7,187 results match your criteria Archives of Toxicology[Journal]


Ablation of aryl hydrocarbon receptor promotes angiotensin II-induced cardiac fibrosis through enhanced c-Jun/HIF-1α signaling.

Arch Toxicol 2019 Apr 23. Epub 2019 Apr 23.

Nagoya University Graduate School of Medicine, Nagoya, Japan.

Aryl hydrocarbon receptor (AHR) is a transcription factor that binds to DNA as a heterodimer with the AHR nuclear translocator (ARNT) after interaction with ligands, such as polycyclic and halogenated aromatic hydrocarbons and other xenobiotics. The endogenous ligands and functions of AHR have been the subject of many investigations. In the present study, the potential role of AHR signaling in the development of left ventricular hypertrophy and cardiac fibrosis by angiotensin II (Ang II) infusion was investigated in mice lacking the AHR gene (Ahr). Read More

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http://dx.doi.org/10.1007/s00204-019-02446-1DOI Listing

A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells.

Arch Toxicol 2019 Apr 23. Epub 2019 Apr 23.

College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.

Avobenzone is the most commonly used ultraviolet (UV) A filter ingredient in sunscreen. To investigate the biological activity of avobenzone in normal human epidermal keratinocytes (NHEKs), the genome-scale transcriptional profile of NHEKs was performed. In this microarray study, we found 273 up-regulated and 274 down-regulated differentially expressed genes (DEGs) in NHEKs treated with avobenzone (10 μM). Read More

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http://dx.doi.org/10.1007/s00204-019-02462-1DOI Listing

Multispecies study: low-dose tributyltin impairs ovarian theca cell cholesterol homeostasis through the RXR pathway in five mammalian species including humans.

Arch Toxicol 2019 Apr 21. Epub 2019 Apr 21.

Department of Animal Science, Michigan State University, 474 S. Shaw Lane, Room 1230F, East Lansing, MI, 48824, USA.

Tributyltin (TBT), an organotin chemical used as a catalyst and biocide, can stimulate cholesterol efflux in non-steroidogenic cells. Since cholesterol is the first limiting step for sex hormone production, we hypothesized that TBT disrupts intracellular cholesterol transport and impairs steroidogenesis in ovarian theca cells. We investigated TBT's effect on cholesterol trafficking, luteinization, and steroidogenesis in theca cells of five species (human, sheep, cow, pig, and mice). Read More

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http://dx.doi.org/10.1007/s00204-019-02449-yDOI Listing

The role of fuel type and combustion phase on the toxicity of biomass smoke following inhalation exposure in mice.

Arch Toxicol 2019 Apr 20. Epub 2019 Apr 20.

Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.

The characteristics of wildland fire smoke exposures which initiate or exacerbate cardiopulmonary conditions are unclear. We previously reported that, on a mass basis, lung toxicity associated with particulate matter (PM) from flaming smoke aspirated into mouse lungs is greater than smoldering PM. In this study, we developed a computer-controlled inhalation system which can precisely control complex biomass smoke emissions from different combustion conditions. Read More

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http://dx.doi.org/10.1007/s00204-019-02450-5DOI Listing
April 2019
1 Read

A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice.

Arch Toxicol 2019 Apr 19. Epub 2019 Apr 19.

Department of Metabolic Regulation, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan.

Previous epidemiological studies have suggested a link between high-cholesterol intake and liver disease progression, including hepatocellular carcinoma (HCC). However, the precise mechanism of hepatotoxicity and hepatocarcinogenesis caused by excessive cholesterol consumption remains unclear. We aimed to investigate the impact of dietary cholesterol using hepatitis C virus core gene transgenic (HCVcpTg) mice, which spontaneously developed HCC with age. Read More

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http://dx.doi.org/10.1007/s00204-019-02440-7DOI Listing
April 2019
5.980 Impact Factor

Overcoming acquired resistance of gefitinib in lung cancer cells without T790M by AZD9291 or Twist1 knockdown in vitro and in vivo.

Arch Toxicol 2019 Apr 16. Epub 2019 Apr 16.

Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, PO Box 9190, 3302 Health Sciences Center, HSC South, 64 Medical Center Drive, Morgantown, WV, 26506, USA.

