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    6862 results match your criteria Archives of Toxicology[Journal]

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    A structure-activity relationship linking non-planar PCBs to functional deficits of neural crest cells: new roles for connexins.
    Arch Toxicol 2017 Nov 21. Epub 2017 Nov 21.
    In vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.
    Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the 'migration-inhibition of NCC (cMINC)' assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate. Read More

    Nuclear transport of the human aryl hydrocarbon receptor and subsequent gene induction relies on its residue histidine 291.
    Arch Toxicol 2017 Nov 21. Epub 2017 Nov 21.
    Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.
    The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor involved in the metabolism of physiological substances and xenobiotics, representing an interesting target in both toxicology and pharmacology. In this study, we investigated the ligand-dependent conjunction of nuclear import of the human AHR in living cells and target gene induction. Our findings strengthen the theory that the AHR triggers a precisely defined and rapid reaction upon binding to endogenous ligands, while the xenobiotic β-naphthoflavone only induces rather unspecific and slow effects. Read More

    Estrogenicity of halogenated bisphenol A: in vitro and in silico investigations.
    Arch Toxicol 2017 Nov 20. Epub 2017 Nov 20.
    College of Food Science and Engineering, Jilin University, Changchun, 130062, China.
    The binding interactions of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to human estrogen receptor α ligand binding domain (hERα-LBD) was investigated using a combined in vitro and in silico approach. First, the recombinant hERα-LBD was prepared as a soluble protein in Escherichia coli BL21(DE3)pLysS. A native fluorescent phytoestrogen, coumestrol, was employed as tracer for the fluorescence polarization assay. Read More

    Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential.
    Arch Toxicol 2017 Nov 20. Epub 2017 Nov 20.
    Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
    Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Read More

    Evaluation of immune-mediated idiosyncratic drug toxicity using chimeric HLA transgenic mice.
    Arch Toxicol 2017 Nov 17. Epub 2017 Nov 17.
    Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8675, Japan.
    Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT. Read More

    Desorption kinetics of organic chemicals from albumin.
    Arch Toxicol 2017 Nov 16. Epub 2017 Nov 16.
    Department of Analytical Environmental Chemistry, Helmholtz Centre for Environmental Research UFZ, Permoserstr. 15, 04318, Leipzig, Germany.
    When present in blood, most chemicals tend to bind to the plasma protein albumin. For distribution into surrounding tissues, desorption from albumin is necessary, because only the unbound form of a chemical is assumed to be able to cross cell membranes. For metabolism of chemicals, the liver is a particularly important organ. Read More

    In vitro biotransformation of pyrrolizidine alkaloids in different species. Part I: Microsomal degradation.
    Arch Toxicol 2017 Nov 16. Epub 2017 Nov 16.
    German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany.
    Pyrrolizidine alkaloids (PA) are secondary metabolites of certain flowering plants. The ingestion of PAs may result in acute and chronic effects in man and livestock with hepatotoxicity, mutagenicity, and carcinogenicity being identified as predominant effects. Several hundred PAs sharing the diol pyrrolizidine as a core structure are formed by plants. Read More

    Sex-specific risk assessment of PFHxS using a physiologically based pharmacokinetic model.
    Arch Toxicol 2017 Nov 16. Epub 2017 Nov 16.
    College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.
    Perfluorohexanesulfonate (PFHxS), which belongs to the group of perfluoroalkyl and polyfluoroalkyl substances (PFASs), has been extensively used in industry and subsequently detected in the environment. Its use may be problematic, as PFHxS is known to induce neuronal cell death, and has been associated with early onset menopause in women and with attention deficit/hyperactivity disorder. Due to these impending issues, the aim of this study is to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for PFHxS in male and female rats, and apply this to a human health risk assessment. Read More

