Recent biomonitoring reports on phosphate ester flame retardants: a short review.
e; JP Abstract Organophosphate triesters (PEFRs) are used increasingly as flame retardants and plasticizers in a variety of applications, such as building materials, textiles, and electric and electronic equipment. They have been proposed as alternatives to brominated flame retardants. This updated review shows that biomonitoring has gained incrementally greater importance in evaluating human exposure to PEFRs, and it holds the advantage of taking into account the multiple potential sources and various intake pathways of PEFRs. Simultaneous and extensive internal exposure to a broad range of PEFRs have been report...
Source: Archives of Toxicology - August 10, 2018 Category: Toxicology Authors: Saillenfait AM, Ndaw S, Robert A, Sabaté JP Tags: Arch Toxicol Source Type: research

Chemical-induced contact allergy: from mechanistic understanding to risk prevention.
Abstract Chemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune disease, resulting in erythema and eczema. Chemical allergy is of considerable importance to the toxicologist, who has the responsibility of identifying and characterizing the allergenic potential of chemicals, and estimating the risk they pose to human health. This review aimed ...
Source: Archives of Toxicology - August 10, 2018 Category: Toxicology Authors: Corsini E, Engin AB, Neagu M, Galbiati V, Nikitovic D, Tzanakakis G, Tsatsakis AM Tags: Arch Toxicol Source Type: research

MicroRNA-942 mediates hepatic stellate cell activation by regulating BAMBI expression in human liver fibrosis.
In conclusion, the TGF-β and LPS-induced miR-942 mediates HSC activation through downregulation of BAMBI in human liver fibrosis. Our study provides new insights on the molecular mechanism of HSC activation and fibrosis. PMID: 30097701 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - August 10, 2018 Category: Toxicology Authors: Tao L, Xue D, Shen D, Ma W, Zhang J, Wang X, Zhang W, Wu L, Pan K, Yang Y, Nwosu ZC, Dooley S, Seki E, Liu C Tags: Arch Toxicol Source Type: research

Effect of acute exposure to toluene on cortical excitability, neuroplasticity, and motor learning in healthy humans.
This study encourages further research to obtain more knowledge about mechanisms of action and effects of toluene on both naïve and chronically exposed populations. PMID: 30097702 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - August 10, 2018 Category: Toxicology Authors: Yavari F, van Thriel C, Nitsche MA, Kuo MF Tags: Arch Toxicol Source Type: research

The metabolic fate of fenclozic acid in chimeric mice with a humanized liver.
Abstract The metabolic fate of the human hepatotoxin fenclozic acid ([2-(4-chlorophenyl)-1,3-thiazol-4-yl]acetic acid) (Myalex) was studied in normal and bile-cannulated chimeric mice with a humanized liver, following oral administration of 10 mg/kg. This in vivo animal model was investigated to assess its utility to study "human" metabolism of fenclozic acid, and in particular to explore the formation of electrophilic reactive metabolites (RMs), potentially unique to humans. Metabolism was extensive, particularly involving the carboxylic acid-containing side chain. Metabolism resulted in the format...
Source: Archives of Toxicology - August 9, 2018 Category: Toxicology Authors: Ekdahl A, Weidolf L, Baginski M, Morikawa Y, Thompson RA, Wilson ID Tags: Arch Toxicol Source Type: research

Correction to: 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.
r F Abstract The original article can be found online. PMID: 30088018 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - August 7, 2018 Category: Toxicology Authors: Schwartz-Zimmermann HE, Hametner C, Nagl V, Fiby I, Macheiner L, Winkler J, Dänicke S, Clark E, Pestka JJ, Berthiller F Tags: Arch Toxicol Source Type: research

