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    6810 results match your criteria Archives of Toxicology[Journal]

    1 OF 137

    Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.
    Arch Toxicol 2017 Sep 20. Epub 2017 Sep 20.
    Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Rua Câmara Pestana 6, 1150-082, Lisbon, Portugal.
    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Read More

    Immediate responses of the cockroach Blaptica dubia after the exposure to sulfur mustard.
    Arch Toxicol 2017 Sep 20. Epub 2017 Sep 20.
    Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany.
    The chemical agent sulfur mustard (SM) causes erythema, skin blisters, ulcerations, and delayed wound healing. It is accepted that the underlying molecular toxicology is based on DNA alkylation. With an expected delay, DNA damage causes impairment of protein biosynthesis and disturbance of cell division. Read More

    Current pesticide dietary risk assessment in light of comparable animal study NOAELs after chronic and short-termed exposure durations.
    Arch Toxicol 2017 Sep 19. Epub 2017 Sep 19.
    Federal Food Safety and Veterinary Office (FSVO), Risk Assessment Division, Schwarzenburgstrasse 155, 3003, Bern, Switzerland.
    Dietary risk assessment (DRA) of pesticides includes the estimation of chronic and acute exposures from crop residues, but assesses acute exposures only for pesticides with an acute reference dose (ARfD). Acute estimation uses high percentiles of food consumption surveys which are considerably higher than per capita lifetime averaged food consumption values which are used for chronic estimations. Assessing acute risks only for pesticides with an ARfD tacitly assumes that chronic risk assessment covers also intermittent occurring exposures which could significantly exceed chronic estimates. Read More

    Urinary excretion kinetics of the metabolite N-methylmalonamic acid (NMMA) after oral dosage of chloromethylisothiazolinone and methylisothiazolinone in human volunteers.
    Arch Toxicol 2017 Sep 19. Epub 2017 Sep 19.
    Institute for Occupational and Social Medicine, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
    Methylisothiazolinone (MI) as well as the mixture of chloromethylisothiazolinone/methyl-iso-thiazolinone (MCI/MI, 3:1) are widespread biocides used in personal care products with potential consumer exposure. Their use is currently under discussion because of rising rates of skin sensitization against these substances in the general population. We have examined the human metabolism of methylisothiazolinone and chloromethylisothiazolinone after oral dosage of stable isotope-labelled analogues. Read More

    Rho-inhibiting C2IN-C3 fusion toxin inhibits chemotactic recruitment of human monocytes ex vivo and in mice in vivo.
    Arch Toxicol 2017 Sep 18. Epub 2017 Sep 18.
    Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
    Bacterial protein toxins became valuable molecular tools for the targeted modulation of cell functions in experimental pharmacology and attractive therapeutics because of their potent and specific mode of action in human cells. C2IN-C3lim, a recombinant fusion toxin (~50 kDa) of the Rho-inhibiting C3lim from Clostridium (C.) limosum and a non-toxic portion of the C. Read More

    Alterations in epididymal proteomics and antioxidant activity of mice exposed to fluoride.
    Arch Toxicol 2017 Sep 16. Epub 2017 Sep 16.
    College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, China.
    It is well known that high fluoride results in low fertility. Epididymis is the important place for spermatozoa maturation, which is essential for successful fertilization. In the previous studies, fluoride was reported to damage the epididymal structure of mouse and rabbit. Read More

    CoQ0-induced mitochondrial PTP opening triggers apoptosis via ROS-mediated VDAC1 upregulation in HL-60 leukemia cells and suppresses tumor growth in athymic nude mice/xenografted nude mice.
    Arch Toxicol 2017 Sep 16. Epub 2017 Sep 16.
    Institute of Nutrition, College of Pharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan.
    Coenzyme Q (CoQ) analogs with variable numbers of isoprenoid units have been demonstrated as anticancer and antioxidant/pro-oxidant molecules. This study examined the in vitro and in vivo antitumor and apoptosis activities of CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero isoprenoid side-chains) through upregulation of the Voltage-dependent anion channel 1 (VDAC1) signaling pathway on human promyelocytic leukemia. CoQ0 (0-40 μg/mL) treatment significantly reduced HL-60 cell viability, and up-regulated mitochondrial VDAC1 expression. Read More

    Early life arsenic exposure, infant and child growth, and morbidity: a systematic review.
    Arch Toxicol 2017 Sep 14. Epub 2017 Sep 14.
    Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden.
    Epidemiological studies have suggested a negative association between early life arsenic exposure and fetal size at birth, and subsequently with child morbidity and growth. However, our understanding of the relationship between arsenic exposure and morbidity and growth is limited. This paper aims to systematically review original human studies with an analytical epidemiological study design that have assessed arsenic exposure in fetal life or early childhood and evaluated the association with one or several of the following outcomes: fetal growth, birth weight or other birth anthropometry, infant and child growth, infectious disease morbidity in infancy and early childhood. Read More