    Transcriptome profile analysis reveals cardiotoxicity of maduramicin in primary chicken myocardial cells.
    Arch Toxicol 2017 Nov 11. Epub 2017 Nov 11.
    Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People's Republic of China.
    Maduramicin, an excellent ionophore antibiotic, is extensively used to control coccidiosis in poultry. Numerous maduramicin intoxications have been reported in farm animal and human due to its relatively narrow safety range, with necrosis or degeneration of cardiac and skeletal muscles as hallmark. To date, the mechanisms of maduramicin-induced cardiotoxicity remain unclear in chicken and other animals. Read More

    Correction to: An appraisal of critical effect sizes for the benchmark dose approach to assess dose-response relationships in genetic toxicology.
    Arch Toxicol 2017 Nov 11. Epub 2017 Nov 11.
    Pharmaceutical Sciences, pRED Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
    In the original publication, Table 1 was incorrect (differences in the numerators of the fractions). The correct version of Table 1 (sums in the numerators) is given below. Read More

    Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.
    Arch Toxicol 2017 Nov 10. Epub 2017 Nov 10.
    European Commission, Joint Research Centre (JRC), 21027, Ispra, Italy.
    Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. Read More

    Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.
    Arch Toxicol 2017 Nov 10. Epub 2017 Nov 10.
    Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, 74100, Ness Ziona, Israel.
    VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. Read More

    Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines.
    Arch Toxicol 2017 Nov 8. Epub 2017 Nov 8.
    Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
    Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0. Read More

    Palytoxin congeners.
    Arch Toxicol 2017 Nov 7. Epub 2017 Nov 7.
    Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.
    Palytoxin, isolated from a zoanthid of the genus Palythoa, is the most potent marine toxin known. Intoxication by palytoxin leads to vasoconstriction, hemorrhage, ataxia, muscle weakness, ventricular fibrillation, pulmonary hypertension, ischemia and death. Palytoxin and its numerous derivatives (congeners) may enter the food chain and accumulate mainly in fishes and crabs, causing severe human intoxication and death following ingestion of contaminated products. Read More

    A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells.
    Arch Toxicol 2017 Nov 6. Epub 2017 Nov 6.
    In Vitro Toxicology Group, Institute of Life Science 1, Singleton Campus, Swansea University Medical School, Swansea University, Swansea, SA2 8PP, UK.
    Human exposure to carcinogens occurs via a plethora of environmental sources, with 70-90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. Read More

    Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A.
    Arch Toxicol 2017 Nov 2. Epub 2017 Nov 2.
    Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany.
    Ochratoxin A (OTA) is a potent renal carcinogen but its mechanism has not been fully resolved. In vitro and in vivo gene expression studies consistently revealed down-regulation of gene expression as the predominant transcriptional response to OTA. Based on the importance of specific histone acetylation marks in regulating gene transcription and our recent finding that OTA inhibits histone acetyltransferases (HATs), leading to loss of acetylation of histones and non-histone proteins, we hypothesized that OTA-mediated repression of gene expression may be causally linked to HAT inhibition and loss of histone acetylation. Read More

    Effect of six oximes on acutely anticholinesterase inhibitor-induced oxidative stress in rat plasma and brain.
    Arch Toxicol 2017 Nov 2. Epub 2017 Nov 2.
    Department of Toxicology "Akademik Danilo Soldatović", Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia.
    Beside the key inhibition of acetylcholinesterase (AChE), involvement of oxidative stress in organophosphate (OP)-induced toxicity has been supported by experimental and human studies. On the other hand, according to our best knowledge, possible antioxidant properties of oximes, the only causal antidotes to OP-inhibited AChE, have been examined only by a few studies. Thus, we have determined the effect of four conventional (obidoxime, trimedoxime, pralidoxime, asoxime) and two promising experimental oximes (K027, K203) on dichlorvos (DDVP)-induced oxidative changes in vivo. Read More

    Comparative developmental toxicity of a comprehensive suite of polycyclic aromatic hydrocarbons.
    Arch Toxicol 2017 Nov 1. Epub 2017 Nov 1.
    Department of Environmental and Molecular Toxicology, Oregon State University, ALS 1007, Corvallis, OR, 97331, USA.
    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. Read More