The T790M mutation is recognized as a typical mechanism of acquired resistance to first generation of epithermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib in non-small cell lung cancer (NSCLC) patients who are commonly treated by third generation of EGFR-TKI AZD9291 (osimertinib). However, the therapeutic strategy for overcoming acquired resistance to EGFR-TKIs in NSCLC patients without T790M remains to be definitively determined. In the present study, gefitinib-resistant H1650 (H1650GR) or AZD9291-resistant H1975 (H1975AR) was generated by exposing NSCLC cell line H1650 or H1975 to progressively increased concentrations of gefitinib or AZD9291 over 11 months. Read More

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http://link.springer.com/10.1007/s00204-019-02453-2
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http://dx.doi.org/10.1007/s00204-019-02453-2DOI Listing
April 2019
3 Reads

In vitro models to study insulin and glucocorticoids modulation of trimethyltin (TMT)-induced neuroinflammation and neurodegeneration, and in vivo validation in db/db mice.

Arch Toxicol 2019 Apr 16. Epub 2019 Apr 16.

Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland.

Brain susceptibility to a neurotoxic insult may be increased in a compromised health status, such as metabolic syndrome. Both metabolic syndrome and exposure to trimethyltin (TMT) are known to promote neurodegeneration. In combination the two factors may elicit additive or compensatory/regulatory mechanisms. Read More

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http://dx.doi.org/10.1007/s00204-019-02455-0DOI Listing
April 2019
1 Read

A toll-like receptor 9 agonist sensitizes mice to mitochondrial dysfunction-induced hepatic apoptosis via the Fas/FasL pathway.

Arch Toxicol 2019 Apr 16. Epub 2019 Apr 16.

Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan.

Early hepatocyte death occurs in most liver injury cases and triggers liver inflammation, which in combination with other risk factors leads to the development of liver disease. However, the pathogenesis of early phase hepatocyte death remains poorly understood. Here, C57BL/6J mice were treated with the hepatotoxic drug flucloxacillin (FLUX) and the toll-like receptor 9 agonist CpG oligodeoxynucleotide (ODN) to reproduce the early phase of drug-induced hepatotoxicity and investigate its pathogenesis. Read More

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http://dx.doi.org/10.1007/s00204-019-02454-1DOI Listing

Will worker DNELs derived under the European REACH regulation extend the landscape of occupational exposure guidance values?

Arch Toxicol 2019 Apr 16. Epub 2019 Apr 16.

Integrative Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Derived no-effect levels for workers (wDNELs) under the European REACH legislation have many aspects in common with occupational exposure limits (OELs). In an attempt to examine under which circumstances wDNELs might be used as exposure guidance outside their intended application, we compared derivation methods, coverage of substances and numerical values of wDNELs against two regulatory OEL lists (European Commission and Sweden) and three sets of recommendations (European SCOEL, German MAK and US ACGIH). Finally, we looked closer at wDNELs where SCOEL concluded that data were insufficient to derive an OEL. Read More

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http://dx.doi.org/10.1007/s00204-019-02439-0DOI Listing

1-Methoxy-3-indolylmethyl DNA adducts in six tissues, and blood protein adducts, in mice under pak choi diet: time course and persistence.

Arch Toxicol 2019 Apr 15. Epub 2019 Apr 15.

Department of Nutritional Toxicology, Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.

We previously showed that purified 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate, a secondary plant metabolite in Brassica species, is mutagenic in various in vitro systems and forms DNA and protein adducts in mouse models. In the present study, we administered 1-MIM glucosinolate in a natural matrix to mice, by feeding a diet containing pak choi powder and extract. Groups of animals were killed after 1, 2, 4 and 8 days of pak choi diet, directly or, in the case of the 8-day treatment, after 0, 8 and 16 days of recovery with pak choi-free diet. Read More

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http://dx.doi.org/10.1007/s00204-019-02452-3DOI Listing

Understanding the skin sensitization capacity of ascaridole: a combined study of chemical reactivity and activation of the innate immune system (dendritic cells) in the epidermal environment.

Arch Toxicol 2019 Apr 16. Epub 2019 Apr 16.

Dermatochemistry Laboratory, University of Strasbourg, CNRS, UMR 7177, Institut le Bel, Strasbourg, France.

To improve the prediction of the possible allergenicity of chemicals in contact with the skin, investigations of upstream events are required to better understand the molecular mechanisms involved in the initiation of allergic reactions. Ascaridole, one of the compounds responsible for skin sensitization to aged tea tree oil, degrades into intermediates that evolve via different mechanisms involving radical species. We aimed at broadening the knowledge about the contribution of radical intermediates derived from ascaridole to the skin sensitization process by assessing the reactivity profile towards amino acids, identifying whether free radicals are formed in a reconstructed human epidermis (RHE) model and their biological properties to activate the immune system, namely dendritic cells in their natural context of human HaCaT keratinocytes and RHE. Read More

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http://dx.doi.org/10.1007/s00204-019-02444-3DOI Listing
April 2019
1 Read

Toxicity of C fullerene-cisplatin nanocomplex against Lewis lung carcinoma cells.