Inhibition and stimulation of the human breast cancer resistance protein as in vitro predictor of drug-drug interactions of drugs of abuse.
Abstract Transporter-mediated drug-drug interactions (DDI) may induce adverse clinical events. As drugs of abuse (DOA) are marketed without preclinical safety studies, only very limited information about interplay with membrane transporters are available. Therefore, 13 DOA of various classes were tested for their in vitro affinity to the human breast cancer resistance protein (hBCRP), an important efflux transporter. As adenosine 5'-triphosphate (ATP) hydrolysis is crucial for hBCRP activity, adenosine 5'-diphosphate (ADP) formation was measured and used as in vitro marker for hBCRP ATPase activity. ADP quantifica...
Source: Archives of Toxicology - August 6, 2018 Category: Toxicology Authors: Wagmann L, Maurer HH, Meyer MR Tags: Arch Toxicol Source Type: research

Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI.
In conclusion, the present study is in agreement with the concept that pericentral CYPs form NAPQI that in the same cell binds to and depletes GSH but a lower level of GSH adducts is also observed in the periportal region. The results also provide further evidence of the recently published concept of 'aggravated loss of clearance capacity' according to which also liver tissue that survives intoxication may transiently show decreased metabolic capacity. PMID: 30039229 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 23, 2018 Category: Toxicology Authors: Sezgin S, Hassan R, Zühlke S, Kuepfer L, Hengstler JG, Spiteller M, Ghallab A Tags: Arch Toxicol Source Type: research

Opinion letter regarding the article Arch Toxicol https://doi.org/10.1007/s00204-018-2240-x.
PMID: 30039230 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 23, 2018 Category: Toxicology Authors: Brozovic A Tags: Arch Toxicol Source Type: research

Human metabolism and kinetics of tri-(2-ethylhexyl) trimellitate (TEHTM) after oral administration.
This study is the first to elucidate TEHTM metabolism pathways in humans and to identify metabolites of TEHTM in blood and urine by usage of especially designed human biomonitoring methods. Powerful tools for exposure monitoring and risk assessment of TEHTM are therewith available for future research. PMID: 30027468 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 19, 2018 Category: Toxicology Authors: Höllerer C, Becker G, Göen T, Eckert E Tags: Arch Toxicol Source Type: research

Tributyltin induces a transcriptional response without a brite adipocyte signature in adipocyte models.
This study is the first to show that an environmental PPARγ ligand has a limited capacity to induce health-promoting activities of PPARγ. PMID: 30027469 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 19, 2018 Category: Toxicology Authors: Kim S, Li A, Monti S, Schlezinger JJ Tags: Arch Toxicol Source Type: research

Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells.
In this study, lung cancer cells, A549, were employed as the model to investigate the effects of three PFAAs with different carbon chain lengths on cell autophagy. Through Western blot analysis on LC3-I/II ratio of cells exposed to non-cytotoxic concentration (200 µM) and cytotoxic concentration (350 µM), we found concentration-dependent increase of autophagosomes in cells, which was further confirmed by TEM examination on ultra-thin section of cells and fluorescence imaging on autophagosomes in live cells. The abundance of p62 increased with the PFAAs concentration indicating the blockage of autophag...
Source: Archives of Toxicology - July 18, 2018 Category: Toxicology Authors: Xin Y, Wan B, Yang Y, Cui XJ, Xie YC, Guo LH Tags: Arch Toxicol Source Type: research

Comprehensive analysis of serum microRNAs in hepatic sinusoidal obstruction syndrome (SOS) in rats: implication as early phase biomarkers for SOS.
In conclusion, we found that LSEC-derived miR-21-5p and especially miR-511-3p in serum would serve as early phase biomarkers for SOS in response to LSEC damage. PMID: 30019166 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 17, 2018 Category: Toxicology Authors: Takeuchi M, Oda S, Tsuneyama K, Yokoi T Tags: Arch Toxicol Source Type: research

Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans.
Abstract Zearalenone-14-glucoside (ZEN-14G), the modified mycotoxin of zearalenone (ZEN), has attracted considerable attention due to its high potential to be hydrolyzed into ZEN, which would exert toxicity. It has been confirmed that the microflora could metabolize ZEN-14G to ZEN. However, the metabolic profile of ZEN-14G and whether it could be deglucosidated in the liver are unknown. To thoroughly investigate the metabolism of ZEN-14G, in vitro metabolism including phase I and phase II metabolism was studied using liquid chromatography coupled to high-resolution mass spectrometry. Additionally, in vivo metaboli...
Source: Archives of Toxicology - July 17, 2018 Category: Toxicology Authors: Yang S, Zhang H, Zhang J, Li Y, Jin Y, Zhang S, De Saeger S, Li Y, Zhou J, Sun F, De Boevre M Tags: Arch Toxicol Source Type: research

