmd.com/read/29104035/development-of-a-dual-luciferase-activity-and-fluorescamine-protein-assay-adapted-to-a-384-micro-well-plate-format-reducing-variability-in-human-luciferase-transactivation-cell-lines-aimed-at-endocrine-active-substances
#1
Jennifer C Brennan, Donald E Tillitt
There is a need to adapt cell bioassays to 384-well and 1536-well formats instead of the traditional 96-well format as high-throughput screening (HTS) demands increase. However, the sensitivity and performance of the bioassay must be re-verified in these higher micro-well plates, and verification of cell health must also be HT (high-throughput). We have adapted two commonly used human breast luciferase transactivation cell bioassays, the recently re-named estrogen agonist/antagonist screening VM7Luc4E2 cell bioassay (previously designated BG1Luc4E2) and the androgen/glucocorticoid screening MDA-kb2 cell bioassay, to 384-well formats for HTS of endocrine-active substances (EASs)...
November 8, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29117515/metformin-and-epothilone-a-treatment-up-regulate-pro-apoptotic-parp-1-casp-3-and-h2ax-genes-and-decrease-of-akt-kinase-level-to-control-cell-death-of-human-hepatocellular-carcinoma-and-ovary-adenocarcinoma-cells
#2
Aneta Rogalska, Barbara Bukowska, Agnieszka Marczak
High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy. Here, we investigated genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) in combination with respect to apoptosis in HepG2 and SKOV-3 cancer cells. Reactive oxygen species (ROS) was studied using 2',7'-dichlorodihydrofluoresein diacetate, and samples were analyzed for the presence and absence of the N-acetylcysteine (NAC). Expression of genes involved in programmed cell death, oxidative and alkylating DNA damage was measured...
November 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29100959/steroidogenic-disruptive-effects-of-the-serotonin-noradrenaline-reuptake-inhibitors-duloxetine-venlafaxine-and-tramadol-in-the-h295r-cell-assay-and-in-a-recombinant-cyp17-assay
#3
Julie Islin, Cecilie Hurup Munkboel, Bjarne Styrishave
The aim of this study was to determine the steroidogenic endocrine disrupting effect of three widely used serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol, using two in vitro models, the H295R assay and a recombinant CYP17 enzyme assay. Steroid hormones were quantified using LC-MS/MS. Duloxetine showed endocrine disrupting effects at 5-20μM with CYP17 being the main target. Venlafaxine also affected the steroidogenesis, mainly by affecting the CYP17 lyase reaction, although at much higher concentrations i...
October 31, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29111319/micronuclei-formation-in-rainbow-trout-cells-exposed-to-multiple-stressors-morpholine-heat-shock-and-ionizing-radiation
#4
Shayenthiran Sreetharan, Christopher Thome, Kara K Tsang, Christopher M Somers, Richard G Manzon, Douglas R Boreham, Joanna Y Wilson
Discharges from industrial cooling water systems can include low levels of morpholine (a chemical pH regulator and corrosion inhibitor), as well as transiently higher temperature effluent water which present a potential source of environmental impact to aquatic biota. The effects of environmental levels of morpholine or heat shock (HS) treatment alone and in combination with a challenge high-dose of (137)Cs ionizing radiation were studied using the cytokinesis block micronucleus assay in a rainbow trout cell line (RTG-2)...
October 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29107685/toxicity-and-structure-activity-relationship-sar-of-%C3%AE-%C3%AE-dehydroamino-acids-against-human-cancer-cell-lines
#5
Romeu A Videira, Paula B Andrade, Luís S Monteiro, Patrícia Valentão, Paula M T Ferreira, David M Pereira
A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells...
October 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29107684/ethylene-glycol-dimethacrylate-and-diethylene-glycol-dimethacrylate-exhibits-cytotoxic-and-genotoxic-effect-on-human-gingival-fibroblasts-via-induction-of-reactive-oxygen-species
#6
Anna Bielecka-Kowalska, Piotr Czarny, Paulina Wigner, Ewelina Synowiec, Bartosz Kowalski, Marzena Szwed, Renata Krupa, Monika Toma, Malgorzata Drzewiecka, Ireneusz Majsterek, Janusz Szemraj, Tomasz Sliwinski, Michał Kowalski
Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase...
October 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29107018/flubendazole-induces-mitotic-catastrophe-and-apoptosis-in-melanoma-cells
#7
K Čáňová, L Rozkydalová, D Vokurková, E Rudolf
Flubendazole (FLU) is a widely used anthelmintic drug belonging to benzimidazole group. Recently, several studies have been published demonstrating its potential to inhibit growth of various tumor cells including those derived from colorectal cancer, breast cancer or leukemia via several mechanisms. In the present study we have investigated cytotoxic effects of FLU on malignant melanoma using A-375, BOWES and RPMI-7951 cell lines representing diverse melanoma molecular types. In all three cell lines, FLU inhibited cell growth and proliferation and disrupted microtubule structure and function which was accompanied by dramatic changes in cellular morphology...
