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Archives of Toxicology

Mohamed F Abdallah, Marthe De Boevre, Kris Audenaert, Geert Haesaert, Sarah De Saeger
No abstract text is available yet for this article.
April 13, 2018: Archives of Toxicology
Christopher J Borgert, John C Matthews, Stephen P Baker
The European Commission has recently proposed draft criteria for the identification of endocrine disrupting chemicals (EDCs) that pose a significant hazard to humans or the environment. Identifying and characterizing toxic hazards based on the manner by which adverse effects are produced rather than on the nature of those adverse effects departs from traditional practice and requires a proper interpretation of the evidence regarding the chemical's ability to produce physiological effect(s) via a specific mode of action (MoA)...
April 9, 2018: Archives of Toxicology
Dhirendra P Singh, Gagandeep Kaur, Prathyusha Bagam, Rakeysha Pinkston, Sanjay Batra
Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death and disability worldwide by 2030; with cigarette smoking (active or passive) being one of the chief cause of its occurrence. Cigarette smoke exposure has been found to result in excessive inflammation and tissue injury, which might lead to COPD, although the exact pathophysiology of the disease remains elusive. While previous studies have demonstrated the role of membrane-bound Toll-like receptors (TLRs) in cigarette smoke (CS)-induced inflammation, scant information is available about the role of cytosolic NOD-like receptors (NLRs) in regulating CS-mediated inflammatory responses...
April 6, 2018: Archives of Toxicology
Si Chen, Qiangen Wu, Baitang Ning, Matthew Bryant, Lei Guo
Dronedarone is used to treat patients with cardiac arrhythmias and has been reported to be associated with liver injury. Our previous mechanistic work demonstrated that DNA damage-induced apoptosis contributes to the cytotoxicity of dronedarone. In this study, we examined further the underlying mechanisms and found that after a 24-h treatment of HepG2 cells, dronedarone caused cytotoxicity, G1-phase cell cycle arrest, suppression of topoisomerase II, and DNA damage in a concentration-dependent manner. We also investigated the role of cytochrome P450s (CYPs)-mediated metabolism in the dronedarone-induced toxicity using our previously established HepG2 cell lines expressing individually 14 human CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7)...
April 3, 2018: Archives of Toxicology
Gisele Dallapicola Brisson, Bruno de Almeida Lopes, Francianne Gomes Andrade, Filipe Vicente Dos Santos Bueno, Ingrid Sardou-Cezar, Bruno Alves de Aguiar Gonçalves, Eugênia Terra-Granado, Flávio Henrique Paraguassú-Braga, Maria S Pombo-de-Oliveira
Experimental and epidemiological data have shown that acute myeloid leukemia in early-age (i-AML) originates prenatally. The risk association between transplacental exposure to benzene metabolites and i-AML might be influenced by genetic susceptibility. In this study, we investigated the relationship between genetic polymorphisms in CYP2E1, EPHX1, MPO, NQO1, GSTM1 and GSTT1 genes, and i-AML risk. The study included 101 i-AMLs and 416 healthy controls. Genomic DNA from study subjects was purified from bone marrow or peripheral blood aspirates and genotyped for genetic polymorphisms by real-time PCR allelic discrimination, Sanger sequencing and multiplex PCR...
March 31, 2018: Archives of Toxicology
S M Müller, H Finke, F Ebert, J F Kopp, F Schumacher, B Kleuser, K A Francesconi, G Raber, T Schwerdtle
Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents...
March 30, 2018: Archives of Toxicology
Yutaka Kimura, Chizu Fujimura, Yumiko Ito, Toshiya Takahashi, Hitoshi Terui, Setsuya Aiba
We established a luciferase reporter assay system, the Multi-ImmunoTox Assay (MITA), which can evaluate the effects of chemicals on the promoter activities of four cytokines: IL-2, IFN-γ, IL-1β, and IL-8. We previously reported that MITA correctly reflected the change in mRNA of human whole-blood cells treated with dexamethasone, cyclosporine, FK506, or several other immunosuppressive drugs. In this study, we combined MITA with the IL-8 Luc assay to detect skin sensitization chemicals (OECD 442E) (modified MITA: mMITA) and established a data set of 60 chemicals examined by mMITA...