    Changes in the expression of genes involved in the ovarian function of rats caused by daily exposure to 3-methylcholanthrene and their prevention by α-naphthoflavone.
    Arch Toxicol 2017 Nov 1. Epub 2017 Nov 1.
    Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina, Paraguay 2155, 16º P, (C1121ABG) Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
    Daily exposure to low doses of 3-methylcholanthrene (3MC) during the pubertal period in rats disrupts both follicular growth and ovulation. Thus, to provide new insights into the toxicity mechanism of 3MC in the ovary, here we investigated the effect of daily exposure to 3MC on selected ovarian genes, the role of the aryl hydrocarbon receptor (AhR) and the level of epigenetic remodeling of histone post-transcriptional modifications. Immature rats were daily injected with 3MC (0. Read More

    Activation of insulin-like growth factor 1 receptor participates downstream of GPR30 in estradiol-17β-D-glucuronide-induced cholestasis in rats.
    Arch Toxicol 2017 Oct 31. Epub 2017 Oct 31.
    Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas (CONICET-U.N.R.), Suipacha 570, S2002LRL, Rosario, Argentina.
    Estradiol-17β-D-glucuronide (E17G), through the activation of different signaling proteins, induces acute endocytic internalization of canalicular transporters in rat, including multidrug resistance-associated protein 2 (Abcc2) and bile salt export pump (Abcb11), generating cholestasis. Insulin-like growth factor 1 receptor (IGF-1R) is a membrane-bound tyrosine kinase receptor that can potentially interact with proteins activated by E17G. The aim of this study was to analyze the potential role of IGF-1R in the effects of E17G in isolated perfused rat liver (IPRL) and isolated rat hepatocyte couplets. Read More

    Correction to: Quantification of N-phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions.
    Arch Toxicol 2017 Nov;91(11):3597
    Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Ruhr-University Bochum (IPA), Burkle-de-la-Camp Platz 1, 44789, Bochum, Germany.
    The article 'Quantification of N-phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions' written by Heiko Udo Käfferlein, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 12th September 2017 without open access. Read More

    Predicting in vivo effect levels for repeat-dose systemic toxicity using chemical, biological, kinetic and study covariates.
    Arch Toxicol 2017 Oct 27. Epub 2017 Oct 27.
    National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
    In an effort to address a major challenge in chemical safety assessment, alternative approaches for characterizing systemic effect levels, a predictive model was developed. Systemic effect levels were curated from ToxRefDB, HESS-DB and COSMOS-DB from numerous study types totaling 4379 in vivo studies for 1247 chemicals. Observed systemic effects in mammalian models are a complex function of chemical dynamics, kinetics, and inter- and intra-individual variability. Read More

    Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans.
    Arch Toxicol 2017 Oct 24. Epub 2017 Oct 24.
    National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, 72079, USA.
    Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. Read More

    Metal chelators and neurotoxicity: lead, mercury, and arsenic.
    Arch Toxicol 2017 Oct 24. Epub 2017 Oct 24.
    Faculty of Public Health, Inland Norway University of Applied Sciences, Elverum, Norway.
    This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Read More

    PFOS induces proliferation, cell-cycle progression, and malignant phenotype in human breast epithelial cells.
    Arch Toxicol 2017 Oct 23. Epub 2017 Oct 23.
    Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
    Perfluorooctanesulfonic acid (PFOS) is a synthetic fluorosurfactant widely used in the industry and a prominent environmental toxicant. PFOS is persistent, bioaccumulative, and toxic to mammalian species. Growing evidence suggests that PFOS has the potential to interfere with estrogen homeostasis, posing a risk of endocrine-disrupting effects. Read More

    Effects of arsenolipids on in vitro blood-brain barrier model.
    Arch Toxicol 2017 Oct 20. Epub 2017 Oct 20.
    Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
    Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood-brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood-brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood-brain barrier). Read More