October 26, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29080800/a-multi-biomarker-analysis-of-the-antioxidant-efficacy-of-parkinson-s-disease-therapy
#8
Monica Colamartino, Guglielmo Duranti, Roberta Ceci, Stefania Sabatini, Antonella Testa, Renata Cozzi
Substantial evidences suggest that reactive oxygen species participate in the normal aging process and in cancer and neurodegenerative age-related diseases. Parkinson's disease (PD), one of the most common oxidative stress-associated pathology in aging people, is treated with a standard pharmacological protocol consisting in a combined therapy l-dopa plus an inhibitor of dopa-decarboxylase, such as carbidopa. The therapy is well validated for the ability to restoring dopaminergic neurotransmission in PD patients, while l-dopa and carbidopa ability in modulating oxidative stress is currently under discussion...
October 26, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29074229/titanium-dioxide-nanoparticles-induce-human-eosinophil-adhesion-onto-endothelial-ea-hy926-cells-via-activation-of-phosphoinositide-3-kinase-akt-cell-signalling-pathway
#9
Maxime Murphy-Marion, Denis Girard
The use of nanoparticles (NPs) for developing new therapeutic strategies in a variety of diseases is gaining increasing attention. However, NPs could possess undesired effects, including pro-inflammatory activities. Despite the fact that several studies reported that NPs may induce or exacerbate eosinophilic inflammation in vivo, information regarding the direct interaction between NPs and eosinophils is lacking. Here, we studied how the most studied nanoparticle (NP), titanium dioxide (TiO2) could alter the capacity of human eosinophils to adhere onto a cellular substratum...
October 23, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29066354/molecular-mechanism-of-action-of-oxazolinoanthracyclines-in-cells-derived-from-human-solid-tumors-part-2
#10
Marta Denel-Bobrowska, Małgorzata Łukawska, Barbara Bukowska, Arkadiusz Gajek, Irena Oszczapowicz, Agnieszka Marczak
BACKGROUND/AIM: Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity. MATERIALS AND METHODS: Experimental model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the concentration of 80nM...
October 21, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29066353/generalized-concentration-addition-accurately-predicts-estrogenic-potentials-of-mixtures-and-environmental-samples-containing-partial-agonists
#11
Markus Brinkmann, Markus Hecker, John P Giesy, Paul D Jones, Hans Toni Ratte, Henner Hollert, Thomas G Preuss
Cell-based bioanalytical tools are considered one alternative to overcome limitations of sensitivities of instrumental, analytical chemistry for monitoring estrogenic chemicals in the environment. Because these tools also reflect non-additive interactions of chemicals in mixtures, their outcomes often deviate from outcomes of chemical analytical approaches that assume additivity, e.g. the concentration addition (CA) model. Often this is because CA is unable to adequately represent effects of partial agonists, i...
October 21, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29054701/intra-and-inter-laboratory-reproducibility-and-predictivity-of-the-hacasens-assay-a-skin-sensitization-test-using-human-keratinocytes-hacat
#12
Hyewon Chung, Hailian Quan, Daun Jung, Gautam Ravi, Ahrang Cho, Mi Jeong Kang, Eunju Kim, Jeong-Hwan Che, Eung-Seok Lee, Tae Cheon Jeong, Yong Heo, Seung Hyeok Seok
Due to considerable constraints in using animals for risk assessment, much effort has been directed at developing non-animal test methods. Developing assays for skin sensitization, the leading cause of contact dermatitis, is particularly important, but there are currently no in vitro skin sensitization tests that completely replace animal tests. HaCaSens, a simple skin sensitization test using non-transformed HaCaT cells, predicts keratinocyte activation by skin sensitizers with 75% sensitivity, 83% specificity and 77% accuracy in a previous study using 22 coded substances...
October 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29054700/rebamipide-suppresses-5-fluorouracil-induced-cell-death-via-the-activation-of-akt-mtor-pathway-and-regulates-the-expression-of-bcl-2-family-proteins
#13
Masanobu Tsubaki, Tomoya Takeda, Ryo-Ta Asano, Tomoyuki Matsuda, Shin-Ichiro Fujimoto, Tatsuki Itoh, Motohiro Imano, Takao Satou, Shozo Nishida
Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells)...