March 29, 2018: Archives of Toxicology
Luigi Barrea, Giovanna Muscogiuri, Carolina Di Somma, Giuseppe Annunziata, Matteo Megna, Andrea Falco, Anna Balato, Annamaria Colao, Silvia Savastano
Despite the wide consumption of coffee, its anti-inflammatory effect on clinical severity of psoriasis is still debatable. The aim of this study was to evaluate the association between the coffee consumption and clinical severity of psoriasis in a sample of patients stratified according to the presence of the metabolic syndrome (MetS) and smoking. This cross-sectional case-control observational study was conducted on 221 treatment-naïve psoriatic patients. Lifestyle habits, anthropometric measures, clinical and biochemical evaluations were obtained...
March 28, 2018: Archives of Toxicology
Ana Santos-Llamas, Maria J Monte, Jose J G Marin, Maria J Perez
The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect relationship between mtDNA status alterations and autophagy has been reported. Both events are common in several liver diseases, including hepatocellular carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA depletion induced by AZT administration in drinking water for 35 days. AZT at a concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased mtDNA levels in rat liver and extrahepatic tissues...
March 28, 2018: Archives of Toxicology
Miriam Pons, Claudia M Reichardt, Dorle Hennig, Abinaya Nathan, Nicole Kiweler, Carol Stocking, Christian Wichmann, Markus Christmann, Falk Butter, Sigrid Reichardt, Günter Schneider, Thorsten Heinzel, Christoph Englert, Jörg Hartkamp, Oliver H Krämer, Nisintha Mahendrarajah
A remaining expression of the transcription factor Wilms tumor 1 (WT1) after cytotoxic chemotherapy indicates remaining leukemic clones in patients. We determined the regulation and relevance of WT1 in leukemic cells exposed to replicative stress and DNA damage. To induce these conditions, we used the clinically relevant chemotherapeutics hydroxyurea and doxorubicin. We additionally treated cells with the pro-apoptotic kinase inhibitor staurosporine. Our data show that these agents promote apoptosis to a variable extent in a panel of 12 leukemic cell lines and that caspases cleave WT1 during apoptosis...
March 27, 2018: Archives of Toxicology
Mei Jing Piao, Mee Jung Ahn, Kyoung Ah Kang, Yea Seong Ryu, Yu Jae Hyun, Kristina Shilnikova, Ao Xuan Zhen, Jin Woo Jeong, Yung Hyun Choi, Hee Kyoung Kang, Young Sang Koh, Jin Won Hyun
The skin is the largest organ of the human body and the one mostly exposed to outdoor contaminants. To evaluate the biological mechanisms underlying skin damage caused by fine particulate matter (PM2.5 ), we analyzed the effects of PM2.5 on cultured human keratinocytes and the skin of experimental animals. PM2.5 was applied to human HaCaT keratinocytes at 50 µg/mL for 24 h and to mouse skin at 100 µg/mL for 7 days. The results indicate that PM2.5 induced oxidative stress by generating reactive oxygen species both in vitro and in vivo, which led to DNA damage, lipid peroxidation, and protein carbonylation...
March 26, 2018: Archives of Toxicology
Cecilie Hurup Munkboel, Michelle L K Baake, Bjarne Styrishave
Obesity is increasing worldwide, and since obesity is associated with dyslipidemia, the consumption of cholesterol-lowering pharmaceuticals has increased. The aim of this study was therefore to study potential endocrine disrupting effects of one of the world's most frequently prescribed drugs, the cholesterol-lowering drug, atorvastatin (ATO) in vitro using the H295R steroidogenesis assay and in vivo using male Sprague-Dawley rats. We analyzed all major steroids in the mammalian steroidogenesis using liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
March 24, 2018: Archives of Toxicology
Mathieu Vinken
No abstract text is available yet for this article.
March 24, 2018: Archives of Toxicology
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0...