    Hepatotoxicity of monoterpenes and sesquiterpenes.
    Arch Toxicol 2017 Sep 13. Epub 2017 Sep 13.
    Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005, Hradec Králové, Czech Republic.
    Public interest in natural therapies has increased significantly over past decades. Herbs and herbal products are extensively consumed worldwide and they are generally considered as safe. However, this may not always be true as many cases of herb-induced liver injury are reported every year. Read More

    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 Sep 12. Epub 2017 Sep 12.
    Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Ruhr-University Bochum (IPA), Bürkle-de-la-Camp Platz 1, 44789, Bochum, Germany.
    N-Phenyl-2-naphthylamine (P2NA) is an antioxidant used to protect rubbers from flex-cracking. P2NA can be converted in vivo to 2NA, one of the most potent bladder carcinogens. Here, we report the specific and ultra-sensitive quantification of P2NA in the receptor fluid of Franz diffusion cells by gas chromatography and isotope-dilution tandem-mass spectroscopy (GC-MS/MS). Read More

    Developmental exposure of decabromodiphenyl ether impairs subventricular zone neurogenesis and morphology of granule cells in mouse olfactory bulb.
    Arch Toxicol 2017 Sep 7. Epub 2017 Sep 7.
    College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, People's Republic of China.
    Polybrominated diphenyl ethers (PBDEs) are additive flame retardants widely used in various products (e.g., textiles, consumer electronics, and plastics). Read More

    Investigations on the dose-response relationship of combined exposure to low doses of three anti-androgens in Wistar rats.
    Arch Toxicol 2017 Sep 6. Epub 2017 Sep 6.
    Experimental Toxicology and Ecology, BASF SE, 67056, Ludwigshafen, Germany.
    The current investigation examines whether combined exposure to three anti-androgens (flutamide, prochloraz, vinclozolin) result in interference with endocrine homeostasis when applied at very low dose levels, and whether the results of combined exposure are more pronounced than to the individual compounds. A pre-post-natal in vivo study design was chosen with more parameters than regulatory testing protocols require (additional endpoints addressing hormone levels, morphology and histopathological examinations). Dose levels were chosen to represent the lowest observed adverse effect level (LOAEL), the no observed adverse effect level (NOAEL), and the acceptable daily intake for each individual substance. Read More

    Bisphenol A exposure perturbs visual function of adult cats by remodeling the neuronal activity in the primary visual pathway.
    Arch Toxicol 2017 Sep 5. Epub 2017 Sep 5.
    CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People's Republic of China.
    Bisphenol A (BPA), a common environmental xenoestrogen, has been implicated in physiological and behavioral impairment, but the neuronal basis remains elusive. Although various synaptic mechanisms have been shown to mediate BPA-induced brain deficits, there are almost no reports addressing its underlying physiological mechanisms at the individual neuron level, particularly in the primary visual system. In the present study, using multiple-channel recording technique, we recorded the responses of single neurons in the primary visual system of cats to various direction stimuli both before and after BPA exposure. Read More

    Specific effects of prenatal DEHP exposure on neuroendocrine gene expression in the developing hypothalamus of male rats.
    Arch Toxicol 2017 Sep 4. Epub 2017 Sep 4.
    Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, No. 22 Qixiangtai Rd., Heping Dist., Tianjin, 300070, People's Republic of China.
    Endocrine disrupting chemicals may disrupt developing neuroendocrine systems, especially when the exposure occurs during a critical period. This study aimed to investigate whether prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a major component of plasticizers used worldwide, disrupted the development of a network of genes important for neuroendocrine function in male rats. Pregnant rats were treated with corn oil (vehicle control), 2, 10 or 50 mg/kg DEHP by gavage from gestational day 14 to 19. Read More

    Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity.
    Arch Toxicol 2017 Sep 4. Epub 2017 Sep 4.
    School of Pharmaceutical Sciences, Tsinghua University, 100084, Beijing, China.
    Zoledronate is a bisphosphonate that is widely used in the treatment of metabolic bone diseases. However, zoledronate induces significant nephrotoxicity associated with acute tubular necrosis and renal fibrosis when administered intravenously. There is speculation that zoledronate-induced nephrotoxicity may result from its pharmacological activity as an inhibitor of the mevalonate pathway but the molecular mechanisms are not fully understood. Read More

