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Toxicology Letters

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https://www.readbyqxmd.com/read/28602893/daily-uptake-of-mycotoxins-tdi-might-not-be-protective-for-nursed-infants
#1
G H Degen, F Partosch, K Muñoz, U Gundert-Remy
Exclusive breast feeding is recommended by international bodies for the first six months of life. Because of the presence of contaminants, breast feeding might lead to toxicologically relevant exposure of the nursed child. Exposure towards mycotoxins is of specific interest because of their widespread occurrence in food and of their toxicological profile. We calculated the relationship between maternal intake at the level of the existing TDIs and the exposure in the nursed infants of several mycotoxins to evaluate whether maternal exposure at the TDI is also safe for the nursed infant...
June 7, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28596144/serum-protein-expression-profiling-and-bioinformatics-analysis-in-workers-occupationally-exposed-to-chromium-vi
#2
Guiping Hu, Tianjing Wang, Jiaxing Liu, Zhangjian Chen, Lijun Zhong, Shanfa Yu, Zuchang Zhao, Min Zhai, Guang Jia
Cr(VI) is widely-recognized as occupational and environmental contaminant, but the precise underlying mechanisms of Cr(VI) induced carcinogenic toxicity remain to be elucidated. Among kinds of toxic mechanisms, alteration of protein profiling usually elaborate a key mechanism of Cr(VI) induced toxicity and carcinogenesis. Large-scale proteins changes can reflect the onset or progression of carcinogenic toxicity, and potential serum protein biomarkers of Cr(VI) exposure. To gain an insight into the serum proteins expression profiling in chromate workers and find potential novel serum proteins biomarkers of Cr(VI) exposure, 107 male participants from a chromate production plant were recruited into the study...
June 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28579487/intoxication-by-gamma-hydroxybutyrate-and-related-analogues-clinical-characteristics-and-comparison-between-pure-intoxication-and-that-combined-with-other-substances-of-abuse
#3
Òscar Miró, Miguel Galicia, Paul Dargan, Alison M Dines, Isabelle Giraudon, Fridtjof Heyerdahl, Knut E Hovda, Christopher Yates, David M Wood
OBJECTIVE: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse. METHOD: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes...
June 1, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28571686/agonistic-and-antagonistic-effects-of-phthalates-and-their-urinary-metabolites-on-the-steroid-hormone-receptors-er%C3%AE-er%C3%AE-and-ar
#4
Anika Engel, Thorsten Buhrke, Francine Imber, Sönke Jessel, Albrecht Seidel, Wolfgang Völkel, Alfonso Lampen
Phthalate plasticizers have been reported to exert adverse effects via activation of the estrogen receptors ERα and ERβ and inhibition of the androgen receptor AR as molecular initiating events. After oral uptake, phthalates are metabolized to their corresponding monoesters and subsequently to oxidized phthalate monoester derivatives, which are in turn conjugated to glucuronic acid and finally excreted with the urine. In contrast to the parent phthalates, toxicological data regarding their primary and secondary metabolites are rare...
May 29, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28571685/activation-of-the-aryl-hydrocarbon-receptor-decreases-rifampicin-induced-cyp3a4-expression-in-primary-human-hepatocytes-and-heparg
#5
Martin Krøyer Rasmussen, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin
The role of the cross-talk between nuclear receptors in the regulation of Cytochrome P450 expression in the liver is well-documented. Most studies have focused on the cross-talk between the pregnane X receptor (PXR) and other receptors, such as the constitutive androstane receptor. However, cross-talk between PXRs and aryl hydrocarbon receptors (AhRs) has also been suggested, but reports regarding this cross-talk are conflicting. In the present study, we treated HepaRG and primary human hepatocytes (PHHs) with both a strong (TCDD) and weak (3-methylindole; 3MI) AhR activator to investigate their impact on PXR-regulated expression of CYP3A4...
