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Archives of Toxicology

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https://www.readbyqxmd.com/read/29926130/highlight-report-false-positives-in-genotoxicity-testing
#1
EDITORIAL
Regina Stöber
No abstract text is available yet for this article.
June 20, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29916052/correction-to-polymyxin-b-causes-dna-damage-in-hk-2-cells-and-mice
#2
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
In the original publication of the article, part of Fig. 6 is missing. The missing subpanels, Fig. 6c, d are given below.
June 18, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29916051/xenobiotica-metabolizing-enzymes-in-the-skin-of-rat-mouse-pig-guinea-pig-man-and-in-human-skin-models
#3
REVIEW
F Oesch, E Fabian, Robert Landsiedel
Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial...
June 18, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29916050/opioid-analgesic-drugs-and-serotonin-toxicity-syndrome-mechanisms-animal-models-and-links-to-clinical-effects
#4
REVIEW
Brian A Baldo
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-norepinephrine reuptake inhibitors, and tricyclic antidepressants...
June 18, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29876591/autophagy-and-acetaminophen-induced-hepatotoxicity
#5
REVIEW
Shulin Shan, Zhenyu Shen, Fuyong Song
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...
June 6, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29869127/aged-rats-are-more-vulnerable-than-adolescents-to-ecstasy-induced-toxicity
#6
R Feio-Azevedo, V M Costa, D J Barbosa, A Teixeira-Gomes, I Pita, S Gomes, F C Pereira, M Duarte-Araújo, J A Duarte, F Marques, E Fernandes, M L Bastos, F Carvalho, J P Capela
3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected...
June 4, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29860548/comparison-of-iohexol-and-iodixanol-induced-nephrotoxicity-mitochondrial-damage-and-mitophagy-in-a-new-contrast-induced-acute-kidney-injury-rat-model
#7
Wei Cheng, Fei Zhao, Cheng-Yuan Tang, Xu-Wei Li, Min Luo, Shao-Bin Duan
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...
June 2, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29855658/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
#8
Jana Tulinská, Karine Adel-Patient, Hervé Bernard, Aurélia Líšková, Miroslava Kuricová, Silvia Ilavská, Mira Horváthová, Anton Kebis, Eva Rollerová, Júlia Babincová, Radka Aláčová, Jean-Michel Wal, Kerstin Schmidt, Jörg Schmidtke, Paul Schmidt, Christian Kohl, Ralf Wilhelm, Joachim Schiemann, Pablo Steinberg
The genetically modified maize event MON810 expresses a Bacillus thuringiensis-derived gene, which encodes the insecticidal protein Cry1Ab to control some lepidopteran insect pests such as the European corn borer. It has been claimed that the immune system may be affected following the oral/intragastric administration of the MON810 maize in various different animal species. In the frame of the EU-funded project GRACE, two 90-day feeding trials, the so-called studies D and E, were performed to analyze the humoral and cellular immune responses of male and female Wistar Han RCC rats fed the MON810 maize...
May 31, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29846769/ethanol-addictively-enhances-the-in-vitro-cardiotoxicity-of-cocaine-through-oxidative-damage-energetic-deregulation-and-apoptosis
#9
Maria João Martins, Rita Roque Bravo, Maria Enea, Helena Carmo, Félix Carvalho, Maria de Lourdes Bastos, Ricardo Jorge Dinis-Oliveira, Diana Dias da Silva
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 combined with EtOH...
May 30, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29845424/the-histone-deacetylases-hdac1-and-hdac2-are-required-for-the-growth-and-survival-of-renal-carcinoma-cells
#10
Nicole Kiweler, Boris Brill, Matthias Wirth, Ines Breuksch, Teresa Laguna, Cornelia Dietrich, Susanne Strand, Günter Schneider, Bernd Groner, Falk Butter, Thorsten Heinzel, Walburgis Brenner, Oliver H Krämer
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...