Arch Toxicol 2019 Apr 15. Epub 2019 Apr 15.

Technical University of Applied Sciences Wildau, 1 Hochschulring Str., 15745, Wildau, Germany.

Cisplatin (Cis-Pt) is the cytotoxic agent widely used against tumors of various origin, but its therapeutic efficiency is substantially limited by a non-selective effect and high toxicity. Conjugation of Cis-Pt with nanocarriers is thought to be one option to enable drug targeting. The aim of this study was to estimate toxic effects of the nanocomplex formed by noncovalent interaction of C fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug. Read More

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http://link.springer.com/10.1007/s00204-019-02441-6
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http://dx.doi.org/10.1007/s00204-019-02441-6DOI Listing
April 2019
2 Reads

Toxicological assessment of magnesium oxide nanoparticles in HT29 intestinal cells.

Arch Toxicol 2019 Apr 15. Epub 2019 Apr 15.

Department of Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.

Nanoparticles (NPs) are increasingly used in different consumer-related areas, for instance in food packaging or as additives, because of their enormous potential. Magnesium oxide (MgO) is an EU-approved food additive (E number 530). It is commonly used as a drying agent for powdered foods, for colour retention or as a food supplement. Read More

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http://dx.doi.org/10.1007/s00204-019-02451-4DOI Listing

Pregnane X receptor mediates steatotic effects of propiconazole and tebuconazole in human liver cell lines.

Arch Toxicol 2019 Apr 15. Epub 2019 Apr 15.

Department Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.

Triazoles are commonly used fungicides which show liver toxicity in rodent studies. While hepatocellular hypertrophy is the most prominent finding, some triazoles have also been reported to cause hepatocellular steatosis. The aim of our study was to elucidate molecular mechanisms of triazole-mediated steatosis. Read More

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http://link.springer.com/10.1007/s00204-019-02445-2
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http://dx.doi.org/10.1007/s00204-019-02445-2DOI Listing
April 2019
5 Reads

The LRP6 functional mutation rs2302685 contributes to individual susceptibility to alcoholic liver injury related to the Wnt/β-catenin-TCF1-CYP2E1 signaling pathway.

Arch Toxicol 2019 Apr 11. Epub 2019 Apr 11.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Low-density lipoprotein receptor-related protein 6 (LRP6) is an important coreceptor in the Wnt/β-catenin upstream signaling pathway. Rs2302685 is a common functional mutation of LRP6 that has been previously associated with reduced alcoholic liver injury among alcoholic liver disease (ALD) patients, and the present research was designed to study the underlying mechanisms of that finding. A total of 107 ALD patients and 138 non-ALD patients were recruited from hospitalized alcoholics in China. Read More

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http://dx.doi.org/10.1007/s00204-019-02447-0DOI Listing
April 2019
5.980 Impact Factor

Quinone-thioether metabolites of hydroquinone play a dual role in promoting a vicious cycle of ROS generation: in vitro and in silico insights.

Arch Toxicol 2019 Apr 11. Epub 2019 Apr 11.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.

Humans are exposed to hydroquinone (HQ) via diet, smoking, occupation, and even via inhalation of polluted air. Given its preferential distribution in kidney and liver, the impact of biotransformation on the nephrotoxicity and hepatotoxicity of HQ was evaluated. Indeed, HQ and its metabolites, benzoquinone, and quinone-thioethers (50, 100, 200, and 400 μM) all induced ROS-dependent cell death in both HK-2, a human kidney proximal epithelial cell line, and THLE-2, a human liver epithelial cell line, in a concentration-dependent manner. Read More

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http://link.springer.com/10.1007/s00204-019-02443-4
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http://dx.doi.org/10.1007/s00204-019-02443-4DOI Listing
April 2019
2 Reads

Mechanisms and in vitro models of drug-induced cholestasis.

Arch Toxicol 2019 Apr 10. Epub 2019 Apr 10.

Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.

Cholestasis underlies one of the major manifestations of drug-induced liver injury. Drug-induced cholestatic liver toxicity is a complex process, as it can be triggered by a variety of factors that induce 2 types of biological responses, namely a deteriorative response, caused by bile acid accumulation, and an adaptive response, aimed at removing the accumulated bile acids. Several key events in both types of responses have been characterized in the past few years. Read More

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http://link.springer.com/10.1007/s00204-019-02437-2
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http://dx.doi.org/10.1007/s00204-019-02437-2DOI Listing
April 2019
13 Reads

Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment.

Arch Toxicol 2019 Apr 8. Epub 2019 Apr 8.

Johns Hopkins University School of Nursing, 525 North Wolfe Street, Baltimore, MD, 21205, USA.