May 29, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28559121/calpain-2-p35-p25-cdk5-pathway-is-involved-in-the-neuronal-apoptosis-induced-by-polybrominated-diphenyl-ether-153
#6
Hongmei Zhang, Lijun Chang, Huajun Zhang, Jisheng Nie, Zhihong Zhang, Xiaorong Yang, Ann M Vuong, Zemin Wang, Aimin Chen, Qiao Niu
Polybrominated diphenyl ethers (PBDEs) have been demonstrated to induce neurotoxicity in experimental rats and mice, with neuronal apoptosis as one of the major mechanisms, however, the mechanisms underlying PBDEs-induced neuronal apoptosis remain unclear. In this study, we aimed to investigate the role of calpain/p35-p25/Cdk5 pathway in BDE-153-induced neuronal apoptosis in the hippocampus and primary neurons in rats. Results showed that compared to the controls, neuronal apoptosis was significantly increased in vivo and ex vivo, as manifested by the increased hippocampus TUNEL-positive cell rates, apoptotic neurons in Hoechst and AO/EB staining, and the increased LDH activity and percentage of Annexin V-positive cells in rat hippocampus and primary neurons...
May 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28552774/uptake-of-perfluorooctanoic-acid-by-caco-2-cells-involvement-of-organic-anion-transporting-polypeptides
#7
Osamu Kimura, Yukiko Fujii, Koichi Haraguchi, Yoshihisa Kato, Chiho Ohta, Nobuyuki Koga, Tetsuya Endo
The mechanism underlying the intestinal absorption of perfluorooctanoic acid (PFOA) was investigated using Caco-2 cells. The uptake of PFOA from the apical membrane of Caco-2 cells was fast, and pH, temperature, and concentration dependent, but Na(+) independent. Coincubation with sulfobromophthalein (BSP), glibenclamide, estron-3-sulfate, cyclosporine A or rifamycin SV, which are typical substrates or inhibitors of organic anion transporting polypeptides (OATPs), significantly decreased the uptake of PFOA...
May 25, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28552773/voltage-gated-ion-channels-blockade-is-the-underlying-mechanism-of-bimu8-induced-cardiotoxicity
#8
Shahid Muhammad Iqbal, Rosa Lemmens-Gruber
BIMU8 is a 5-HT4a receptor agonist and used as an experimental drug to counteract opioid induced respiratory depression. In preliminary experiments serious disturbances in ECG were observed in anesthetized rabbits which prompted us to explore the underlying cause of BIMU8 induced abnormal changes in ECG recordings. Electrophysiological experiments were performed on HEK-293 cells expressing hERG, CaV1.2 and NaV1.5 ion channels. In whole-cell recordings BIMU8 effectively blocked these three channels, with IC50 values of 0...
May 25, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#9
Dai Sig Im, Hye Jin Shin, Keum Jin Yang, So Young Jung, Ho Yeon Song, Hyeon Seok Hwang, Hyo-Wook Gil
BACKGROUND: Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates p-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice...
May 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28522410/a-global-human-health-risk-assessment-for-octamethylcyclotetrasiloxane-d4
#10
Robinan Gentry, Allison Franzen, Cynthia Van Landingham, Tracy Greene, Kathy Plotzke
Octamethylcyclotetrasiloxane (D4) is a low-molecular-weight volatile cyclic siloxane, primarily used as an intermediate in the production of some widely-used industrial and consumer silicone based polymers and may be present as a component in a variety of consumer products. A global "harmonized" risk assessment was conducted to meet requirements for substance-specific risk assessments conducted by regulatory agencies such as USEPA's Integrated Risk Information System (IRIS), Health Canada's Chemical Management Program (CMP) and various independent scientific committees of the European Commission (e...
