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Toxicology Letters

J Keller, W Mellert, S Sperber, H Kamp, X Jiang, E Fabian, M Herold, T Walk, V Strauss, B van Ravenzwaay
For regulatory purposes prenatal developmental toxicity (OECD 414) studies are routinely performed in our laboratories. The suitability of metabolomics as technology to identify maternal toxicity in such studies was investigated. Plasma was sampled from pregnant, non-fasted rats on gestation day 20 before cesarean section. Metabolite profiling was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. The sensitivity of routinely examined maternal toxicity parameters (OECD No. 414) was compared to those of metabolome analysis...
November 8, 2018: Toxicology Letters
Zhe Jin, Miao Chi, Quan He, Yuanjiang Pan, Cuirong Sun
Perfluorooctane sulfonyl fluoride (PFOSF) has been defined as persistent organic pollutant in the Stockholm Convention in 2009. Currently PFOSF and its substitutes (structural analogues in which octyl group is substituted for other aliphatic chains) are still scarcely studied. HSA is a main carrier for drugs in blood, and the influence of exogenous compounds including pollutants on HSA is of particular interest. In this work, the binding sites of HSA to Perfluoroalkane sulfonyl fluoride (PFASFs) were determined by fluorescence technique...
November 5, 2018: Toxicology Letters
Meng Yang, Xinlai Qian, Na Wang, Yingying Ding, Haibin Li, Yingzheng Zhao, Sanqiao Yao
Epithelial-mesenchymal transition (EMT) is linked to fibrosis following exposure to silica. The scavenger receptor, macrophage receptor with collagenous structure (MARCO) plays an important role in silica-induced inflammation, however, the effect of MARCO on silica-induced fibrosis has not been identified. We hypothesized that MARCO regulates EMT and is required for the development of silicosis. Herein, we found that MARCO was highly expressed in lung tissue after exposure to silica and a MARCO inhibitor PolyG could alleviate pulmonary fibrosis in vivo...
October 31, 2018: Toxicology Letters
Somya Asthana, Sumita Dixit, Anshuman Srivastava, Arvind Kumar, Sheelendra P Singh, Anurag Tripathi, Mukul Das
Some districts of Bihar, especially Muzzaffarpur district, have been known to be affected by annual outbreak, called locally as Acute Encephalitis Syndrome (AES) which became one of the major health concerns in Bihar, due to its high fatality and complications. Several hypotheses like bat virus, heat stroke, pesticide exposure and the presence of a compound - methylenecyclopropyl glycine (MCPG) in Litchi have been proposed by different investigators for AES. When the investigators examined the symptoms, signs and the epidemiological data, bat virus and heat stroke hypothesis were ruled out...
October 30, 2018: Toxicology Letters
Mohsen Rezaei, Elham Keshtzar, Mohammad Javad Khodayar, Mansoureh Javadipour
BACKGROUND: a large body of evidence indicates that accumulation of oxidative stress originated from impaired mitochondrial respiratory chain is the main cause for the development of numerous diseases including diabetes and cancer. Arsenic exposure is a potential risk factor for type 2 diabetes development which, by disrupting mitochondrial respiration and SirT3 enzyme activity, enhances reactive oxygen species (ROS) level and evokes oxidative stress. In this study the impact of arsenic exposure on the mitochondrial function and SirT3 from rat's liver were examined in the presence or absence of metformin and berberine...
October 29, 2018: Toxicology Letters
Feihai Shen, Zhewen Xiong, Jiamin Kong, Li Wang, Yisen Cheng, Jing Jin, Zhiying Huang
Triptolide (TP) is the main ingredient of Chinese herb Tripterygium wilfordii Hook f. (TWHF). Despite of its multifunction in pharmaceutics, accumulating evidences showed that TP caused obvious hepatotoxicity in clinic. The current study investigated the role of Notch1 signaling in TP-induced hepatotoxicity. Our data indicated that TP inhibited the protein expression of Notch1 and its active form Notch intracellular domain (NICD) leading to increased PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression...
October 28, 2018: Toxicology Letters
Toshihide Takeshita, Fumiya Tao, Nobuhiko Kojima, Robert A Kanaly
A DNA adduct screening pipeline was constructed to apply triple quadrupole mass spectrometry comparative DNA adductomics to investigate the effects of the naturally-occurring plant constituent, safrole (4-allyl-1,2-methylenedioxybenzene), on human hepatoma cells, Hep G2. DNA from Hep G2 cells that were exposed to or not exposed to safrole were digested to 2'-deoxynucleosides and analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) whereby the neutral loss of 2'-deoxyribose was targeted by monitoring the [M+H]+ > [M+H - 116]+ transition over a defined range...