Individuals treated for multidrug-resistant tuberculosis (MDR-TB) with aminoglycosides (AGs) in resource-limited settings often experience permanent hearing loss. However, AG ototoxicity has never been conceptually integrated or causally linked to MDR-TB patients' pre-treatment health condition. We sought to develop a framework that examines the relationships between pre-treatment conditions and AG-induced hearing loss among MDR-TB-infected individuals in sub-Saharan Africa. Read More

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http://link.springer.com/10.1007/s00204-019-02407-8
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http://dx.doi.org/10.1007/s00204-019-02407-8DOI Listing
April 2019
12 Reads

Report from the BfR expert hearing on practicability of hormonal measurements: recommendations for experimental design of toxicological studies with integrated hormonal end points.

Arch Toxicol 2019 Mar 30. Epub 2019 Mar 30.

German Federal Institute for Risk Assessment, Berlin, Germany.

This publication summarizes discussions that were held during an international expert hearing organized by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany, in October 2017. The expert hearing was dedicated to providing practical guidance for the measurement of circulating hormones in regulatory toxicology studies. Adequate measurements of circulating hormones have become more important given the regulatory requirement to assess the potential for endocrine disrupting properties for all substances covered by the plant protection products and biocidal products regulations in the European Union (EU). Read More

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http://dx.doi.org/10.1007/s00204-019-02436-3DOI Listing
March 2019
2 Reads

Adductomics: a promising tool for the verification of chemical warfare agents' exposures in biological samples.

Arch Toxicol 2019 Mar 28. Epub 2019 Mar 28.

Vertox Biochemistry Division, DRDE, Gwalior, India.

Humans are constantly exposed to a wide range of reactive and toxic chemicals from the different sources in everyday life. Identification of the exposed chemical helps in the detection and understanding the exposure associated adverse health effects. Covalent adducts of proteins and DNA formed after xenobiotics exposure may serve as readily measurable indicators of these exposures. Read More

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http://dx.doi.org/10.1007/s00204-019-02435-4DOI Listing
March 2019
5.980 Impact Factor

Nephrotoxicity instead of immunotoxicity of OTA is induced through DNMT1-dependent activation of JAK2/STAT3 signaling pathway by targeting SOCS3.

Arch Toxicol 2019 Mar 28. Epub 2019 Mar 28.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.

Ochratoxin A (OTA) is reported to induce nephrotoxicity and immunotoxicity in animals and humans. However, the underlying mechanism and the effects of OTA on DNA damage have not been reported until now. The present study aims to investigate OTA-induced cytotoxicity and DNA damage and the underlying mechanism in PK15 cells and PAMs. Read More

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http://dx.doi.org/10.1007/s00204-019-02434-5DOI Listing

Integrated in vitro models for hepatic safety and metabolism: evaluation of a human Liver-Chip and liver spheroid.

Arch Toxicol 2019 Mar 26. Epub 2019 Mar 26.

Drug Safety and Metabolism, AstraZeneca IMED Biotech Unit, Cambridge, CB4 0WG, UK.

Drug-induced liver injury remains a frequent reason for drug withdrawal. Accordingly, more predictive and translational models are required to assess human hepatotoxicity risk. This study presents a comprehensive evaluation of two promising models to assess mechanistic hepatotoxicity, microengineered Organ-Chips and 3D hepatic spheroids, which have enhanced liver phenotype, metabolic activity and stability in culture not attainable with conventional 2D models. Read More

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http://dx.doi.org/10.1007/s00204-019-02427-4DOI Listing
March 2019
1 Read

Ochratoxin A causes mitochondrial dysfunction, apoptotic and autophagic cell death and also induces mitochondrial biogenesis in human gastric epithelium cells.

Arch Toxicol 2019 Mar 22. Epub 2019 Mar 22.

State Key Laboratory of Silkworm Biology, Southwest University, No. 2, Tiansheng Road, Beibei District, Chongqing City, People's Republic of China.

Ochratoxin A (OTA) is a common natural contaminant found in human and animal food worldwide. Our previous work has shown that OTA can cause oxidative DNA damage, G arrest and malignant transformation of human gastric epithelium (GES-1) cells. Mitochondria are considered to be target for the action of many cytotoxic agents. Read More

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http://dx.doi.org/10.1007/s00204-019-02433-6DOI Listing
March 2019
1 Read
5.980 Impact Factor

An effective antidotal combination of polymyxin B and methylprednisolone for α-amanitin intoxication.

Arch Toxicol 2019 Mar 19. Epub 2019 Mar 19.

Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, UCIBIO, REQUIMTE, University of Porto, Rua José Viterbo Ferreira no 228, 4050-313, Porto, Portugal.