March 20, 2018: Archives of Toxicology
Francois Pognan, J Andreas Mahl, Maria Papoutsi, David Ledieu, Marc Raccuglia, Diethilde Theil, Sarah B Voytek, Patrick J Devine, Katie Kubek-Luck, Natalie Claudio, Andre Cordier, Annabelle Heier, Carine Kolly, Andreas Hartmann, Salah-Dine Chibout, Page Bouchard, Christian Trendelenburg
A high incidence of hemangiosarcoma (HSA) was observed in mice treated for 2 years with siponimod, a sphingosine-1-phosphate receptor 1 (S1P1) functional antagonist, while no such tumors were observed in rats under the same treatment conditions. In 3-month rat (90 mg/kg/day) and 9-month mouse (25 and 75 mg/kg/day) in vivo mechanistic studies, vascular endothelial cell (VEC) activation was observed in both species, but VEC proliferation and persistent increases in circulating placental growth factor 2 (PLGF2) were only seen in the mouse...
March 19, 2018: Archives of Toxicology
Violaine Sironval, Laurence Reylandt, Perrine Chaurand, Saloua Ibouraadaten, Mihaly Palmai-Pallag, Yousof Yakoub, Bernard Ucakar, Jérôme Rose, Claude Poleunis, Rita Vanbever, Etienne Marbaix, Dominique Lison, Sybille van den Brule
Rechargeable Li-ion batteries (LIB) are increasingly produced and used worldwide. LIB electrodes are made of micrometric and low solubility particles, consisting of toxicologically relevant elements. The health hazard of these materials is not known. Here, we investigated the respiratory hazard of three leading LIB components (LiFePO4 or LFP, Li4 Ti5 O12 or LTO, and LiCoO2 or LCO) and their mechanisms of action. Particles were characterized physico-chemically and elemental bioaccessibility was documented. Lung inflammation and fibrotic responses, as well as particle persistence and ion bioavailability, were assessed in mice after aspiration of LIB particles (0...
March 17, 2018: Archives of Toxicology
Jeremy Gingrich, Yong Pu, Jennifer Roberts, Rajendiran Karthikraj, Kurunthachalam Kannan, Richard Ehrhardt, Almudena Veiga-Lopez
Exposure to bisphenolic chemicals during pregnancy occurs in > 90% of pregnancies. Bisphenolic compounds can cross the placental barrier reaching fetal circulation. However, the effects of emerging bisphenolic compounds, such as bisphenol S (BPS), on placental function remain untested. The aim was to determine if bisphenol A (BPA) or BPS, at an environmentally relevant dose, impairs placental function. Pregnant sheep were randomly distributed into three treatment groups (n = 7-8/group): control, BPA, and BPS...
March 17, 2018: Archives of Toxicology
Jana Tomc, Katja Kološa, Bojana Žegura, Urška Kamenšek, Barbara Breznik, Tamara Lah Turnšek, Metka Filipič
The problem of the currently used routine genotoxicity tests is relatively low predictivity of in vitro tests for in vivo genotoxicity and carcinogenicity. An important reason is considered to be inadequate expression of xenobiotic-metabolizing enzymes in indicator cell lines. The aim of our study was to generate metabolically active differentiated hepatic progenies (hDHP) from human adipose tissue-derived mesenchymal stem cells (hASC) for genotoxicity testing. hDHP, generated using a three-step hepatic differentiation procedure, expressed hepatic properties such as glycogen storage and albumin secretion...
March 16, 2018: Archives of Toxicology
Fiona Sewell, Nichola Gellatly, Maria Beaumont, Natalie Burden, Richard Currie, Lolke de Haan, Thomas H Hutchinson, Miriam Jacobs, Catherine Mahony, Ian Malcomber, Jyotigna Mehta, Graham Whale, Ian Kimber
The advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise. The purpose of this article is to consider specifically how the future trajectory of AOPs may provide a basis for addressing some of those challenges and opportunities...
March 16, 2018: Archives of Toxicology
Ariane Lenzner, Bärbel Vieth, Andreas Luch
No abstract text is available yet for this article.
March 16, 2018: Archives of Toxicology
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