Inverse agonist of ERR γ reduces cannabinoid receptor type 1-mediated induction of fibrinogen synthesis in mice with a high-fat diet-intoxicated liver.
Inverse agonist of ERRγ reduces cannabinoid receptor type 1-mediated induction of fibrinogen synthesis in mice with a high-fat diet-intoxicated liver. Arch Toxicol. 2018 Jul 17;: Authors: Zhang Y, Kim DK, Jung YS, Kim YH, Lee YS, Kim J, Jeong WI, Lee IK, Cho SJ, Dooley S, Lee CH, Choi HS Abstract Upon liver intoxication with malnutrition or high-fat diet feeding, fibrinogen is synthesized by hepatocytes and secreted into the blood in human and mouse. Its primary function is to occlude blood vessels upon damage and thereby stop excessive bleeding. High fibrinogen levels may contribute to the deve...
Source: Archives of Toxicology - July 17, 2018 Category: Toxicology Authors: Zhang Y, Kim DK, Jung YS, Kim YH, Lee YS, Kim J, Jeong WI, Lee IK, Cho SJ, Dooley S, Lee CH, Choi HS Tags: Arch Toxicol Source Type: research

Regioselective glucuronidation of daidzein in liver and intestinal microsomes of humans, monkeys, rats, and mice.
Abstract Daidzein, one of the major soy isoflavones, has a number of beneficial bioactivities for human health. It is mainly metabolized into 7- and/or 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in mammals, including humans. The present study was conducted to examine the regioselective glucuronidation of daidzein at the 7- and 4'-hydroxyl groups in the liver and intestinal microsomes of humans, monkeys, rats, and mice. Daidzein glucuronidation activities at substrate concentrations of 1.0-200 µM were assessed, and Eadie-Hofstee plots were constructed. The kinetics for 7- and 4'-glucuro...
Source: Archives of Toxicology - July 16, 2018 Category: Toxicology Authors: Hanioka N, Ohkawara S, Isobe T, Ochi S, Tanaka-Kagawa T, Jinno H Tags: Arch Toxicol Source Type: research

Correction to: Regulation of SIRT1/AMPK axis is critically involved in gallotannin-induced senescence and impaired autophagy leading to cell death in hepatocellular carcinoma cells.
This article contains an error. PMID: 30009356 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 16, 2018 Category: Toxicology Authors: Kwon HY, Kim JH, Kim B, Srivastava SK, Kim SH Tags: Arch Toxicol Source Type: research

Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq.
This study also reiterates previous findings that chemical-induced transcriptomic alterations occur prior to cytotoxicity and that transcriptomics provides in depth mechanistic information of the effects of chemicals on cellular transcriptional responses. TempO-Seq is a robust transcriptomic platform that is well suited for in vitro toxicity experiments. PMID: 30008028 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 14, 2018 Category: Toxicology Authors: Limonciel A, Ates G, Carta G, Wilmes A, Watzele M, Shepard PJ, VanSteenhouse HC, Seligmann B, Yeakley JM, van de Water B, Vinken M, Jennings P Tags: Arch Toxicol Source Type: research

Effects of antiepileptic drugs on lipogenic gene regulation and hyperlipidemia risk in Taiwan: a nationwide population-based cohort study and supporting in vitro studies.
Abstract To characterize the association between epilepsy, use of antiepileptic drugs (AEDs), and the risk of hyperlipidemia, we conducted a nationwide population-based cohort study with data obtained from the National Health Insurance Research Database of Taiwan. The effects of AEDs on lipogenic gene expression were also examined in vitro. We identified 3617 cases involving patients, whose epilepsy was newly diagnosed between 2000 and 2011, and selected a comparison cohort comprising 14,468 patients without epilepsy. The Cox proportional hazards model was used to evaluate the association between epilepsy, AED use...
Source: Archives of Toxicology - July 13, 2018 Category: Toxicology Authors: Li YW, Wang CH, Chen CJ, Wang CCN, Lin CL, Cheng WK, Shen HY, Lim YP Tags: Arch Toxicol Source Type: research