May 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28511864/metabolism-and-disposition-of-14-c-methycyclosiloxanes-in-rats
#11
Jeanne Y Domoradzki, Christopher M Sushynski, Jacob M Sushynski, Debra A McNett, Cynthia Van Landingham, Kathleen P Plotzke
Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) are low molecular weight cyclic volatile methyl siloxanes (cVMSs) primarily used as intermediates or monomers in the production of high molecular weight silicone polymers. The use of D4 as a direct ingredient in personal care products has declined significantly over the past 10 years, although it may be present as a residual impurity in a variety of consumer products. D5 is still used as an intentional ingredient in cosmetics, consumer products and in dry cleaning...
May 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28499612/environmentally-relevant-dose-of-arsenic-interferes-in-functions-of-human-monocytes-derived-dendritic-cells
#12
Abbas Bahari, Vahid Salmani
Arsenic is a major environmental pollutant and highly hazardous toxin to human health, which well established as carcinogen and immune deregulatory properties. Dendritic cells (DCs) have a pivotal role in cell-mediated immunity for T-cell activation and antigen presentation. In this study, T cell activation, some key functional genes expression, cell stability and phagocytosis capacity of human monocytes derived DCs (MDDCs) were analyzed after in vitro exposure to very low dose of arsenic for 12 and 24h. Arsenic decreased continually phagocytosis capacity of MDDCs...
May 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28499610/effects-of-cyanobacteria-oscillatoria-sp-lipopolysaccharide-on-b-cell-activation-and-toll-like-receptor-4-signaling
#13
Michelle Swanson-Mungerson, Ryan Incrocci, Vijay Subramaniam, Philip Williams, Mary L Hall, Alejandro M S Mayer
Cyanobacteria ("blue-green algae"), such as Oscillatoria sp., are a ubiquitous group of bacteria found in freshwater systems worldwide that are linked to illness and in some cases, death among humans and animals. Exposure to cyanobacteria occurs via ingestion of contaminated water or food-products. Exposure of the gut to these bacteria also exposes their toxins, such as lipopolysaccharide (LPS), to B cells in the gut associated lymphoid tissue. However, the effect of Oscillatoria sp. LPS on B cell activation is unknown...
May 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28495614/protective-potential-of-different-compounds-and-their-combinations-with-mesna-against-sulfur-mustard-induced-cytotoxicity-and-genotoxicity
#14
Petr Jost, Petra Fikrova, Hana Svobodova, Jaroslav Pejchal, Rudolf Stetina
The purpose of this study was to evaluate the efficacy of potential candidate molecules or their combinations against strong alkylation agent sulfur mustard (SM) on the human lung alveolar epithelial cell line A-549. Candidate molecules were chosen on the basis of their previously observed protective effects in vitro. The tested compounds, including antioxidants, sulfhydryl or other sulfur-containing molecules, nitrogen-containing molecules, PARP inhibitors and a NO synthase inhibitor, were applicated 30min before SM treatment...
May 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28478158/mechanism-of-triclosan-toxicity-mitochondrial-dysfunction-including-complex-ii-inhibition-superoxide-release-and-uncoupling-of-oxidative-phosphorylation
#15
Vera V Teplova, Konstantin N Belosludtsev, Alexey G Kruglov
Triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol), a widely used antibacterial agent, exerts adverse effects on the organism of mammals. Recent research reviled that triclosan at low micromolar concentrations causes mitochondrial dysfunction in many cell types, but the mechanisms of its effect are not fully understood. Here we show that exposure to triclosan disrupted membrane potential, prevented the calcium uptake-driven high-amplitude mitochondrial swelling, stimulated the respiration in the presence of complex I substrates, and suppressed the ADP-stimulated respiration in the presence of complex II substrate, succinate...
