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Toxicology Letters

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https://www.readbyqxmd.com/read/29037509/structure-determination-of-disease-associated-peak-aaa-from-l-tryptophan-implicated-in-the-eosinophilia-myalgia-syndrome
#1
Klaus Klarskov, Hugo Gagnon, Pierre-Luc Boudreault, Chad Normandin, Baptiste Plancq, Eric Marsault, Gerald J Gleich, Stephen Naylor
The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of L-tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers...
October 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29030272/impact-of-fasting-followed-by-short-term-exposure-to-interleukin-6-on-cytochrome-p450-mrna-in-mice
#2
Martin Krøyer Rasmussen, Lærke Bertholdt, Anders Gudiksen, Henriette Pilegaard, Jakob G Knudsen
mRNA expression of the cytochrome P450 (CYP) enzyme family is regulated by numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in both humans and animals. However, the coordinated regulation of CYP, CYP-regulating transcription factors, and transcriptional co-factors in the liver linking energy metabolism to detoxification has never been investigated. Interleukin-6 (IL-6) has been suggested to be released during fasting and has been shown to regulate CYP expression. The present study investigated the mRNA content of selected CYP, AhR, CAR, PXR and PPARα in mice fasted for 18hours and subsequently exposed to IL-6...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29030271/noael-dose-of-a-neonicotinoid-pesticide-clothianidin-acutely-induce-anxiety-related-behavior-with-human-audible-vocalizations-in-male-mice-in-a-novel-environment
#3
Tetsushi Hirano, Shogo Yanai, Tadashi Takada, Naoki Yoneda, Takuya Omotehara, Naoto Kubota, Kiichi Minami, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi
Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29030270/preliminary-data-on-citrinin-kinetics-in-humans-and-their-use-to-estimate-citrinin-exposure-based-on-biomarkers
#4
Gisela H Degen, Nurshad Ali, Ursula Gundert-Remy
Citrinin (CIT), a fungal metabolite causing nephrotoxicity, has a tolerable daily intake (TDI) value of 0.2μg/kg bw. Contamination of food with CIT is not sufficiently known to allow dietary exposure assessment. Urinary biomonitoring data are available from cohorts of several countries. However, kinetic information is lacking for CIT, hampering the use of urinary biomonitoring data to estimate the daily intake. We have investigated the kinetics of CIT after oral intake in two human volunteers on two occasions...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29030269/the-importance-of-inclusion-of-kinetic-information-in-the-extrapolation-of-high-to-low-concentrations-for-human-limit-setting
#5
Liesbeth Geraets, Marco J Zeilmaker, Peter M J Bos
Human health risk assessment of inhalation exposures generally includes a high-to-low concentration extrapolation. Although this is a common step in human risk assessment, it introduces various uncertainties. One of these uncertainties is related to the toxicokinetics. Many kinetic processes such as absorption, metabolism or excretion can be subject to saturation at high concentration levels. In the presence of saturable kinetic processes of the parent compound or metabolites, disproportionate increases in internal blood or tissue concentration relative to the external concentration administered may occur resulting in nonlinear kinetics...
October 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29024790/dna-methylation-and-potential-multigenerational-epigenetic-effects-linked-to-uranium-chronic-low-dose-exposure-in-gonads-of-males-and-females-rats
#6
REVIEW
G Elmhiri, C Gloaguen, S Grison, D Kereselidze, C Elie, K Tack, M Benderitter, P Lestaevel, A Legendre, M Souidi
INTRODUCTION: An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways...
October 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29024789/in-vitro-pharmacological-characterization-of-the-bispyridinium-non-oxime-compound-mb327-and-its-2-and-3-regioisomers
#7
K V Niessen, T Seeger, S Rappenglück, T Wein, G Höfner, K T Wanner, H Thiermann, F Worek
The primary toxic mechanism of organophosphorus compounds, i.e. nerve agents or pesticides, is based on the irreversible inhibition of acetylcholinesterase. In consequence of the impaired hydrolysis, the neurotransmitter acetylcholine accumulates in cholinergic synapses and disturbs functional activity of nicotinic and muscarinic acetylcholine receptors by overstimulation and subsequent desensitization. The resulting cholinergic syndrome will become acute life-threatening, if not treated adequately. The current standard treatment, consisting of administration of a competitive mAChR antagonist (e...
October 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29017960/upper-respiratory-tract-nociceptor-stimulation-and-stress-response-following-acute-and-repeated-cyfluthrin-inhalation-in-normal-and-pregnant-rats-physiological-rat-specific-adaptions-can-easily-be-misunderstood-as-adversities
#8
Juergen Pauluhn
This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroexcitatory afferent sensory stimulus from peripheral nociceptors in the upper respiratory tract is likely to be perceived as a transient stimulus triggering annoyance and/or avoidance by both rats and humans...