Infer the in vivo point of departure with ToxCast in vitro assay data using a robust learning approach.
Abstract The development and application of high throughput in vitro assays is an important development for risk assessment in the twenty-first century. However, there are still significant challenges to incorporate in vitro assays into routine toxicity testing practices. In this paper, a robust learning approach was developed to infer the in vivo point of departure (POD) with in vitro assay data from ToxCast and Tox21 projects. Assay data from ToxCast and Tox21 projects were utilized to derive the in vitro PODs for several hundred chemicals. These were combined with in vivo PODs from ToxRefDB regarding the rat an...
Source: Archives of Toxicology - July 11, 2018 Category: Toxicology Authors: Wang D Tags: Arch Toxicol Source Type: research

Aldo-keto reductase 1C3 (AKR1C3): a missing piece of the puzzle in the dinaciclib interaction profile.
In conclusion, our results indicate that dinaciclib may potentially increase the therapeutic efficacy and safety of anthracyclines by preventing anthracycline resistance and minimizing their adverse effects. PMID: 29992508 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 10, 2018 Category: Toxicology Authors: Novotná E, Büküm N, Hofman J, Flaxová M, Kouklíková E, Louvarová D, Wsól V Tags: Arch Toxicol Source Type: research

Genetic ablation of pannexin1 counteracts liver fibrosis in a chemical, but not in a surgical mouse model.
This study shows for the first time an etiology-dependent role for pannexin1 signaling in experimental liver fibrosis. PMID: 29987408 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 9, 2018 Category: Toxicology Authors: Crespo Yanguas S, da Silva TC, Pereira IVA, Maes M, Willebrords J, Shestopalov VI, Goes BM, Sayuri Nogueira M, Alves de Castro I, Romualdo GR, Barbisan LF, Gijbels E, Vinken M, Cogliati B Tags: Arch Toxicol Source Type: research

Stem cells are the most sensitive screening tool to identify toxicity of GATA4-targeted novel small-molecule compounds.
In this study we aimed to compare different cardiac and stem cell models for in vitro toxicity testing and to elucidate structure-toxicity relationships of novel compounds targeting the cardiac transcription factor GATA4. By screening the effects of eight compounds at concentrations ranging from 10 nM up to 30 µM on the viability of eight different cell types, we identified significant cell type- and structure-dependent toxicity profiles. We further characterized two compounds in more detail using high-content analysis. The results highlight the importance of cell type selection for toxicity screening and i...
Source: Archives of Toxicology - July 9, 2018 Category: Toxicology Authors: Karhu ST, Välimäki MJ, Jumppanen M, Kinnunen SM, Pohjolainen L, Leigh RS, Auno S, Földes G, Boije Af Gennäs G, Yli-Kauhaluoma J, Ruskoaho H, Talman V Tags: Arch Toxicol Source Type: research

The role of SerpinB2 in human bronchial epithelial cells responses to particulate matter exposure.
In conclusion, here we show that PAI-2 regulates CDH1 gene/cadherin-1 protein expression in bronchial HBEC3-KT cells, and this mechanism might be involved in the regulation of cell migration. SERPINB2 down-regulation should be considered part of EMT, and the over-expression of SERPINB2 in PM-exposed samples might be interpreted as an initial protective mechanism. PMID: 29987410 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 9, 2018 Category: Toxicology Authors: Longhin E, Camatini M, Bersaas A, Mantecca P, Mollerup S Tags: Arch Toxicol Source Type: research

