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Archives of Toxicology

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https://www.readbyqxmd.com/read/28210754/targeted-lipidomics-profiling-of-acute-arsenic-exposure-in-mice-serum-by-on-line-solid-phase-extraction-stable-isotope-dilution-liquid-chromatography-tandem-mass-spectrometry
#1
Chao-Yu Chen, Pinpin Lin, Ming-Hsien Tsai, Hui-Ling Lee
Lipidomics is the area of study dedicated to the comprehensive analysis and characterization of the functions and metabolism of lipids in biological samples. One of the most comprehensively studied classes of lipids is polyunsaturated fatty acids (PUFAs). Eicosanoids are a series of bioactive lipid mediators that are metabolized from PUFAs and generated majorly from the precursor arachidonic acid. This study identified the profiles of target eicosanoids after acute exposure to arsenic. The principle objective was to determine and validate 10 eicosanoids in mouse serum using on-line solid-phase extraction integrated with liquid chromatography-electrospray tandem mass spectrometry...
February 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28204865/prediction-of-human-sensory-irritation-due-to-ethyl-acrylate-the-appropriateness-of-time-weighted-average-concentration%C3%A2-%C3%A3-%C3%A2-time-models-for-varying-concentrations
#2
Stefan Kleinbeck, Michael Schäper, Anna Zimmermann, Meinolf Blaszkewicz, Thomas Brüning, Christoph van Thriel
Human data about the potency of ethyl acrylate to evoke sensory irritation is currently not available. Therefore, we conducted an experimental exposure study and the magnitude of chemosensory effects in healthy human volunteers was mathematically modeled by combining the factors current concentration (c) and duration/time (t). In a repeated-measures design, 19 subjects were exposed for 4 h to constant and varying concentrations (including peaks of 5 and 10 ppm) of ethyl acrylate with either a 2.5 or 5 ppm time-weighted average (TWA) concentration...
February 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28204864/high-bioavailability-curcumin-an-anti-inflammatory-and-neurosupportive-bioactive-nutrient-for-neurodegenerative-diseases-characterized-by-chronic-neuroinflammation
#3
REVIEW
Faheem Ullah, Andy Liang, Alejandra Rangel, Erika Gyengesi, Garry Niedermayer, Gerald Münch
Neuroinflammation is a pathophysiological process present in a number of neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, traumatic brain injury including chronic traumatic encephalopathy and other age-related CNS disorders. Although there is still much debate about the initial trigger for some of these neurodegenerative disorders, during the progression of disease, broad range anti-inflammatory drugs including cytokine suppressive anti-inflammatory drugs (CSAIDs) might be promising therapeutic options to limit neuroinflammation and improve the clinical outcome...
February 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28197649/dose-response-relationship-of-temozolomide-determined-by-the-pig-a-comet-and-micronucleus-assay
#4
M Guérard, G Johnson, S Dertinger, G Duran-Pacheco, J Funk, A Zeller
Temozolomide (TMZ), a monofunctional alkylating agent, was selected as a model compound to determine its quantitative genotoxic dose-response relationship in different tissues (blood, liver, and jejunum) and endpoints [Pig-a-, comet-, and micronucleus assay (MNT)] in male rats. TMZ was administered p.o. over 5 consecutive days (day 1-5), followed by a treatment-free period of 50 days (day 6-56) and a final administration prior to necropsy (day 57-59). TMZ showed a dose-dependent increase in DNA damage in all interrogated endpoints...
February 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28188341/evaluation-of-transcriptomic-signature-as-a-valuable-tool-to-study-drug-induced-cholestasis-in-primary-human-hepatocytes
#5
Céline Parmentier, Philippe Couttet, Armin Wolf, Thomas Zaccharias, Bruno Heyd, Philippe Bachellier, Marianne Uteng, Lysiane Richert
Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1-3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated...
February 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28180949/toxicity-of-two-classes-of-arsenolipids-and-their-water-soluble-metabolites-in-human-differentiated-neurons
#6
Barbara Witt, Sören Meyer, Franziska Ebert, Kevin A Francesconi, Tanja Schwerdtle
Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAs(III)) in fully differentiated human brain cells (LUHMES cells)...