    Selective determination of mandelic acid in urine using molecularly imprinted polymer in microextraction by packed sorbent.
    Arch Toxicol 2017 Sep 4. Epub 2017 Sep 4.
    Department of Occupational Health, School of Public Health, Hamadan University of Medical Sciences, PO Box 65175-4171, Hamadan, 6517838695, Iran.
    Mandelic acid (MA) is a major metabolite of ethylbenzene and styrene. For the first time, a selective, fast, and easy-to-use procedure was developed for the determination of MA in urine samples. The new procedure is based on MIMEPS, the combination of a molecularly imprinted polymer (MIP) and microextraction by packed sorbent (MEPS). Read More

    Early response of glutathione- and thioredoxin-dependent antioxidant defense systems to Tl(I)- and Tl(III)-mediated oxidative stress in adherent pheochromocytoma (PC12adh) cells.
    Arch Toxicol 2017 Sep 2. Epub 2017 Sep 2.
    Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
    Thallium (Tl) is a toxic heavy metal that causes oxidative stress both in vitro and in vivo. In this work, we evaluated the production of oxygen (ROS)- and nitrogen (RNS)-reactive species in adherent PC12 (PC12adh) cells exposed for 0.5-6 h to Tl(I) or Tl(III) (10-100 µM). Read More

    Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein.
    Arch Toxicol 2017 Sep 1. Epub 2017 Sep 1.
    Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
    Although shorter chain homologues and other types of fluorinated chemicals are currently used as alternatives to long-chain perfluoroalkyl substances (PFASs), their safety information remains unclear and urgently needed. Here, the cytotoxicity of several fluorinated alternatives (i.e. Read More

    Toxicological interactions of pesticide mixtures: an update.
    Arch Toxicol 2017 Aug 28. Epub 2017 Aug 28.
    Andalulsian School of Public Health, Granada, Spain.
    Pesticides can interact with each other in various ways according to the compound itself and its chemical family, the dose and the targeted organs, leading to various effects. The term interaction means situations where some or all individual components of a mixture influence each other's toxicity and the joint effects may deviate from the additive predictions. The various mixture effects can be greatly determined by toxicokinetic and toxicodynamic factors involving metabolic pathways and cellular or molecular targets of individual pesticides, respectively. Read More

    A frequent misinterpretation in current research on liver fibrosis: the vessel in the center of CCl4-induced pseudolobules is a portal vein.
    Arch Toxicol 2017 Aug 19. Epub 2017 Aug 19.
    Molecular Hepatology Section, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
    Carbon tetrachloride-induced liver injury is a thoroughly studied model for regeneration and fibrosis in rodents. Nevertheless, its pattern of liver fibrosis is frequently misinterpreted as portal type. To clarify this, we show that collagen type IV(+) "streets" and α-SMA(+) cells accumulate pericentrally and extend to neighbouring central areas of the liver lobule, forming a 'pseudolobule'. Read More

    Developmental neurotoxicity of the hippocampus following in utero exposure to methylmercury: impairment in cell signaling.
    Arch Toxicol 2017 Aug 18. Epub 2017 Aug 18.
    Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600 Anexo, Porto Alegre, RS, 90035-003, Brazil.
    In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2. Read More

    An appraisal of critical effect sizes for the benchmark dose approach to assess dose-response relationships in genetic toxicology.
    Arch Toxicol 2017 Aug 10. Epub 2017 Aug 10.
    Pharmaceutical Sciences, pRED Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.
    The benchmark dose (BMD) concept is increasingly utilized to analyze quantitative dose-response relationships in genetic toxicology. This methodology requires the user (i.e. Read More

    Long-term exposure of immortalized keratinocytes to arsenic induces EMT, impairs differentiation in organotypic skin models and mimics aspects of human skin derangements.
    Arch Toxicol 2017 Aug 3. Epub 2017 Aug 3.
    Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center Vienna, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
    Arsenic is one of the most important human carcinogens and environmental pollutants. However, the evaluation of the underlying carcinogenic mechanisms is challenging due to the lack of suitable in vivo and in vitro models, as distinct interspecies differences in arsenic metabolism exist. Thus, it is of high interest to develop new experimental models of arsenic-induced skin tumorigenesis in humans. Read More

    Screening the ToxCast phase II libraries for alterations in network function using cortical neurons grown on multi-well microelectrode array (mwMEA) plates.
    Arch Toxicol 2017 Aug 2. Epub 2017 Aug 2.
    Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, MD105-05, Research Triangle Park, NC, 27711, USA.
    Methods are needed for rapid screening of environmental compounds for neurotoxicity, particularly ones that assess function. To demonstrate the utility of microelectrode array (MEA)-based approaches as a rapid neurotoxicity screening tool, 1055 chemicals from EPA's phase II ToxCast library were evaluated for effects on neural function and cell health. Primary cortical networks were grown on multi-well microelectrode array (mwMEA) plates. Read More

    Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury.
    Arch Toxicol 2017 Jul 31. Epub 2017 Jul 31.
    Unidad de Hepatología Experimental, Torre A, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av Fernando Abril Martorell 106, 46026, Valencia, Spain.
    Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. Read More

    Consequences of bisphenol a perinatal exposure on immune responses and gut barrier function in mice.
    Arch Toxicol 2017 Jul 21. Epub 2017 Jul 21.
    Intestinal Development, Xenobiotics and ImmunoToxicology, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
    The potent immunomodulatory effect of the endocrine disruptor bisphenol A during development and consequences during life span are of increasing concern. Particular interests have been raised from animal studies regarding the risk of developing food intolerance and infection. We aimed to identify immune disorders in mice triggered by perinatal exposure to bisphenol A. Read More

    Down-regulation of miRNA-451a and miRNA-486-5p involved in benzene-induced inhibition on erythroid cell differentiation in vitro and in vivo.
    Arch Toxicol 2017 Jul 21. Epub 2017 Jul 21.
    Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
    Exposure to high-dose benzene leads to the inhibition of erythroid differentiation. However, whether lower doses of benzene exposure resemble high-dose effects in erythroid differentiation, as well as the underlying mechanisms, remains largely unknown. To identify the microRNAs (miRNAs) specifically responsible for benzene exposure and their regulatory role in erythroid differentiation, we performed miRNA microarray in CD34(+) hematopoietic progenitor cells isolated from human umbilical cord blood after treatment with hydroquinone (HQ), a metabolite of benzene at concentrations of 0, 1. Read More

    Erratum to: Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells.
    Arch Toxicol 2017 Jul 21. Epub 2017 Jul 21.
    Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, Scotland, UK.

    Carbofuran causes neuronal vulnerability to glutamate by decreasing GluA2 protein levels in rat primary cortical neurons.
    Arch Toxicol 2017 Jul 19. Epub 2017 Jul 19.
    Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
    Glutamate receptor 2 (GluA2/GluR2) is one of the four subunits of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR); an increase in GluA2-lacking AMPARs contributes to neuronal vulnerability to excitotoxicity because of the receptor's high Ca(2+) permeability. Carbofuran is a carbamate pesticide used in agricultural areas to increase crop productivity. Due to its broad-spectrum action, carbofuran has also been used as an insecticide, nematicide, and acaricide. Read More

    Selectivity of plasma membrane calcium ATPase (PMCA)-mediated extrusion of toxic divalent cations in vitro and in cultured cells.
    Arch Toxicol 2017 Jul 18. Epub 2017 Jul 18.
    Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Junín 956, Ciudad Autónoma de Buenos Aires, C1113AAD, Argentina.
    In the recent years, the toxicity of certain divalent cations has been associated with the alteration of intracellular Ca(2+) homeostasis. Among other mechanisms, these cations may affect the functionality of certain Ca(2+)-binding proteins and/or Ca(2+) pumps. The plasma membrane calcium pump (PMCA) maintains Ca(2+) homeostasis in eukaryotic cells by mediating the efflux of this cation in a process coupled to ATP hydrolysis. Read More

    A review of drug-induced liver injury databases.
    Arch Toxicol 2017 Jul 17. Epub 2017 Jul 17.
    School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, People's Republic of China.
    Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB. Read More

    Rac1-mediated cardiac damage causes diastolic dysfunction in a mouse model of subacute doxorubicin-induced cardiotoxicity.
    Arch Toxicol 2017 Jul 14. Epub 2017 Jul 14.
    Medical Faculty, Institute of Toxicology, Heinrich Heine University Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany.
    The anticancer efficacy of anthracyclines is limited by congestive heart failure. Clinically established markers of early onset of cardiotoxicity following anthracycline treatment and preventive measures are missing. Although statins are reported to alleviate anthracycline-induced cardiotoxicity in vivo, the molecular mechanisms involved remain elusive. Read More

    Oxidative inactivation of the endogenous antioxidant protein DJ-1 by the food contaminants 3-MCPD and 2-MCPD.
    Arch Toxicol 2017 Jul 13. Epub 2017 Jul 13.
    Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
    3-Chloro-1,2-propanediol (3-MCPD) and 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants being present either as free substances or as fatty acid esters in numerous foods. 3-MCPD was classified to be possibly carcinogenic to humans (category 2B) with kidney and testis being the primary target organs according to animal studies. A previous 28-day oral feeding study with rats revealed that the endogenous antioxidant protein DJ-1 was strongly deregulated at the protein level in kidney, liver, and testis of the experimental animals that had been treated either with 3-MCPD, 2-MCPD or their dipalmitate esters. Read More

    Reply to the Commentary by Lotti M. and Moretto A. "Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown and the unknown.
    Arch Toxicol 2017 Jul 12. Epub 2017 Jul 12.
    Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168th Street Suite 1107B, New York, NY, 10032, USA.