October 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29054699/silymarin-attenuated-paraquat-induced-cytotoxicity-in-macrophage-by-regulating-trx-txnip-complex-inhibiting-nlrp3-inflammasome-activation-and-apoptosis
#14
Zhenning Liu, Mingli Sun, Yu Wang, Lichun Zhang, Hang Zhao, Min Zhao
Oxidative stress and inflammation are involved in paraquat-induced cytotoxicity. Silymarin can exert a potent antioxidative and anti-inflammatory effect in various pathophysiological processes. The aim of this current study is to explore the protective effect and potential mechanism of silymarin in paraquat-induced macrophage injury. Cells were pretreated with different doses of silymarin for 3h before exposure to paraquat. At 24h after exposure to paraquat, the paraquat-induced cytotoxicity to macrophage was measured via the MTT assay and LDH release...
October 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29032072/oxidative-stress-prediction-a-preliminary-approach-using-a-response-surface-based-technique
#15
M Sierra, L Bragg-Gonzalo, J Grasa, M J Muñoz, D González, F J Miana-Mena
A response surface was built to predict the lipid peroxidation level, generated in an iron-ascorbate in vitro model, of any organ, which is correlated with the oxidative stress injury in biological membranes. Oxidative stress studies are numerous, usually performed on laboratory animals. However, ethical concerns require validated methods to reduce the use of laboratory animals. The response surface described here is a validated method to replace animals. Tissue samples of rabbit liver, kidney, heart, skeletal muscle and brain were oxidized with different concentrations of FeCl3 (0...
October 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29031482/toxicologic-transport-properties-of-ncs-382-a-%C3%AE-hydroxybutyrate-ghb-receptor-ligand-in-neuronal-and-epithelial-cells-therapeutic-implications-for-ssadh-deficiency-a-gaba-metabolic-disorder
#16
K R Vogel, G R Ainslie, A McConnell, J-B Roullet, K M Gibson
We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB receptor ligand, NCS-382, using neuronal stem cells derived from mice with a targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde dehydrogenase(SSADH)-deficient mice). These animals represent a phenocopy of the human disorder of GABA metabolism, SSADH deficiency, that metabolically features accumulation of both GABA and the GABA-analog γ-hydroxybutyric acid in conjunction with a nonspecific neurological phenotype...
October 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29030288/in-vitro-characterization-of-zebrafish-danio-rerio-organic-anion-transporters-oat2a-e
#17
Jelena Dragojević, Ivan Mihaljević, Marta Popović, Roko Zaja, Tvrtko Smital
OATS/Oats are transmembrane proteins that transport a variety of drugs, environmental toxins and endogenous metabolites into the cell. Zebrafish (Danio rerio) has seven OAT orthologs: Oat1, Oat2a-e and Oat3. In this study we specifically address Oat2 (Slc22a7) family. Conserved synteny analysis showed localization of zebrafish oat2 genes on two chromosomes, 11 and 17. All five zebrafish Oats were localized by live cell imaging in membranes of transiently transfected HEK293-T cells, and Oat2a, b, d, and e were confirmed using western blot analysis...
October 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29024780/toxicogenomics-of-the-flame-retardant-tris-2-butoxyethyl-phosphate-in-hepg2-cells-using-rna-seq
#18
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Bart Cuypers, Kris Laukens, Ronny Blust, Steven J Husson
Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29024779/kinetic-characterization-of-bile-salt-transport-by-human-ntcp-slc10a1
#19
Márton Jani, Erzsébet Beéry, Teresa Heslop, Beáta Tóth, Bhavana Jagota, Emese Kis, B Kevin Park, Peter Krajcsi, Richard J Weaver
The transport of bile acids facilitated by NTCP is an important factor in establishing bile flow. In this study, we examine the kinetics associated with human NTCP-dependent transport of two quantitatively important bile acids comprising the human bile acid pool, chenodeoxycholic acid and glycine-chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of potential toxicological significance. The study employed human NTCP overexpressing Chinese Hamster Ovary cells and results compared with taurocholate, a prototypical bile salt commonly used in transporter studies...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29024778/direct-comparison-between-in-vivo-and-in-vitro-microsized-particle-phagocytosis-assays-in-drosophila-melanogaster
#20
K Adolfsson, L Abariute, A P Dabkowska, M Schneider, U Häcker, C N Prinz
The effects of micro and nanoparticles on the innate immune system have been widely investigated and a general lack of agreement between in vivo and in vitro assays has been observed. In order to determine the origin of these discrepancies, there is a need for comparing the results of in vivo and in vitro phagocytosis assays obtained using the same particles and same immune cells. Here, we establish an in vivo polystyrene microsized particle phagocytosis assay in Drosophila melanogaster and compare it with an in vitro assay consisting of exposing the same immune cells in culture to the same particles...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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