    Acute regulation of multidrug resistance-associated protein 2 localization and activity by cAMP and estradiol-17β-D-glucuronide in rat intestine and Caco-2 cells.
    Arch Toxicol 2017 Oct 20. Epub 2017 Oct 20.
    Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000, Rosario, Argentina.
    Multidrug resistance-associated protein 2 (MRP2) is an ATP-dependent transporter expressed at the brush border membrane of the enterocyte that confers protection against absorption of toxicants from foods or bile. Acute, short-term regulation of intestinal MRP2 activity involving changes in its apical membrane localization was poorly explored. We evaluated the effects of dibutyryl-cAMP (db-cAMP), a permeable analog of cAMP, and estradiol-17β-D-glucuronide (E217G), an endogenous derivative of estradiol, on MRP2 localization and activity using isolated rat intestinal sacs and Caco-2 cells, a model of human intestinal epithelium. Read More

    Adverse outcome pathways: opportunities, limitations and open questions.
    Arch Toxicol 2017 Nov 19;91(11):3477-3505. Epub 2017 Oct 19.
    Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, Germany.
    Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. Read More

    Roles of cytosolic phospholipase A2α in reproductive and systemic toxicities in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed mice.
    Arch Toxicol 2017 Oct 17. Epub 2017 Oct 17.
    Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a variety of toxicities upon binding of TCDD to aryl hydrocarbon receptor. Although this binding upregulates the synthesis of prostaglandins and their related lipid mediators via cytosolic phospholipase A2α (cPLA2α), toxicological significance of this signaling pathway remains elusive. Herein, we investigated the roles of cPLA2α in TCDD toxicities using cPLA2α-null mice. Read More

    Arylamine N-acetyltransferase 1 in situ N-acetylation on CD3+ peripheral blood mononuclear cells correlate with NATb mRNA and NAT1 haplotype.
    Arch Toxicol 2017 Oct 17. Epub 2017 Oct 17.
    Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, San Luis Potosí, Mexico.
    Human arylamine N-acetyltransferase 1 (NAT1) is responsible for the activation and elimination of xenobiotic compounds and carcinogens. Genetic polymorphisms in NAT1 modify both drug efficacy and toxicity. Previous studies have suggested a role for NAT1 in the development of several diseases. Read More

    GABAA receptor subtype selectivity of the proconvulsant rodenticide TETS.
    Arch Toxicol 2017 Oct 16. Epub 2017 Oct 16.
    Department of Pharmacology, Genome and Biomedical Sciences Facility Room 3502, 451 Health Sciences Drive, School of Medicine, University of California, Davis, CA, 95616, USA.
    The rodenticide tetramethylenedisulfotetramine (TETS) is a potent convulsant (lethal dose in humans 7-10 mg) that is listed as a possible threat agent by the United States Department of Homeland Security. TETS has previously been studied in vivo for toxicity and in vitro in binding assays, with the latter demonstrating it to be a non-competitive antagonist on GABAA receptors. To determine whether TETS exhibits subtype selectivity for a particular GABAA receptor combination, we used whole-cell patch-clamp to determine the potency of TETS on the major synaptic and extrasynaptic GABAA receptors associated with convulsant activity. Read More

    Hepatotoxic combination effects of three azole fungicides in a broad dose range.
    Arch Toxicol 2017 Oct 16. Epub 2017 Oct 16.
    German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
    Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. Read More

    Respiratory sensitization: toxicological point of view on the available assays.
    Arch Toxicol 2017 Oct 16. Epub 2017 Oct 16.
    Department of Environmental Toxicology, University Trier, Universitätsring 15, 54296, Trier, Germany.
    Respiratory sensitization as a consequence of exposure to chemical products has increased over the last decades, leading to an increase of morbidity. The increased use of synthetic compounds resulted in an exponential growth of substances to which we are potentially exposed on a daily basis. Some of them are known to induce respiratory sensitization, meaning that they can trigger the development of allergies. Read More