    Toxic effects and biodistribution of ultrasmall gold nanoparticles.
    Arch Toxicol 2017 Jul 12. Epub 2017 Jul 12.
    Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1a, 52074, Aachen, Germany.
    Gold nanoparticles (AuNPs) have been extensively explored in biomedical applications, for example as drug carriers, contrast agents, or therapeutics. However, AuNP can exhibit cytotoxic profile, when the size is below 2 nm (ultrasmall AuNP; usAuNP) and when the stabilizing ligands allow for access to the gold surface either for the direct interaction with biomolecules or for catalytic activity of the unshielded gold surface. Furthermore, usAuNP exhibits significantly different biodistribution and enhanced circulation times compared to larger AuNP. Read More

    Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells.
    Arch Toxicol 2017 Jul 5. Epub 2017 Jul 5.
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.
    The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24 h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). Read More

    Regulation of SIRT1/AMPK axis is critically involved in gallotannin-induced senescence and impaired autophagy leading to cell death in hepatocellular carcinoma cells.
    Arch Toxicol 2017 Jul 4. Epub 2017 Jul 4.
    Cancer Molecular Targeted Herbal Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
    Hepatocellular carcinoma (HCC) is one of the most fatal malignancies with high mortality worldwide. Here the underlying antitumor mechanism of gallotannin was elucidated in HCC cells. Gallotannin suppressed viability and colony formation, increased subG1 portion and also induced senescence via upregulation of p21, G0/G1 arrest and higher SA-β-gal activity in HepG2 and SK-Hep1 cells. Read More

    Lung damage analyzed by machine vision on tissue sections of mice.
    Arch Toxicol 2017 Jul 3. Epub 2017 Jul 3.
    Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.
    The inhalation of environmental toxicants can induce lung damage. Many methods are currently available to analyze lung tissue damage and are based on empirical visual judgment; however, the accuracy of the assessments are influenced by individual differences among pathologists. Here, we establish new methods of analysis for lung tissue sections based on machine vision and verify this new automatic high-flux method with the model of mice inhaling aqueous aerosol with different concentrations of CdCl2 (0, 1, 3, 5 mM 2 h/day) for 7 days through analyses of pulmonary porosity, mucus, pneumonia and co-localized staining. Read More

    Adverse outcome pathways: a concise introduction for toxicologists.
    Arch Toxicol 2017 Jun 28. Epub 2017 Jun 28.
    European Commission, Joint Research Centre (JRC), Ispra, Italy.
    Adverse outcome pathways (AOPs) are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology, and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use AOPs, have been published in the last few years. Read More

    Genotoxicity testing of different surface-functionalized SiO2, ZrO2 and silver nanomaterials in 3D human bronchial models.
    Arch Toxicol 2017 Jun 22. Epub 2017 Jun 22.
    Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
    Inhalation is considered a critical uptake route for NMs, demanding for sound toxicity testing using relevant test systems. This study investigates cytotoxicity and genotoxicity in EpiAirway™ 3D human bronchial models using 16 well-characterized NMs, including surface-functionalized 15 nm SiO2 (4 variants), 10 nm ZrO2 (4), and nanosilver (3), ZnO NM-110, TiO2 NM-105, BaSO4 NM-220, and two AlOOH NMs. Cytotoxicity was assessed by LDH and ATP assays and genotoxicity by the alkaline comet assay. Read More

    Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.
    Arch Toxicol 2017 Jun 21. Epub 2017 Jun 21.
    Christian Doppler Laboratory for Mycotoxin Metabolism, Department of Agrobiotechnology (IFA-Tulln), Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430, Tulln, Austria.
    The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. Read More

    A nationwide study of the incidence rate of herb-induced liver injury in Korea.
    Arch Toxicol 2017 Jun 20. Epub 2017 Jun 20.
    Hepatology Department, Daejeon Oriental Hospital of Daejeon University, 176-9 Daeheung-ro, Jung-gu, Daejeon, 34929, South Korea.
    Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. Read More

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