Urinary biomarkers of exposure to the mycoestrogen zearalenone and its modified forms in German adults.
In conclusion, biomonitoring can help to assess consumer exposure to the estrogenic mycotoxin ZEN and its modified forms and to identify persons at higher risk. PMID: 29980802 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 6, 2018 Category: Toxicology Authors: Ali N, Degen GH Tags: Arch Toxicol Source Type: research

High-throughput metabolism-induced toxicity assays demonstrated on a 384-pillar plate.
Abstract The US Environmental Protection Agency (EPA) launched the Transform Tox Testing Challenge in 2016 with the goal of developing practical methods that can be integrated into conventional high-throughput screening (HTS) assays to better predict the toxicity of parent compounds and their metabolites in vivo. In response to this need and to retrofit existing HTS assays for assessing metabolism-induced toxicity of compounds, we have developed a 384-pillar plate that is complementary to traditional 384-well plates and ideally suited for culturing human cells in three dimensions at a microscale. Briefly, human em...
Source: Archives of Toxicology - July 4, 2018 Category: Toxicology Authors: Yu KN, Kang SY, Hong S, Lee MY Tags: Arch Toxicol Source Type: research

Confounding influence of tamoxifen in mouse models of Cre recombinase-induced gene activity or modulation.
y S Abstract Tamoxifen (TAM) is commonly used for cell type specific Cre recombinase-induced gene inactivation and in cell fate tracing studies. Inducing a gene knockout by TAM and using non-TAM exposed mice as controls lead to a situation where differences are interpreted as consequences of the gene knockout but in reality result from TAM-induced changes in hepatic metabolism. The degree to which TAM may compromise the interpretation of animal experiments with inducible gene expression still has to be elucidated. Here, we report that TAM strongly attenuates CCl4-induced hepatotoxicity in male C57Bl/6N mice, even ...
Source: Archives of Toxicology - July 4, 2018 Category: Toxicology Authors: Hammad S, Othman A, Meyer C, Telfah A, Lambert J, Dewidar B, Werle J, Nwosu ZC, Mahli A, Dormann C, Gao Y, Gould K, Han M, Yuan X, Gogiashvili M, Hergenröder R, Hellerbrand C, Thomas M, Ebert MP, Amasheh S, Hengstler JG, Dooley S Tags: Arch Toxicol Source Type: research

Circadian clock pathway genes associated with colorectal cancer risk and prognosis.
Abstract Circadian clock genes influence biological processes and may be involved in tumorigenesis. We systematically evaluated genetic variants in the circadian clock pathway genes associated with colorectal cancer risk and survival. We evaluated the association of 119 single nucleotide polymorphisms (SNPs) in 27 circadian clock pathway genes with the risk of colorectal cancer in a case-control study (1150 cases and 1342 controls). The false discovery rate (FDR) method was applied to correct for multiple comparisons. Gene-based analysis was performed by the sequence kernel association test (SKAT). Cox proportiona...
Source: Archives of Toxicology - July 2, 2018 Category: Toxicology Authors: Gu D, Li S, Ben S, Du M, Chu H, Zhang Z, Wang M, Zhang ZF, Chen J Tags: Arch Toxicol Source Type: research

Highlight report: quality control of stem cell-derived hepatocytes.
va DF PMID: 29968160 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - July 2, 2018 Category: Toxicology Authors: González Leiva DF Tags: Arch Toxicol Source Type: research

Modeling of early hepatocellular carcinoma.
PMID: 29936628 [PubMed - in process] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 26, 2018 Category: Toxicology Authors: Ghallab A Tags: Arch Toxicol Source Type: research

Highlight report: hepatotoxicity prediction with Hep3B cells.
PMID: 29936629 [PubMed - in process] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 26, 2018 Category: Toxicology Authors: Hammad S, Ellethy T, Othman A, Mahmoud HYAH Tags: Arch Toxicol Source Type: research

Correction to: An evidence-based review of the genotoxic and reproductive effects of sulfur mustard.
Abstract This is with reference to the note of the Editor-in-Chief of the Archives of Toxicology. PMID: 29936630 [PubMed - in process] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 26, 2018 Category: Toxicology Authors: Khan F, Niaz K, Ismail Hassan F, Abdollahi M Tags: Arch Toxicol Source Type: research