    Evidence for a complex formation between CYP2J5 and mEH in living cells by FRET analysis of membrane protein interaction in the endoplasmic reticulum (FAMPIR).
    Arch Toxicol 2017 Nov 13;91(11):3561-3570. Epub 2017 Oct 13.
    Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
    The potential complex formation between microsomal epoxide hydrolase (mEH) and cytochrome P450-dependent monooxygenase (CYP) has been a subject of research for many decades. Such an association would enable efficient substrate channeling between CYP and mEH and as such represent an attractive strategy to prevent deleterious accumulation of harmful metabolic by-products such as CYP-generated epoxide intermediates. However, such complex formation is experimentally difficult to prove, because CYP and mEH are membrane-bound proteins that are prone to unspecific aggregation after solubilization. Read More


    Novel treatment opportunities for sulfur mustard-related cancers: genetic and epigenetic perspectives.
    Arch Toxicol 2017 Oct 10. Epub 2017 Oct 10.
    Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
    Sulfur mustard (SM), also known as mustard gas, is a chemical weapon which by now has been used in many wars. The most concerning SM toxic effect is probable carcinogenicity. In this study, the genetic and epigenetic mechanisms of SM carcinogenicity, by focusing on treatment of SM-associated malignancies, particularly gene therapeutics, cancer vaccines, and epigenetic medications, have been criticized. Read More

    Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants.
    Arch Toxicol 2017 Oct 9. Epub 2017 Oct 9.
    Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
    Probiotics have been explored to stimulate gut health in weaned pigs, when they started to consume solid diet where mycotoxins could be present. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus RC007 on the intestinal toxicity of deoxynivalenol (DON) in an ex vivo model. Jejunal explants, obtained from 5-week-old crossbred castrated male piglets, were kept as control, exposed for 3 h to 10 μM DON, incubated for 4 h with 10(9) CFU/mL L. Read More

    ROS generation and JNK activation contribute to 4-methoxy-TEMPO-induced cytotoxicity, autophagy, and DNA damage in HepG2 cells.
    Arch Toxicol 2017 Oct 9. Epub 2017 Oct 9.
    Division of Molecular and Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR, 72079, USA.
    4-Methoxy-TEMPO, a derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), is a stable nitroxide radical and is generally used in organic and pharmaceutical syntheses for the oxidation of alcohols. Previously, we reported the involvement of reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) in TEMPO-induced apoptosis in mouse L5178Y cells. In this study, we investigated 4-methoxy-TEMPO induced toxicity in human HepG2 hepatoma cells and its underlying mechanisms. Read More

    The effects of the obesogen tributyltin on the metabolism of Sertoli cells cultured ex vivo.
    Arch Toxicol 2017 Oct 9. Epub 2017 Oct 9.
    Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Rua Marquês d'Ávila e Bolama, Av. Infante D. Henrique, 6200-001, Covilhã, Portugal.
    Human exposure to environmental contaminants is widespread. Some of these contaminants have the ability to interfere with adipogenesis, being thus considered as obesogens. Recently, obesogens have been singled out as a cause of male infertility. Read More

    Protective effects of the resveratrol analog piceid in dopaminergic SH-SY5Y cells.
    Arch Toxicol 2017 Oct 4. Epub 2017 Oct 4.
    Division of Pharmaceutical Sciences, Department of Pharmacology, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
    Age-related motor deficits, such as loss of balance and coordination, are caused, in part, by loss of dopaminergic neurons. Oxidative stress is known to play a role in this neuronal loss. Resveratrol, a natural antioxidant with anticancer and anti-inflammatory potential, has been shown to protect dopaminergic-like cells (SH-SY5Y) against oxidative stress. Read More