February 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28180948/tributyltin-exposure-at-noncytotoxic-doses-dysregulates-pancreatic-%C3%AE-cell-function-in-vitro-and-in-vivo
#7
Ya-Wen Chen, Kuo-Cheng Lan, Jing-Ren Tsai, Te-I Weng, Ching-Yao Yang, Shing-Hwa Liu
Tributyltin (TBT) is an endocrine disruptor. TBT can be found in food and in human tissues and blood. Several animal studies revealed that organotins induced diabetes with decreased insulin secretion. The detailed effect and mechanism of TBT on pancreatic β-cell function still remain unclear. We investigated the effect and mechanism of TBT exposure at noncytotoxic doses relevant to human exposure on β-cell function in vitro and in vivo. The β-cell-derived RIN-m5F cells and pancreatic islets from mouse and human were treated with TBT (0...
February 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28180947/safeguarding-human-health-using-in-silico-tools
#8
EDITORIAL
Melissa Van Bossuyt, Els Van Hoeck, Tamara Vanhaecke, Vera Rogiers, Birgit Mertens
No abstract text is available yet for this article.
February 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28180946/new-developments-and-directions-in-the-clinical-application-of-the-echinocandins
#9
REVIEW
C C Chang, M A Slavin, S C-A Chen
The echinocandins-caspofungin, anidulafungin and micafungin-are semi-synthetic cyclic hexapeptide antimicrobial agents with modified N-linked acyl lipid side chains which anchor the compounds to the phospholipid bilayer of the fungal cell membrane, thereby inhibiting synthesis of fungal cell wall glucan. Over the last 10 years, echinocandins have become the first-line antifungal treatment of candidaemia and other forms of invasive candidiasis (IC). Echinocandins are generally well tolerated, but their use is limited by their requirement for daily intravenous dosing, lack of oral formulation and limited spectrum...
February 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28175954/multiple-resistance-to-carcinogens-and-xenobiotics-p-glycoproteins-as-universal-detoxifiers
#10
REVIEW
Thomas Efferth, Manfred Volm
The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR)...
February 7, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28160022/role-of-human-sulfotransferase-1a1-and-n-acetyltransferase-2-in-the-metabolic-activation-of-16-heterocyclic-amines-and-related-heterocyclics-to-genotoxicants-in-recombinant-v79-cells
#11
Matthieu Chevereau, Hansruedi Glatt, Daniel Zalko, Jean-Pierre Cravedi, Marc Audebert
Heterocyclic aromatic amines (HAAs) are primarily produced during the heating of meat or fish. HAAs are mutagenic and carcinogenic, and their toxicity in model systems depend on metabolic activation. This activation is mediated by cytochrome P450 (CYP) enzymes, in particular CYP1A2. Some studies have indicated a role of human sulfotransferase (SULT) 1A1 and N-acetyltransferase (NAT) 2 in the terminal activation of HAAs. In this study, we conducted a metabolism/genotoxicity relationship analysis for 16 HAAs and related heterocyclics...
February 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28160021/are-multitasking-abilities-impaired-in-welders-exposed-to-manganese-translating-cognitive-neuroscience-to-neurotoxicology
#12
Christoph van Thriel, Clara Quetscher, Beate Pesch, Anne Lotz, Martin Lehnert, Swaantje Casjens, Tobias Weiss, Rainer Van Gelder, Katrin Plitzke, Thomas Brüning, Christian Beste
Manganese (Mn) is an essential trace element with well characterized neurotoxic effects in high concentrations. Neurochemically, the initial neurotoxic effect of Mn is the perturbation of striatal γ-aminobutyric acid levels. Specific tasks for the assessment of cognitive functions subserved by fronto-striatal loops are available as the stop-change task (SCT) assessing control of multi-component behavior and action cascading. In a cross-sectional study, fifty male welders and 28 age-matched controls completed the SCT during a whole day examination...
February 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28133701/comparative-proteomic-analysis-of-2-mcpd-and-3-mcpd-induced-heart-toxicity-in-the-rat
#13
Katharina Schultrich, Falko Frenzel, Axel Oberemm, Thorsten Buhrke, Albert Braeuning, Alfonso Lampen
The chlorinated propanols 2- and 3-monochloropropanediol (MCPD), and their fatty acid esters have gained public attention due to their frequent occurrence as heat-induced food contaminants. Toxic properties of 3-MCPD in kidney and testis have extensively been characterized. Other 3-MCPD target organs include heart and liver, while 2-MCPD toxicity has been observed in striated muscle, heart, kidney, and liver. Inhibition of glycolysis appears to be important in 3-MCPD toxicity, whereas mechanisms of 2-MCPD toxicity are still unknown...