Highlight report: False positives in genotoxicity testing.
r R PMID: 29926130 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 20, 2018 Category: Toxicology Authors: Stöber R Tags: Arch Toxicol Source Type: research

Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects.
Abstract Drugs may cause serotonin toxicity by a number of different mechanisms including inhibition of serotonin uptake and metabolism, increased serotonin synthesis and release, activation of serotonin receptors, and inhibition of cytochrome P450 oxidases. Some drug interactions involving opioids can increase intrasynaptic levels of serotonin, and opioid analgesic drugs are now recognized as being involved in some cases of serotonin toxicity especially if administered in conjunction with other serotonergic medications including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-nore...
Source: Archives of Toxicology - June 18, 2018 Category: Toxicology Authors: Baldo BA Tags: Arch Toxicol Source Type: research

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.
Conclusions section in the end of this review. PMID: 29916051 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 18, 2018 Category: Toxicology Authors: Oesch F, Fabian E, Landsiedel R Tags: Arch Toxicol Source Type: research

Correction to: Polymyxin B causes DNA damage in HK-2 cells and mice.
Abstract In the original publication of the article, part of Fig. 6 is missing. The missing subpanels, Fig. 6c, d are given below. PMID: 29916052 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 18, 2018 Category: Toxicology Authors: Yun B, Zhang T, Azad MAK, Wang J, Nowell CJ, Kalitsis P, Velkov T, Hudson DF, Li J Tags: Arch Toxicol Source Type: research

Autophagy and acetaminophen-induced hepatotoxicity.
Abstract Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. APAP overdose can induce acute liver injury in humans, which is responsible for approximately 50% of total cases of acute liver failure in the United States and some European countries. Currently, the metabolism of APAP in the body has been extensively investigated; however, the exact mechanisms for APAP hepatotoxicity are not well understood. Recent studies have shown that mitochondrial dysfunction, oxidative stress and inflammatory responses play a critical role in the pathogenesis of APAP hepatotoxicity. Autophagy is a catabolic mach...
Source: Archives of Toxicology - June 6, 2018 Category: Toxicology Authors: Shan S, Shen Z, Song F Tags: Arch Toxicol Source Type: research

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.
In conclusion, age is a determinant factor for the toxic events promoted by "ecstasy". This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following "ecstasy". PMID: 29869127 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 4, 2018 Category: Toxicology Authors: Feio-Azevedo R, Costa VM, Barbosa DJ, Teixeira-Gomes A, Pita I, Gomes S, Pereira FC, Duarte-Araújo M, Duarte JA, Marques F, Fernandes E, Bastos ML, Carvalho F, Capela JP Tags: Arch Toxicol Source Type: research

Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in a new contrast-induced acute kidney injury rat model.
Abstract Recent progress in angiography and interventional therapy has revived interest in comparison of nephrotoxicity of low-or iso-osmolar contrast media, but detailed mechanisms and effective treatments of contrast-induced acute kidney injury (CI-AKI) remain elusive. We established a new model of CI-AKI and compared the nephrotoxicity of iohexol and iodixanol with a focus on renal oxidative stress, mitochondrial damage and mitophagy. Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats. Compared with iodixanol, iohexol induced a gr...
Source: Archives of Toxicology - June 2, 2018 Category: Toxicology Authors: Cheng W, Zhao F, Tang CY, Li XW, Luo M, Duan SB Tags: Arch Toxicol Source Type: research