Amanita phalloides is one of the most toxic mushrooms worldwide, and it is involved in the majority of human fatal cases of mushroom poisoning. α-Amanitin, the most deleterious toxin of A. phalloides to humans, inhibits RNA polymerase II (RNAPII), causing hepatic and renal failure. Read More

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http://dx.doi.org/10.1007/s00204-019-02426-5DOI Listing
March 2019
1 Read

New insight in beryllium toxicity excluding exposure to beryllium-containing dust: accumulation patterns, target organs, and elimination.

Arch Toxicol 2019 Mar 19. Epub 2019 Mar 19.

Department of Chemistry, Ghent University, Krijgslaan 281, Ghent, 9000, Belgium.

There is much contradiction between different experimental studies on beryllium (Be) toxicity. The majority of studies focus on occupational pathologies, caused by the exposure to Be dust. However, Be pollution may affect wide population groups through other exposure routes. Read More

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http://dx.doi.org/10.1007/s00204-019-02432-7DOI Listing
March 2019
6 Reads

Interactions of human butyrylcholinesterase with phenylvalerate and acetylthiocholine as substrates and inhibitors: kinetic and molecular modeling approaches.

Arch Toxicol 2019 Mar 15. Epub 2019 Mar 15.

Institute of Bioengineering, University Miguel Hernández, Elche, Alicante, Spain.

Phenyl valerate (PV) is a substrate for measuring the PVase activity of neuropathy target esterase (NTE), a key molecular event of organophosphorus-induced delayed neuropathy. A protein with PVase activity in chicken (model for delayed neurotoxicity) was identified as butyrylcholinesterase (BChE). Purified human butyrylcholinesterase (hBChE) showed PVase activity with a similar sensitivity to inhibitors as its cholinesterase (ChE) activity. Read More

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http://dx.doi.org/10.1007/s00204-019-02423-8DOI Listing
March 2019
1 Read

Identification of anticancer OATP2B1 substrates by an in vitro triple-fluorescence-based cytotoxicity screen.

Arch Toxicol 2019 Mar 12. Epub 2019 Mar 12.

Institute of Enzymology, Research Centre for National Sciences, HAS, Budapest, 1117, Hungary.

Membrane transporters play an important role in the absorption, distribution, metabolism and excretion of drugs. The cellular accumulation of many drugs is the result of the net function of efflux and influx transporters. Efflux transporters such as P-glycoprotein/ABCB1 have been shown to confer multidrug resistance in cancer. Read More

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http://dx.doi.org/10.1007/s00204-019-02417-6DOI Listing
March 2019
1 Read

A murine ex vivo 3D kidney proximal tubule model predicts clinical drug-induced nephrotoxicity.

Arch Toxicol 2019 Mar 12. Epub 2019 Mar 12.

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA.

Drug attrition and clinical product withdrawals due to nephrotoxicity remain major challenges for pharmaceutical drug development pipelines. Currently, no reliable high-throughput in vitro screening models are available that provide reliable, predictive toxicology data for clinical nephrotoxicity. Drug screens to predict toxicity and pharmacology assessments are compromised by standard two-dimensional (2D) cell monoculture models. Read More

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http://dx.doi.org/10.1007/s00204-019-02430-9DOI Listing

Transplacental exposure to carcinogens and risks to children: evidence from biomarker studies and the utility of omic profiling.

Arch Toxicol 2019 Mar 11. Epub 2019 Mar 11.

Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635, Athens, Greece.

The factors underlying the increasing rates and the geographic variation of childhood cancers are largely unknown. Epidemiological studies provide limited evidence for a possible role in the etiology of certain types of childhood cancer of the exposure of pregnant women to environmental carcinogens (e.g. Read More

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http://dx.doi.org/10.1007/s00204-019-02428-3DOI Listing
March 2019
1 Read

Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells.

Arch Toxicol 2019 Mar 11. Epub 2019 Mar 11.

CNRS, Centrale Marseille, iSm2, UMR 7313, Aix Marseille University, 13397, Marseille, France.

Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Read More

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http://link.springer.com/10.1007/s00204-019-02425-6
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http://dx.doi.org/10.1007/s00204-019-02425-6DOI Listing
March 2019
1 Read

NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis.

Arch Toxicol 2019 Mar 8. Epub 2019 Mar 8.

Department of Pharmacology, College of Medicine, Hanyang University, Sungdong-Gu, Haengdang-Dong 17, Seoul, 133-79, Republic of Korea.