May 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28478157/human-glutathione-s-transferases-and-nad-p-h-quinone-oxidoreductase-1-catalyzed-inactivation-of-reactive-quinoneimines-of-amodiaquine-and-n-desethylamodiaquine-possible-implications-for-susceptibility-to-amodiaquine-induced-liver-toxicity
#16
Yongjie Zhang, Shalenie P den Braver-Sewradj, J Chris Vos, Nico P E Vermeulen, Jan N M Commandeur
Amodiaquine (AQ), an antimalarial drug, widely prescribed in endemic areas of Africa and Asia, is used in combination with artesunate as recommended by the WHO. However, due to its idiosyncratic hepatotoxicity and agranulocytosis, the therapeutic use has been discontinued in most countries. Oxidative bioactivation to protein-reactive quinonimines (QIs) by hepatic cytochrome P450s and myeloperoxidase (MPO) have been suggested to be important mechanisms underlying AQ idiosyncratic toxicity. However, the inactivation of the reactive QIs by detoxifying enzymes such as human glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreducatase 1 (NQO1) has not been characterized yet...
May 3, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28478156/activated-thyroid-hormone-receptor-modulates-dioxin-inducible-aryl-hydrocarbon-receptor-mediated-cyp1a1-induction-in-human-hepatocytes-but-not-in-human-hepatocarcinoma-hepg2-cells
#17
Radim Vrzal, Aneta Vrzalova, Aneta Grycova, Zdenek Dvorak
Aryl hydrocarbon receptor (AhR) is a transcription factor, the activity of which is modulated by hormones including glucocorticoids and estrogens. In this study, we examined the effects of triiodothyronine (T3), a ligand and activator of thyroid hormone receptor (TR), on transcriptional activity of AhR and the expression of its target gene CYP1A1. Study was carried out in human hepatocellular carcinoma cells HepG2 and primary cultures of human hepatocytes (HH). Gene reporter assay in stably transfected AZ-AhR cells revealed that T3 dose-dependently augmented 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible AhR-dependent luciferase activity...
May 3, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28465191/activity-of-cholinesterases-in-a-young-and-healthy-middle-european-population-relevance-for-toxicology-pharmacology-and-clinical-praxis
#18
Jana Zdarova Karasova, Zuzana Maderycova, Martina Tumova, Daniel Jun, Vit Rehacek, Kamil Kuca, Jan Misik
The activity of human cholinesterases, erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and plasma butyrylcholinesterase (BChE; EC 3.1.1.8) represents an important marker when monitoring exposure to pesticides/nerve agents, and may also be used in occupational medicine in diagnosis and prognosis of some diseases. In this study "normal/baseline" AChE and BChE activity has been investigated in a young and healthy population, with subsequent evaluation of several intra-population factors including sex, age (categories 18-25, 26-35 and 36-45 years old) and smoker status...
April 30, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28460337/corrigendum-to-risk-assessment-in-combustion-toxicology-should-carbon-dioxide-be-recognized-as-a-modifier-of-toxicity-or-separate-toxicological-entity-toxicol-lett-262-2016-142-152
#19
https://www.readbyqxmd.com/read/28456571/erythropoietin-activates-sirt1-to-protect-human-cardiomyocytes-against-doxorubicin-induced-mitochondrial-dysfunction-and-toxicity
#20
Lan Cui, Jiabin Guo, Qiang Zhang, Jian Yin, Jin Li, Wei Zhou, Tingfen Zhang, Haitao Yuan, Jun Zhao, Li Zhang, Paul L Carmichael, Shuangqing Peng
The hormone erythropoietin (EPO) has been demonstrated to protect against chemotherapy drug doxorubicin (DOX)-induced cardiotoxicity, but the underlying mechanism remains obscure. We hypothesized that silent mating type information regulation 2 homolog 1 (SIRT1), an NAD(+)-dependent protein deacetylase that activates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), plays a crucial role in regulating mitochondrial function and mediating the beneficial effect of EPO. Our study in human cardiomyocyte AC16 cells showed that DOX-induced cytotoxicity and mitochondrial dysfunction, as manifested by decreased mitochondrial DNA (mtDNA) copy number, mitochondrial membrane potential, and increased mitochondrial superoxide accumulation, can be mitigated by EPO pretreatment...
April 27, 2017: Toxicology Letters
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