May 29, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29808285/galunisertib-modifies-the-liver-fibrotic-composition-in-the-abcb4ko-mouse-model
#11
Seddik Hammad, Elisabetta Cavalcanti, Julia Werle, Maria Lucia Caruso, Anne Dropmann, Antonia Ignazzi, Matthias Philip Ebert, Steven Dooley, Gianluigi Giannelli
Transforming growth factor (TGF)-β stimulates extracellular matrix (ECM) deposition during development of liver fibrosis and cirrhosis, the most important risk factor for the onset of hepatocellular carcinoma. In liver cancer, TGF-β is responsible for a more aggressive and invasive phenotype, orchestrating remodeling of the tumor microenvironment and triggering epithelial-mesenchymal transition of cancer cells. This is the scientific rationale for targeting the TGF-β pathway via a small molecule, galunisertib (intracellular inhibitor of ALK5) in clinical trials to treat liver cancer patients at an advanced disease stage...
May 28, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29804187/chronic-ingestion-of-deoxynivalenol-at-human-dietary-levels-impairs-intestinal-homeostasis-and-gut-microbiota-in-mice
#12
Cécile Vignal, Madjid Djouina, Muriel Pichavant, Ségolène Caboche, Christophe Waxin, Delphine Beury, David Hot, Corinne Gower-Rousseau, Mathilde Body-Malapel
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...
May 26, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29799070/revisiting-the-stress-paradigm-for-silica-nanoparticles-decoupling-of-the-anti-oxidative-defense-pro-inflammatory-response-and-cytotoxicity
#13
Susanne Fritsch-Decker, Clarissa Marquardt, Tobias Stoeger, Silvia Diabaté, Carsten Weiss
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 in response to nanosilica at max...
May 24, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29796692/the-impact-of-desorption-kinetics-from-albumin-on-hepatic-extraction-efficiency-and-hepatic-clearance-a-model-study
#14
Sophia Krause, Kai-Uwe Goss
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...
May 23, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29785638/intermittent-convection-enhanced-delivery-of-gdnf-into-rhesus-monkey-putamen-absence-of-local-or-cerebellar-toxicity
#15
Matthias Luz, Philip C Allen, John Bringas, Chris Boiko, Diane E Stockinger, Kristen J Nikula, Owen Lewis, Max Woolley, H Christian Fibiger, Krystof Bankiewicz, Erich Mohr
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 lesions...
May 22, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29785637/frzb1-rs2242070-polymorphisms-is-associated-with-brick-tea-type-skeletal-fluorosis-in-kazakhs-but-not-in-tibetans-china
#16
Yanmei Yang, Qiaoshi Zhao, Yang Liu, Xiaona Liu, Yanru Chu, Huazhu Yan, Yumei Fan, Simeng Huo, Limei Wang, Qun Lou, Ning Guo, Dianjun Sun, Yanhui Gao
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 fluorosis risk in a cross-sectional case-control study conducted in Sinkiang and Qinghai, China...
May 21, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29779177/computational-identification-of-structural-factors-affecting-the-mutagenic-potential-of-aromatic-amines-study-design-and-experimental-validation
#17
Svetoslav H Slavov, Iva Stoyanova-Slavova, William Mattes, Richard D Beger, Beat J Brüschweiler
A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13 C and 15 N 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 (OECD 2004) compliant models...
May 19, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29774371/prediction-of-deoxynivalenol-toxicokinetics-in-humans-by-in-vitro-to-in-vivo-extrapolation-and-allometric-scaling-of-in-vivo-animal-data
#18
Christiane Kruse Fæste, Lada Ivanova, Amin Sayyari, Ulrik Hansen, Tore Sivertsen, Silvio Uhlig
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 allometric scaling of reported in vivo animal parameters to predict the plasma clearance [0...
May 17, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29766219/association-study-of-genetic-variants-in-estrogen-metabolic-pathway-genes-and-colorectal-cancer-risk-and-survival
#19
Shuwei Li, Lisheng Xie, Mulong Du, Kaili Xu, Lingjun Zhu, Haiyan Chu, Jinfei Chen, Meilin Wang, Zhengdong Zhang, Dongying Gu
Although studies have investigated the association of genetic variants and the abnormal expression of estrogen-related genes with colorectal cancer risk, the evidence remains inconsistent. We clarified the relationship of genetic variants in estrogen metabolic pathway genes with colorectal cancer risk and survival. A case-control study was performed to assess the association of single-nucleotide polymorphisms (SNPs) in ten candidate genes with colorectal cancer risk in a Chinese population. A logistic regression model and Cox regression model were used to calculate SNP effects on colorectal cancer susceptibility and survival, respectively...
May 16, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#20
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
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