Autophagy and apoptosis are the major types of cell death in pesticide-induced neurotoxicity, and autophagy is known to play a role in cell protection by inhibiting apoptosis. In this study, we characterized the relationship between autophagy and apoptosis in diquat (DQ)-induced cell death and explored a novel pharmacotherapeutic approach involving autophagy regulation to prevent DQ neurotoxicity. DQ was cytotoxic to PC12 cells in a concentration-dependent manner, as shown by decreased cell viability and decreased dopamine (DA) levels. Read More

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http://dx.doi.org/10.1007/s00204-019-02424-7DOI Listing
March 2019
1 Read

Carbon nanotubes and crystalline silica stimulate robust ROS production, inflammasome activation, and IL-1β secretion in macrophages to induce myofibroblast transformation.

Arch Toxicol 2019 Mar 7. Epub 2019 Mar 7.

Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, 26505, USA.

Pulmonary exposure to inhaled particulates elicits complex inflammatory and fibrotic responses that may progress to chronic fibrosis. The fibrogenic potentials of respirable particulates are influenced by their physicochemical properties and their interactions with major pathways to drive fibrotic development in the lung. Macrophages were exposed to six carbon nanotubes (CNTs) of varying dimensions, crystalline silica, or carbon black (CB), with lipopolysaccharide (LPS) and transforming growth factor (TGF)-β1 as positive controls. Read More

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http://dx.doi.org/10.1007/s00204-019-02411-yDOI Listing

The protein corona suppresses the cytotoxic and pro-inflammatory response in lung epithelial cells and macrophages upon exposure to nanosilica.

Arch Toxicol 2019 Mar 5. Epub 2019 Mar 5.

Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von- Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.

Engineered amorphous silica nanoparticles (nanosilica) are one of the most abundant nanomaterials and are widely used in industry. Furthermore, novel nanosilica materials are promising theranostic tools for biomedicine. However, hazardous effects of nanosilica especially after inhalation into the lung have been documented. Read More

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http://dx.doi.org/10.1007/s00204-019-02422-9DOI Listing
March 2019
5 Reads

Bisphenol A alteration of type 1 diabetes in non-obese diabetic (NOD) female mice is dependent on window of exposure.

Arch Toxicol 2019 Mar 2. Epub 2019 Mar 2.

Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602-7382, USA.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic β-cell destruction can be mediated by dysbiosis, infiltration of pro-inflammatory immune cells, and cytokines/chemokines. Exposure to bisphenol A (BPA), an endocrine disruptor (ED), can lead to aberrant immunity and gut microbiota. We determined whether BPA had age-dependent effects on T1D by modulating immune homeostasis following various windows of exposure in non-obese diabetic (NOD) mice. Read More

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http://dx.doi.org/10.1007/s00204-019-02419-4DOI Listing
March 2019
1 Read

Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity.

Arch Toxicol 2019 Feb 27. Epub 2019 Feb 27.

Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.

We recently reported that doxorubicin decreased the expression of calpain-1/2, while inhibition of calpain activity promoted doxorubicin-induced cardiac injury in mice. In this study, we investigated whether and how elevation of calpain-2 could affect doxorubicin-triggered cardiac injury. Transgenic mice with inducible cardiomyocyte-specific expression of calpain-2 were generated. Read More

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http://link.springer.com/10.1007/s00204-019-02405-w
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http://dx.doi.org/10.1007/s00204-019-02405-wDOI Listing
February 2019
4 Reads
5.980 Impact Factor

The THP-1 cell toolbox: a new concept integrating the key events of skin sensitization.

Arch Toxicol 2019 Feb 26. Epub 2019 Feb 26.

UMR996-Inflammation, Chemokines and Immunopathology, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296, Châtenay-Malabry, France.

According to the current scientific consensus, one in vitro test is insufficient to cover the key events (KE) defined by the adverse outcome pathway (AOP) for skin sensitization. To address this issue we combined different end points in the same cell line to cover all KEs defined by the skin sensitization AOP. Since dendritic cells (DC) play a key role in the sensitization phase leading to the development of allergic contact dermatitis (ACD), we used THP-1 cells as a surrogate for DC. Read More

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http://dx.doi.org/10.1007/s00204-019-02416-7DOI Listing
February 2019
6 Reads

Transfer learning for predicting human skin sensitizers.

Arch Toxicol 2019 Feb 26. Epub 2019 Feb 26.

School of Pharmacy, Kaohsiung Medical University, 100 Shihchuan 1st Rd., Kaohsiung, 80708, Taiwan.

Computational prioritization of chemicals for potential skin sensitization risks plays essential roles in the risk assessment of environmental chemicals and drug development. Given the huge number of chemicals for testing, computational methods enable the fast identification of high-risk chemicals for experimental validation and design of safer alternatives. However, the development of robust prediction model requires a large dataset of tested chemicals that is usually not available for most toxicological endpoints, especially for human data. Read More

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http://dx.doi.org/10.1007/s00204-019-02420-xDOI Listing
February 2019
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Particulate matter 2.5 induced arrhythmogenesis mediated by TRPC3 in human induced pluripotent stem cell-derived cardiomyocytes.