October 7, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29017959/8-isoprostane-is-an-early-biomarker-for-oxidative-stress-in-chlorine-induced-acute-lung-injury
#9
Linda Elfsmark, Lina Ågren, Christine Akfur, Anders Bucht, Sofia Jonasson
Inhalation of chlorine (Cl2) may cause oxidative acute lung injury (ALI) characterized by pulmonary edema, pneumonitis, and hyperreactive airways. The aim of the study was to identify possible biomarkers for Cl2-induced ALI. Female BALB/c mice were exposed to Cl2 for 15min using two protocols 1) concentration-dependent response (25-200ppm) and 2) time-kinetics (2h-14days post-exposure). Exposure to 50-200ppm Cl2 caused a concentration-dependent inflammatory response with increased expression of IL-1β, IL-6 and CXCL1/KC in bronchoalveolar lavage fluid 2-6h after exposure which was followed by increased lung permeability and a neutrophilic inflammation 12-24h post-exposure...
October 7, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28993240/the-oximes-hi-6-and-mmb-4-fail-to-reactivate-soman-inhibited-human-and-guinea-pig-ache-a-kinetic-in-vitro-study
#10
Franz Worek, Horst Thiermann, Timo Wille
Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. However, in vivo studies in various, soman poisoned animal species showed a therapeutic effect of oximes, with the exact mechanism of this effect remaining still unclear. In order to get more insight and a basis for the extrapolation of animal data to humans, we applied a dynamic in vitro model with continuous online determination of AChE activity...
October 6, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28988819/an-in-vitro-cytotoxic-approach-to-assess-the-toxicity-of-heavy-metals-and-their-binary-mixtures-on-hippocampal-ht-22-cell-line
#11
Venkatanaidu Karri, Vikas Kumar, David Ramos, Eliandre Oliveira, Marta Schuhmacher
Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on the toxicity of mixtures. In this study, four common neurotoxicity heavy metals lead (Pb) cadmium (Cd), arsenic (As), and methylmercury (MeHg) were exposed individually and as mixtures to HT-22 cell line for 8days. The study established that low dose exposures induced toxicity to the HT-22 cell line during 8days. The results indicates potency dependent response, the toxicity of single metals on the HT-22 cells; MeHg > As > Cd > Pb...
October 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28987480/egg-white-derived-peptides-prevent-cardiovascular-disorders-induced-by-mercury-in-rats-role-of-angiotensin-converting-enzyme-ace-and-nadph-oxidase
#12
Danize Aparecida Rizzetti, Ángela Martín, Patricia Corrales, Francisca Fernandez, Maylla Ronacher Simões, Franck Maciel Peçanha, Dalton Valentim Vassallo, Marta Miguel, Giulia Alessandra Wiggers
The study aimed to investigate the effects of egg white hydrolysate (EWH) on vascular disorders induced by mercury (Hg). For this, male Wistar rats were treated for 60days: Untreated (saline, i.m.); Mercury (HgCl2, i.m., 1st dose 4.6μg/kg, subsequent doses 0.07μg/kg/day); Hydrolysate (EWH, gavage, 1g/kg/day); Hydrolysate-Mercury. Systolic (SBP) and diastolic (DBP) blood pressure measurement and vascular reactivity experiments in aorta were performed. We analyzed endothelial dependent and independent vasodilator responses and vasoconstrictor response to phenylephrine (Phe) in absence and presence of endothelium, a NOS inhibitor, a NADPH oxidase inhibitor, the superoxide dismutase, a non-selective COX inhibitor, a selective COX-2 inhibitor, an AT-1 receptors blocker...
October 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28965971/combined-low-dose-zearalenone-and-aflatoxin-b1-on-cell-growth-and-cell-cycle-progression-in-breast-cancer-mcf-7-cells
#13
Ka Yiu Yip, Murphy Lam Yim Wan, Alice Sze Tsai Wong, Kenneth S Korach, Hani El-Nezami
Zearalenone (ZEA) has long been recognized as a xenoestrogen, while the endocrine disrupting effects of aflatoxin B1 (AFB1) have been identified recently. Due to co-occurrence and endocrine disrupting potentials of ZEA and AFB1, it was hypothesized that co-exposure to ZEA and AFB1 might affect breast cancer cell growth. Consequently, the aim of this study was to evaluate the combined effects of ZEA and AFB1 (1nM-100nM) on cell growth and cell cycle progression, using a human breast cancer cell line MCF-7. Our results showed that ZEA and AFB1 produced significant interactive effects on cell growth, DNA synthesis and cell cycle progression...
September 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28964810/the-tobacco-carcinogen-nnk-disturbs-mitotic-chromosome-alignment-by-interrupting-p53-targeting-to-the-centrosome
#14
Ji Eun Park, Yu Lim Jang, Chang-Young Jang
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most potent risk factor among tobacco-related carcinogens in lung cancer progression and outcomes. Although genetic mutations and chromosome instability have been detected in NNK-induced lung tumors, the oncogenic mechanisms of NNK are not fully understood. Here, we show that NNK increases chromosomal instability by disrupting spindle microtubule (MT) attachment to the kinetochore (KT) and spindle dynamics. Mechanistically, NNK blocks the targeting of p53 to the centrosome during mitosis, leading to chromosome alignment defects in metaphase...