    Erratum to: Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells.
    Arch Toxicol 2017 Nov;91(11):3645
    Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, Scotland, UK.
    During manuscript proofing, the following sentence was not deleted in the section "Results" at the end of the paragraph: "Both male and female hepatocytes responded in a similar fashion to cotinine, whereas male hepatocyte function was more sensitive to chrysene, fluorene and naphthalene than female hepatocytes". Read More

    t-BuOOH induces ferroptosis in human and murine cell lines.
    Arch Toxicol 2017 Oct 3. Epub 2017 Oct 3.
    Institute of Toxicology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacherstr. 67, 55131, Mainz, Germany.
    Reactive oxygen species (ROS)-induced apoptosis has been extensively studied. Increasing evidence suggests that ROS, for instance, induced by hydrogen peroxide (H2O2), might also trigger regulated necrotic cell death pathways. Almost nothing is known about the cell death pathways triggered by tertiary-butyl hydroperoxide (t-BuOOH), a widely used inducer of oxidative stress. Read More

    Obesogenic endocrine disruptors and obesity: myths and truths.
    Arch Toxicol 2017 Nov 3;91(11):3469-3475. Epub 2017 Oct 3.
    Department of Clinical Medicine and Surgery, University "Federico II" - Naples, 80131, Naples, Italy.
    Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products. The window of life during which the exposure happens could lead to different effects. Read More

    Beyond detoxification: a role for mouse mEH in the hepatic metabolism of endogenous lipids.
    Arch Toxicol 2017 Nov 3;91(11):3571-3585. Epub 2017 Oct 3.
    Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
    Microsomal and soluble epoxide hydrolase (mEH and sEH) fulfill apparently distinct roles: Whereas mEH detoxifies xenobiotics, sEH hydrolyzes fatty acid (FA) signaling molecules and is thus implicated in a variety of physiological functions. These epoxy FAs comprise epoxyeicosatrienoic acids (EETs) and epoxy-octadecenoic acids (EpOMEs), which are formed by CYP epoxygenases from arachidonic acid (AA) and linoleic acid, respectively, and then are hydrolyzed to their respective diols, the so-called DHETs and DiHOMEs. Although EETs and EpOMEs are also substrates for mEH, its role in lipid signaling is considered minor due to lower abundance and activity relative to sEH. Read More

    Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells.
    Arch Toxicol 2017 Sep 30. Epub 2017 Sep 30.
    BASF SE Experimental Toxicology and Ecology, Carl-Bosch Str.38, 67056, Ludwigshafen Am Rhein, Germany.
    Liver toxicity is a leading systemic toxicity of drugs and chemicals demanding more human-relevant, high throughput, cost effective in vitro solutions. In addition to contributing to animal welfare, in vitro techniques facilitate exploring and understanding the molecular mechanisms underlying toxicity. New 'omics technologies can provide comprehensive information on the toxicological mode of action of compounds, as well as quantitative information about the multi-parametric metabolic response of cellular systems in normal and patho-physiological conditions. Read More

    Arsenite and methylarsonite inhibit mitochondrial metabolism and glucose-stimulated insulin secretion in INS-1 832/13 β cells.
    Arch Toxicol 2017 Sep 27. Epub 2017 Sep 27.
    Department of Nutrition, CB# 74612, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599-7461, USA.
    Growing evidence suggests that exposure to environmental contaminants contributes to the current diabetes epidemic. Inorganic arsenic (iAs), a drinking water and food contaminant, is one of the most widespread environmental diabetogens according to epidemiological studies. Several schemes have been proposed to explain the diabetogenic effects of iAs exposure; however, the exact mechanism remains unknown. Read More

    Toxicokinetic of tris(2-butoxyethyl) phosphate (TBOEP) in humans following single oral administration.
    Arch Toxicol 2017 Sep 27. Epub 2017 Sep 27.
    Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority, Pfarrstrasse 3, 80538, Munich, Germany.
    Tris(2-butoxyethyl) phosphate (TBOEP; 20 µg/kg b.w.) was orally administered to three female and three male volunteers. Read More

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