Arch Toxicol 2019 Feb 26. Epub 2019 Feb 26.

Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Particulate matter (PM) is one of the most important environmental issues worldwide, which is associated with not only pulmonary but also cardiovascular diseases. However, the underlying biological mechanisms of PM related cardiovascular dysfunction remained poorly defined, especially mediated by the pathway of direct impact on vascular and heart. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide an ideal platform for studying PM-exposed cellular diseases model in vitro. Read More

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http://link.springer.com/10.1007/s00204-019-02403-y
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http://dx.doi.org/10.1007/s00204-019-02403-yDOI Listing
February 2019
2 Reads

Inhibition of thymocyte autophagy-associated CD4T thymopoiesis is involved in asthma susceptibility in mice exposed to caffeine prenatally.

Arch Toxicol 2019 Feb 25. Epub 2019 Feb 25.

Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 185, East Lake Road, Wuhan, 430071, China.

Our previous studies demonstrated that prenatal caffeine exposure (PCE) caused thymopoiesis inhibition, immune disorders, and airway remodeling in offspring, which raises the question of whether PCE is a risk factor for postnatal asthma. Meanwhile, the mechanism of PCE-induced thymopoiesis inhibition is not clear yet. Considering caffeine's pro-autophagy effects (lacking evidence in thymus) and the important role of autophagy in maintaining thymopoiesis, this study aimed to investigate whether PCE contributes to asthma susceptibility, and further explore the molecular mechanisms of thymopoiesis inhibition from the perspective of pro-autophagy effects of caffeine both in vivo and in vitro. Read More

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http://dx.doi.org/10.1007/s00204-019-02418-5DOI Listing
February 2019
1 Read

Cell-cell contacts protect against t-BuOOH-induced cellular damage and ferroptosis in vitro.

Arch Toxicol 2019 Feb 23. Epub 2019 Feb 23.

Institute of Toxicology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacherstr. 67, 55131, Mainz, Germany.

Ferroptosis is a recently discovered pathway of regulated necrosis dependent on iron and lipid peroxidation. It has gained broad attention since it is a promising approach to overcome resistance to apoptosis in cancer chemotherapy. We have recently identified tertiary-butyl hydroperoxide (t-BuOOH) as a novel inducer of ferroptosis. Read More

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http://dx.doi.org/10.1007/s00204-019-02413-wDOI Listing
February 2019
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Sirtuin-1 ameliorates cadmium-induced endoplasmic reticulum stress and pyroptosis through XBP-1s deacetylation in human renal tubular epithelial cells.

Arch Toxicol 2019 Feb 22. Epub 2019 Feb 22.

School of Public Health, Fudan University, 130 Dong'An Road, P.O. Box 288, Shanghai, 200032, China.

Cadmium (Cd), an occupational and environmental pollutant, induces nephrotoxicity by primarily damaging renal proximal tubular cells. In this study, we hypothesized that pyroptosis, a caspase-1-dependent inflammatory programmed cell death mechanism, mediates Cd-induced nephrotoxicity. Human proximal tubular epithelial HK-2 cells were treated with 0-10 µM CdCl for 48 h. Read More

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http://dx.doi.org/10.1007/s00204-019-02415-8DOI Listing
February 2019
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Significance of AHR nuclear translocation sequence in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cPLAα activation and hydronephrosis.

Arch Toxicol 2019 Feb 21. Epub 2019 Feb 21.

Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.

The aryl hydrocarbon receptor (AHR) plays a major role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced toxicity phenotypes. TCDD bound to AHR elicits both genomic action in which target genes are transcriptionally upregulated and nongenomic action in which cytosolic phospholipase Aα (cPLAα) is rapidly activated. However, how either of these actions, separately or in combination, induces toxicity phenotypes is largely unknown. Read More

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http://dx.doi.org/10.1007/s00204-019-02414-9DOI Listing
February 2019

Quantitative comparison of in vitro genotoxicity between metabolically competent HepaRG cells and HepG2 cells using the high-throughput high-content CometChip assay.

Arch Toxicol 2019 Feb 21. Epub 2019 Feb 21.

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR, 72079, USA.