October 28, 2018: Toxicology Letters
Bo Sun, Xiaobing Zhou, Zhe Qu, Li Sun, Guilin Cheng, Yanwei Yang, Yufa Miao, Xiaoguang Chen, Bo Li
Drug-induced acute kidney injury is a serious problem in drug development and clinical treatment. Thus, highly efficient and non-invasive urinary biomarkers are required to control and prevent drug-induced acute kidney injury. Expanding on a previous study, we evaluated 9 novel urinary biomarkers in beagles, which were treated with gentamycin at a dose of 40 mg/kg for 12 consecutive days. N-acetyl-β-D-glucosaminidase was detected with high sensitivity and specificity at the early stage of renal injury (Area under the ROC cure (AUC) = 0...
October 28, 2018: Toxicology Letters
Jingwen Guo, Zhifeng Yang, Qiang Jia, Cunxiang Bo, Hua Shao, Zhenling Zhang
To study the role of pirfenidone in rats exposed to silica dust, we established the rat silicosis model with 50 mg/ml silica by intratracheal instillation. From the first day after silica instillation, rats were given pirfenidone (50, 100 mg/kg/day) and rats were sacrificed at 14 days and 28 days to observe the histopathology of lungs, to analyze the level of TNF-α, IL-1β, IL-6 in lung tissues and to measure the expression of TGF-β1, Smad2/3, vimentin, and E-cadherin in lung tissues. Results showed that pirfenidone (50, 100 mg/kg/day) reduced the silica-induced alveolar inflammation, the damage of alveolar structure and the blue areas of collagen fibers in the lungs of rats...
October 28, 2018: Toxicology Letters
Tao Guan, Ke Huang, Yuanyuan Liu, Shihui Hou, Chengfang Hu, Yi Li, Jingbo Zhang, Jinghong Zhao, Jun Zhang, Rupeng Wang, Yunjian Huang
Robo1/Robo2-NCK1/NCK2 signaling pathway controls endothelial cell sprouting and migration induced by Slit2 or VEGF, but whether it is involved in peritubular capillary (PTC) rarefaction of Aristolochic acid nephropathy (AAN) is unclear. In the present study, we evaluated whether AA exerts antiangiogenic effects by targeting this signaling pathways in HUVECs. HUVECs or lentivirus-mediated NCK1-overexpressing HUVECs were stimulated with AA (1, 2 or 3 μg/ml) in the absence or presence of 6 nM Slit2. Our results showed that AAІ (1-3 μg/ml) dose-dependently inhibited the migration and tube formation of HUVECs...
October 28, 2018: Toxicology Letters
Tracey Hurrell, Kathryn S Lilley, Allan Duncan Cromarty
Despite the importance of hepatotoxicity testing in the development of new potential pharmaceuticals, standardized methods for preclinical in vitro hepatotoxicity is complicated by the perceived adequacy of approach, diversity of origin of cells, and the ability to retain a satisfactory hepatocellular phenotype. Additionally, the confidence with which cells mimic in vitro hepatocytes is dictated by the spatial dynamics of the cell culture microenvironment. This study sought to compare the proteome of conventional monolayer cultures of an immortalized hepatocyte cell line (HepG2) with more complex three-dimensional spheroid cultures to ascertain whether changes in culture technique better mimic the phenotype of hepatocytes and thereby improve responses to in vivo hepatotoxins...
October 28, 2018: Toxicology Letters
Sukanya Das, Scott D Smid
We investigated the effects of the small molecule flavorants diacetyl, 2,3-pentanedione and acetoin on neuronal cell viability and β amyloid aggregation and morphology. Two neuroblastoma cell lines, SH-SY5Y and Neuro 2a (N2a) were exposed to diacetyl, 2,3-pentanedione and acetoin, while Thioflavin T fluorescence kinetics and transmission electron microscopy were used to assess effects on Aβ1-42 fibril and aggregate formation and morphology respectively. Diacetyl was intrinsically toxic to both SH-SY5Y and N2a cells, with time and concentration-dependent reductions in cell viability occurring over 24 h and 48 h incubation periods...
October 28, 2018: Toxicology Letters
Longfei Du, Kai Shen, Ying Bai, Jie Chao, Gang Hu, Yuan Zhang, Honghong Yao
Nod-like Receptor Protein 3 (NLRP3) inflammasome activation is known to lead to microglia-mediated neuroinflammation. Methamphetamine is known to induce microglial activation. However, whether NLRP3 inflammasome activation contributes to the microglial activation induced by methamphetamine remains elusive. P53-up-regulated modulator of apoptosis (PUMA) is a known apoptosis inducer; however, their role in microglial activation remains poorly understood. Methamphetamine treatment induced NLRP3 inflammasome activation as well microglial activation in animal model...
October 27, 2018: Toxicology Letters
Fenglei Chen, Xin Wen, Pengfei Lin, Huatao Chen, Aihua Wang, Yaping Jin
HERP is an endoplasmic reticulum (ER) membrane protein and is strongly induced by stress conditions. A recent study has indicated that HERP cooperates in apoptosis during zearalenone (ZEA) treatment. However, regulatory mechanisms and the role of HERP in ZEA-induced apoptosis remain elusive in ovarian granulosa cells. In this study, MTT and flow cytometry assays demonstrated that ZEA gradually decreased cell viability and increased apoptosis in granulosa cells in a dose-dependent manner. Western blot analysis showed that ZEA significantly activated autophagy by upregulating LC3-II...