Humoral and cellular immune response in Wistar Han RCC rats fed two genetically modified maize MON810 varieties for 90  days (EU 7th Framework Programme project GRACE).
Humoral and cellular immune response in Wistar Han RCC rats fed two genetically modified maize MON810 varieties for 90 days (EU 7th Framework Programme project GRACE). Arch Toxicol. 2018 May 31;: Authors: Tulinská J, Adel-Patient K, Bernard H, Líšková A, Kuricová M, Ilavská S, Horváthová M, Kebis A, Rollerová E, Babincová J, Aláčová R, Wal JM, Schmidt K, Schmidtke J, Schmidt P, Kohl C, Wilhelm R, Schiemann J, Steinberg P Abstract The genetically modified maize event MON810 expresses a Bacillus thuringiensis-deriv...
Source: Archives of Toxicology - May 31, 2018 Category: Toxicology Authors: Tulinská J, Adel-Patient K, Bernard H, Líšková A, Kuricová M, Ilavská S, Horváthová M, Kebis A, Rollerová E, Babincová J, Aláčová R, Wal JM, Schmidt K, Schmidtke J, Schmidt P, Kohl C, Wilhelm R, Schiemann J, Steinberg P Tags: Arch Toxicol Source Type: research

Ethanol addictively enhances the in vitro cardiotoxicity of cocaine through oxidative damage, energetic deregulation, and apoptosis.
Abstract Cocaine (COC) is frequently consumed in polydrug abuse settings, and ethanol (EtOH) is the most prominent co-abused substance. Clinical data and experimental evidence suggest that the co-administration of COC with EtOH can be more cardiotoxic than EtOH or COC alone, but information on the molecular pathways involved is scarce. Since these data are crucial to potentiate the identification of therapeutic targets to treat intoxications, we sought to (i) elucidate the type of interaction that occurs between both substances, and (ii) assess the mechanisms implicated in the cardiotoxic effects elicited by COC c...
Source: Archives of Toxicology - May 30, 2018 Category: Toxicology Authors: Martins MJ, Roque Bravo R, Enea M, Carmo H, Carvalho F, Bastos ML, Dinis-Oliveira RJ, Dias da Silva D Tags: Arch Toxicol Source Type: research

The histone deacetylases HDAC1 and HDAC2 are required for the growth and survival of renal carcinoma cells.
OH Abstract Novel therapies are required for the treatment of metastatic renal cell carcinoma (RCC), which is associated with inoperable disease and patient death. Histone deacetylases (HDACs) are epigenetic modifiers and potential drug targets. Additional information on molecular pathways that are altered by histone deacetylase inhibitors (HDACi) in RCC cells is warranted. It should equally be delineated further which individual members of the 18 mammalian HDACs determine the survival and tumor-associated gene expression programs of such cells. Most importantly, an ongoing dispute whether HDACi promote or suppre...
Source: Archives of Toxicology - May 29, 2018 Category: Toxicology Authors: Kiweler N, Brill B, Wirth M, Breuksch I, Laguna T, Dietrich C, Strand S, Schneider G, Groner B, Butter F, Heinzel T, Brenner W, Krämer OH Tags: Arch Toxicol Source Type: research

Galunisertib modifies the liver fibrotic composition in the Abcb4Ko mouse model.
In conclusion, TGF-β inhibition by galunisertib interferes, to some extent, with chronic liver progression, not by reducing the stage of liver fibrosis as measured by different scoring systems, but rather by modulating the biochemical composition of the deposited ECM, likely affecting the fate of non-parenchymal cells. PMID: 29808285 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 28, 2018 Category: Toxicology Authors: Hammad S, Cavalcanti E, Werle J, Caruso ML, Dropmann A, Ignazzi A, Ebert MP, Dooley S, Giannelli G Tags: Arch Toxicol Source Type: research

Chronic ingestion of deoxynivalenol at human dietary levels impairs intestinal homeostasis and gut microbiota in mice.
Abstract The mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereals and their by-products in areas with a moderate climate. Produced by Fusarium species, it is one of the most prevalent mycotoxins in cereal crops worldwide, and the most frequently occurring type B trichothecene in Europe. Due to its toxic properties, high stability and prevalence, the presence of DON in the food chain could represent a major public health risk. However, despite its well-known acute toxicological effects, information on the adverse effects of realistic exposure remains limited. We orally exposed mice during 9 mont...
Source: Archives of Toxicology - May 26, 2018 Category: Toxicology Authors: Vignal C, Djouina M, Pichavant M, Caboche S, Waxin C, Beury D, Hot D, Gower-Rousseau C, Body-Malapel M Tags: Arch Toxicol Source Type: research