In vitro genotoxicity testing that employs metabolically active human cells may be better suited for evaluating human in vivo genotoxicity than current bacterial or non-metabolically active mammalian cell systems. In the current study, 28 compounds, known to have different genotoxicity and carcinogenicity modes of action (MoAs), were evaluated over a wide range of concentrations for the ability to induce DNA damage in human HepG2 and HepaRG cells. DNA damage dose-responses in both cell lines were quantified using a combination of high-throughput high-content (HTHC) CometChip technology and benchmark dose (BMD) quantitative approaches. Read More

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http://dx.doi.org/10.1007/s00204-019-02406-9DOI Listing
February 2019
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Biomonitoring of nutritional acrylamide intake by consumers without dietary preferences as compared to vegans.

Arch Toxicol 2019 Feb 20. Epub 2019 Feb 20.

Division of Food Chemistry and Toxicology, Department of Chemistry, Technische Universitaet Kaiserslautern, Erwin-Schroedinger-Straße 52, 67663, Kaiserslautern, Germany.

Acrylamide (AA) is a heat-induced food contaminant considered as genotoxic carcinogen. The present study investigated the influence of nutritional and lifestyle preferences on human AA exposure. A 10-day human study was performed with ten volunteers without nutritional preferences (omnivores) and ten vegans. Read More

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http://dx.doi.org/10.1007/s00204-019-02412-xDOI Listing
February 2019
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Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration.

Arch Toxicol 2019 Feb 18. Epub 2019 Feb 18.

Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, 1428, Buenos Aires, Argentina.

Age-related macular degeneration (AMD) is a multifactorial retinal disease characterized by a progressive loss of central vision. Retinal pigment epithelium (RPE) degeneration is a critical event in AMD. It has been associated to A2E accumulation, which sensitizes RPE to blue light photodamage. Read More

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http://dx.doi.org/10.1007/s00204-019-02409-6DOI Listing
February 2019
2 Reads

Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats.

Arch Toxicol 2019 Feb 13. Epub 2019 Feb 13.

Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Potassium octatitanate (KO·8TiO, POT) fibers are used as an alternative to asbestos. Their shape and biopersistence suggest that they are possibly carcinogenic. However, inhalation studies have shown that respired POT fibers have little carcinogenic potential. Read More

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http://dx.doi.org/10.1007/s00204-019-02410-zDOI Listing
February 2019
5 Reads

Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

Arch Toxicol 2019 Feb 12. Epub 2019 Feb 12.

Institute for Biosafety in Plant Biotechnology, Julius Kühn-Institut (JKI), Federal Research Centre for Cultivated Plants, Erwin-Baur-Str. 27, 06484, Quedlinburg, Germany.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Read More

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http://dx.doi.org/10.1007/s00204-019-02400-1DOI Listing
February 2019
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Urinary metabolites of the UV filter octocrylene in humans as biomarkers of exposure.

Arch Toxicol 2019 Feb 9. Epub 2019 Feb 9.

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.

Octocrylene (OC) is a UV filter used in sun screens and other personal care products, but also in polymers and food contact materials for stabilization. In this study, we investigate human OC metabolism and urinary excretion after oral dosage of approx. 5 mg OC [≙ 61. Read More

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http://dx.doi.org/10.1007/s00204-019-02408-7DOI Listing
February 2019
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5.980 Impact Factor

Silica-coated magnetic nanoparticles induce glucose metabolic dysfunction in vitro via the generation of reactive oxygen species.

Arch Toxicol 2019 Feb 8. Epub 2019 Feb 8.

Department of Physiology, Department of Biomedical Sciences, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, 16499, Suwon, Republic of Korea.

Nanoparticles are a useful material in biomedicine given their unique properties and biocompatibility; however, there is increasing concern regarding the potential toxicity of nanoparticles with respect to cell metabolism. Some evidence suggests that nanoparticles can disrupt glucose and energy homeostasis. In this study, we investigated the metabolomic, transcriptomic, and integrated effects of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO(RITC)] on glucose metabolism in human embryonic kidney 293 (HEK293) cells. Read More

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http://dx.doi.org/10.1007/s00204-019-02402-zDOI Listing
February 2019
2 Reads

Repetitive antidotal treatment is crucial in eliminating eye pathology, respiratory toxicity and death following whole-body VX vapor exposure in freely moving rats.

Arch Toxicol 2019 Feb 7. Epub 2019 Feb 7.

Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, 74100, Ness Ziona, Israel.

Exposure to the chemical warfare nerve agent VX is extremely toxic, causing severe cholinergic symptoms. If not appropriately treated, death ultimately ensues. Based on our previously described whole-body vapor exposure system, we characterized in detail the clinical outcome, including respiratory dynamics, typical of whole-body exposure to lethal doses of VX vapor in freely moving rats. Read More

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http://dx.doi.org/10.1007/s00204-019-02401-0DOI Listing
February 2019
1 Read