January 30, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28130581/susceptibility-to-chronic-inflammation-an-update
#14
REVIEW
Noha Ahmed Nasef, Sunali Mehta, Lynnette R Ferguson
Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed...
January 27, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28120037/long-term-accumulation-of-diphenylarsinic-acid-in-the-central-nervous-system-of-cynomolgus-monkeys
#15
Tomoyuki Masuda, Kazuhiro Ishii, Yasuo Seto, Tomoko Hosoya, Ryuta Tanaka, Tomohiro Nakayama, Nobuaki Iwasaki, Yasuyuki Shibata, Akira Tamaoka
Diphenylarsinic acid (DPAA) is an organic arsenic compound used for the synthesis of chemical weapons. We previously found that the residents of Kamisu city in Ibaraki Prefecture, Japan, were exposed to DPAA through contaminated well water in 2003. Although mounting evidence strongly suggests that their neurological symptoms were caused by DPAA, the dynamics of DPAA distribution and metabolism after ingestion by humans remain to be elucidated. To accurately predict the distribution of DPAA in the human body, we administrated DPAA (1...
January 25, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28110405/cyanotoxins-producing-organisms-occurrence-toxicity-mechanism-of-action-and-human-health-toxicological-risk-evaluation
#16
REVIEW
Franca M Buratti, Maura Manganelli, Susanna Vichi, Mara Stefanelli, Simona Scardala, Emanuela Testai, Enzo Funari
Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock...
January 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28091709/use-of-in-silico-models-for-prioritization-of-heat-induced-food-contaminants-in-mutagenicity-and-carcinogenicity-testing
#17
Falko Frenzel, Thorsten Buhrke, Irina Wenzel, Jennifer Andrack, Jan Hielscher, Alfonso Lampen
Numerous Maillard reaction and lipid oxidation products are present in processed foods such as heated cereals, roasted meat, refined oils, coffee, and juices. Due to the lack of experimental toxicological data, risk assessment is hardly possible for most of these compounds. In the present study, an in silico approach was employed for the prediction of the toxicological endpoints mutagenicity and carcinogenicity on the basis of the structure of the respective compound, to examine (quantitative) structure-activity relationships for more than 800 compounds...
January 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28070599/organophosphate-neurotoxicity-to-the-voluntary-motor-system-on-the-trail-of-environment-caused-amyotrophic-lateral-sclerosis-the-known-the-misknown-and-the-unknown
#18
Samantha J Merwin, Teresa Obis, Yanelli Nunez, Diane B Re
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder. It is characterized by progressive degeneration of the motor neurons controlling voluntary movement. The underlying mechanisms remain elusive, a fact that has precluded development of effective treatments. ALS presents as a sporadic condition 90-95% of the time, i.e., without familial history or obvious genetic mutation. This suggests that ALS has a strong environmental component. Organophosphates (OPs) are prime candidate neurotoxicants in the etiology of ALS, as exposure to OPs was linked to higher ALS incidence among farmers, soccer players, and Gulf War veterans...
January 9, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28058446/hepatotoxic-effects-of-cyproconazole-and-prochloraz-in-wild-type-and-hcar-hpxr-mice
#19
Philip Marx-Stoelting, Katrin Ganzenberg, Constanze Knebel, Flavia Schmidt, Svenja Rieke, Helen Hammer, Felix Schmidt, Oliver Pötz, Michael Schwarz, Albert Braeuning
The agricultural fungicides cyproconazole and prochloraz exhibit hepatotoxicity in rodent studies and are tumorigenic following chronic exposure. Both substances are suspected to act via a CAR (constitutive androstane receptor)/PXR (pregnane-X-receptor)-dependent mechanism. Human relevance of these findings is under debate. A 28-day toxicity study was conducted in mice with humanized CAR and PXR (hCAR/hPXR) with two dose levels (50 or 500 ppm) of both substances, using the model CAR activator phenobarbital as a reference...
January 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28054104/inhalation-of-gas-metal-arc-stainless-steel-welding-fume-promotes-lung-tumorigenesis-in-a-j-mice
#20
Lauryn M Falcone, Aaron Erdely, Terence G Meighan, Lori A Battelli, Rebecca Salmen, Walter McKinney, Samuel Stone, Amy Cumpston, Jared Cumpston, Ronnee N Andrews, Michael Kashon, James M Antonini, Patti C Zeidler-Erdely
Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas metal arc-stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice...
January 4, 2017: Archives of Toxicology
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