October 27, 2018: Toxicology Letters
Lucie Hyrsova, Alena Vanduchova, Jan Dusek, Tomas Smutny, Alejandro Carazo, Veronika Maresova, Frantisek Trejtnar, Pavel Barta, Pavel Anzenbacher, Zdenek Dvorak, Petr Pavek
Resveratrol (RSV) is a stilbene phytochemical common in food and red wine. RSV inhibits cytochrome P450 CYP3A4 activity and interacts with the pregnane X receptor (PXR), the central regulator of drug/xenobiotic metabolizing enzyme expression. In this work, we comprehensively examined the effects of 13 stilbenes (trans- and cis-resveratrol, trans- and cis-piceatannol, oxyresveratrol, pterostilbene, pinostilbene, a,b-dihydroresveratrol, trans- and cis-trismethoxyresveratrol, trans-3,4,5,4'-tetramethoxystilbene, trans-2,4,3',5'-tetramethoxystilbene, trans-4-methoxystilbene), on CYP3A4 and CYP2B6 mRNA induction, and on CYP3A4/5, CYP2C8/9/19, CYP2D6, CYP2A6, CYP2E1, CYP1A2 and CYP2B6 cytochrome P450 enzyme activities...
October 27, 2018: Toxicology Letters
Maeve Shannon, Jodie Wilson, Yuling Xie, Lisa Connolly
Monosodium glutamate (MSG) is a commonly used flavour enhancer in households, catering and food production. Recently it has been highlighted as a suspected dietary obesogen in epidemiological studies indicating a link between MSG consumption and weight gain. Additionally, animal studies have shown that MSG exposure has profound effects on sex steroid hormone levels and receptors; which have an important role in energy metabolism. However, the exact mechanism by which MSG exerts its effects has yet to be elucidated...
October 27, 2018: Toxicology Letters
Mauro Maniscalco, Debora Paris, Dominique Melck, Nunzio Chiariello, Fiorentino Di Napoli, Maurizio Manno, Ivo Iavicoli, Andrea Motta
Exhaled breath condensate (EBC) is a non-invasive biological matrix that allows easy access to the lung epithelial lining fluid. It can provide, for instance, useful biochemical information in workers following inhalatory exposure. Recently, nuclear magnetic resonance (NMR)-based metabolomics has been applied to EBC profiling to identify metabolic phenotypes ("metabotypes") of relevance in respiratory medicine. We aimed at verifying if NMR-based metabolomics of EBC, combined with statistical analysis, could find differences in metabolomic profiles between groups of subjects occupationally exposed to levels of airborne inhalable dust, phenol, formaldehyde and volatile organic compounds (VOCs) below regulatory limits...
October 22, 2018: Toxicology Letters
Huiying Hua, Manyun Dai, Yishuang Luo, Hante Lin, Gangming Xu, Xiaowei Hu, Liping Xu, Haoyue Zhang, Zhiyuan Tang, Liming Chang, Aiming Liu, Julin Yang
Cholestasis is one of the most challenging diseases to be treated in current hepatology. However little is known about the adaptation difference and the underlying mechanism between acute and chronic cholestasis. In this study, wild-type and Pparα-null mice were orally administered diet containing 0.05% ANIT to induce chronic cholestasis. Biochemistry, histopathology and serum metabolome analysis exhibited the similar toxic phenotype between wild-type and Pparα-null mice. Bile acid metabolism was strongly adapted in Pparα-null mice but not in wild-type mice...
October 21, 2018: Toxicology Letters
Salvador Dominguez, Mayra Gisel Flores-Montoya, Christina Sobin
Developmental lead (Pb) exposure alters brain function through mechanisms that are not yet understood. A previous study showed that early lead exposure reduced microglia number in the dentate gyrus region of the hippocampus. Given the critical role of microglia in brain development, it is important to determine whether these differences are unique to the dentate gyrus, or occur throughout the hippocampus. Unbiased stereology was used to quantify microglia mean cell body number in total hippocampus, and compare the proportion of microglia in the ventral vs...
October 20, 2018: Toxicology Letters
Hannes Puntscher, Svenja Hankele, Katharina Tillmann, Eva Attakpah, Dominik Braun, Mary-Liis Kütt, Giorgia Del Favero, Georg Aichinger, Gudrun Pahlke, Harald Höger, Doris Marko, Benedikt Warth
Alternaria mycotoxins frequently contaminate agricultural crops and may impact animal and human health. However, data on mammalian metabolism and potential biomarkers of exposure for human biomonitoring (HBM) are scarce. Here, we report the preliminary investigation with respect to metabolism and excretion of Alternaria toxins in Sprague Dawley rats. Four animals were housed in metabolic cages for 24 h after gavage administration of an Alternaria alternata culture extract containing ten known toxins. LC-MS/MS analysis of 17 Alternaria toxins in urine and fecal samples allowed to gain first insights regarding xenobiotic metabolism and excretion rates...
October 12, 2018: Toxicology Letters
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