Revisiting the stress paradigm for silica nanoparticles: decoupling of the anti-oxidative defense, pro-inflammatory response and cytotoxicity.
iss C Abstract Engineered amorphous silica nanoparticles (nanosilica) are widely used in industry yet can induce adverse effects, which might be classified according to the oxidative stress model. However, the underlying mechanisms as well as the potential interactions of the three postulated different tiers of toxicity-i.e. oxidative-, pro-inflammatory- and cytotoxic-stress response-are poorly understood. As macrophages are primary targets of nanoparticles, we used several macrophage models, primarily murine RAW264.7 macrophages, and monitored pro-inflammatory and anti-oxidative reactions as well as cytotoxicity ...
Source: Archives of Toxicology - May 24, 2018 Category: Toxicology Authors: Fritsch-Decker S, Marquardt C, Stoeger T, Diabaté S, Weiss C Tags: Arch Toxicol Source Type: research

The impact of desorption kinetics from albumin on hepatic extraction efficiency and hepatic clearance: a model study.
Abstract Until now, the question whether slow desorption of compounds from transport proteins like the plasma protein albumin can affect hepatic uptake and thereby hepatic metabolism of these compounds has not yet been answered conclusively. This work now combines recently published experimental desorption rate constants with a liver model to address this question. For doing so, the used liver model differentiates the bound compound in blood, the unbound compound in blood and the compound within the hepatocytes as three well-stirred compartments. Our calculations show that slow desorption kinetics from albumin can...
Source: Archives of Toxicology - May 23, 2018 Category: Toxicology Authors: Krause S, Goss KU Tags: Arch Toxicol Source Type: research

Intermittent convection-enhanced delivery of GDNF into rhesus monkey putamen: absence of local or cerebellar toxicity.
Abstract Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesi...
Source: Archives of Toxicology - May 22, 2018 Category: Toxicology Authors: Luz M, Allen PC, Bringas J, Boiko C, Stockinger DE, Nikula KJ, Lewis O, Woolley M, Fibiger HC, Bankiewicz K, Mohr E Tags: Arch Toxicol Source Type: research

FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China.
Abstract Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluoros...
Source: Archives of Toxicology - May 21, 2018 Category: Toxicology Authors: Yang Y, Zhao Q, Liu Y, Liu X, Chu Y, Yan H, Fan Y, Huo S, Wang L, Lou Q, Guo N, Sun D, Gao Y Tags: Arch Toxicol Source Type: research

Computational identification of structural factors affecting the mutagenic potential of aromatic amines: study design and experimental validation.
BJ Abstract A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13C and 15N NMR chemical shifts augmented with through-space interatomic distances was used to model the mutagenicity of 554 primary and 419 secondary aromatic amines. A robust modeling strategy supported by extensive validation including randomized training/hold-out test set pairs, validation sets, "blind" external test sets as well as experimental validation was applied to avoid over-parameterization and build Organization for Economic Cooperation and Development ...
Source: Archives of Toxicology - May 19, 2018 Category: Toxicology Authors: Slavov SH, Stoyanova-Slavova I, Mattes W, Beger RD, Brüschweiler BJ Tags: Arch Toxicol Source Type: research

Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data.
ig S Abstract Deoxynivalenol (DON) is the most prevalent mycotoxin in cereals worldwide. It can cause adverse health effects in humans and animals, and maximum levels in food and feed have been implemented by food authorities based on risk assessments derived from estimated intake levels. The lack of human toxicokinetic data such as absorption, distribution, and elimination characteristics hinders the direct calculation of DON plasma levels and exposure. In the present study, we have, therefore, used in vitro-to-in vivo extrapolation of depletion constants in hepatic microsomes from different species and allometri...
Source: Archives of Toxicology - May 17, 2018 Category: Toxicology Authors: Fæste CK, Ivanova L, Sayyari A, Hansen U, Sivertsen T, Uhlig S Tags: Arch Toxicol Source Type: research