September 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28964808/acanthoic-acid-protectsagainst-ethanol-induced-liver-injury-possible-role-of-ampk-activation-and-irak4-inhibition
#15
You-Li Yao, Xin Han, Jian Song, Jing Zhang, Ya-Mei Li, Li-Hua Lian, Yan-Ling Wu, Ji-Xing Nan
The aim of this study was to investigate the effects of acanthoic acid (AA) on the regulation of inflammatory response, lipid accumulation, and fibrosis via AMPK- IRAK4 signaling against chronic alcohol consumption in mice. Ethanol-induced liver injury was induced in male mice by Lieber-DeCarli diet for 28d. And mice in AA groups were gavaged with AA (20 or 40mg/kg) for 28d. AA treatment significantly decreased serum AST and TG, hepatic TG levels, serum ethanol and LPS levels compared with chronic ethanol administration...
September 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28964811/chemical-stability-of-reactive-skin-decontamination-lotion-rsdl-%C3%A2
#16
R Bogan, H J Maas, T Zimmermann
Reactive Skin Decontamination Lotion (RSDL(®)) is used for the decontamination of Chemical Warfare Agents and Toxic Industrial Compounds after dermal exposure. It has to be stockpiled over a long period and is handled in all climatic zones. Therefore stability is an essential matter of concern. In this work we describe a study to the chemical stability of RSDL(®) as basis for an estimation of shelf life. We analysed RSDL(®) for the active ingredient 2,3-butandione monoxime (diacetylmonooxime, DAM), the putative degradation product dimethylglyoxime (DMG) and unknown degradation products by means of a reversed phase high pressure liquid chromatography (HPLC)...
September 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28964809/continuous-soy-isoflavones-exposure-from-weaning-to-maturity-induces-downregulation-of-ovarian-steroidogenic-factor-1-gene-expression-and-corresponding-changes-in-dna-methylation-pattern
#17
Wenxiang Wang, Yan Sun, Yiwei Guo, Ping Cai, Yuchen Li, Jin Liu, Guoxi Cai, Aoyagi Kiyoshi, Wenchang Zhang
Female Wistar rats were treated with orally administered soy isoflavones at concentrations of 0, 25, 50, or 100mg/kg body weight from weaning until sexual maturity (3 mo.), and ovarian steroidogenesis was evaluated. After soy isoflavones were administered, a significant (P<0.05) decrease (44%) in the serum estrodial levels of the high-dose (HD) group were observed. Cultured granulosa cells from the middle- (MD) and HD groups showed significantly (P<0.05) reduced (31%, 45%, respectively) in vitro estradiol secretion, and those from the HD group showed significantly (P<0...
September 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28958773/pathophysiological-central-nervous-system-changes-in-a-porcine-model-of-acetaminophen-induced-acute-liver-failure
#18
Christian Thiel, Johannes Lauber, Wilfried Klingert, Kathrin Klingert, Matthias H Morgalla, Rudi Beschorner, Andreas Peter, Christian Grasshoff, Alfred Königsrainer, Martin Schenk, Karolin Thiel
BACKGROUND: Critical care management of patients suffering from acute liver failure (ALF) continues to be challenging. Animal models studying the pathophysiological central nervous system alterations during the course of ALF provide an opportunity to improve diagnostic and therapeutic strategies. The aim of this study was to analyse the course of cerebral oxygenation in addition to conventional neuromonitoring during the course of acetaminophen-induced ALF. METHODS: ALF was induced by intrajejunal acetaminophen administration in 20 German landrace pigs...
September 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28947270/a-novel-in-vivo-model-for-predicting-myelotoxicity-of-chemotherapeutic-agents-using-il-3-gm-csf-transgenic-humanized-mice
#19
R Ito, D Nagai, N Igo, Y Okuda, K Sekine, E Ichimura, I Katano, T Mizushima, M Goto, Y Ohnishi, M Ito, K Okamoto
Evaluating myelotoxicity is essential for ensuring the safety of novel drugs before they are approved for clinical applications. Although in vivo prediction of the maximum tolerated doses (MTDs) of anticancer drugs is usually performed in rodents, the results are not always applicable to clinical treatment because drugs may have different effects in human and rodent cells. Previously, we generated a human IL-3 and GM-CSF transgenic humanized mouse (hu-IL-3/GM Tg), in which human granulocytes effectively differentiated after hematopoietic stem cell transplantation...
September 22, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28943392/an-integrative-analysis-of-chemically-induced-cirrhosis-associated-hepatocarcinogenesis-histological-biochemical-and-molecular-features
#20
Guilherme Ribeiro Romualdo, Tony Fernando Grassi, Renata Leme Goto, Mariana Baptista Tablas, Lucas Tadeu Bidinotto, Ana Angélica Henrique Fernandes, Bruno Cogliati, Luís Fernando Barbisan
This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2)...
September 21, 2017: Toxicology Letters
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