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Toxicology

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https://www.readbyqxmd.com/read/28720507/formation-and-degradation-of-nitrogen-mustard-induced-mgmt-dna-crosslinking-in-16hbe-cells
#1
Jin Cheng, Feng Ye, Guorong Dan, Yuanpeng Zhao, Jiqing Zhao, Zhongmin Zou
N-methyl-2,2-di(chloroethyl)amine (HN2) is a kind of bifunctional alkyltating agent, which can react with nucleophilic groups in DNA and/or protein to form HN2-bridged crosslinking of target molecules, such as DNA-protein crosslinkings (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme which solely repairs alkyl adduct on DNA directly. However, MGMT was detected to act as a protein cross-linked with DNA via alkylation in presence of HN2, and unexpectedly turned into a DNA damage enhancer in the form of MGMT-DNA cross-link (mDPC)...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28712647/perinatal-exposure-to-2-2-4-4-tetrabromodiphenyl-ether-induces-testicular-toxicity-in-adult-rats
#2
Ahmed Khalil, Mikhail Parker, Sarah E Brown, Sebnem E Cevik, Lian W Guo, Jake Jensen, Alexandra Olmsted, Daneal Portman, Haotian Wu, Alexander Suvorov
Since 1965, polybrominated diphenyl ethers (PBDEs) have been used internationally as flame-retardant additives. PBDEs were recently withdrawn from commerce in North America and Europe due to their environmental persistence, bioaccumulative properties and endocrine-disrupting effects. Generations exposed perinatally to the highest environmental doses of PBDE account for one-fifth of the total United States population. While, toxicity of PBDE for the male reproductive system has been demonstrated in several human and animal studies, the long-lasting effects of perinatal exposures on male reproduction are still poorly understood...
July 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28710020/nrf2-deficiency-exacerbates-ochratoxin-a-induced-toxicity-in-vitro-and-in-vivo
#3
Agnieszka Loboda, Anna Stachurska, Mateusz Sobczak, Paulina Podkalicka, Olga Mucha, Alicja Jozkowicz, Jozef Dulak
Several mechanisms are postulated to be responsible for nephrotoxic and nephrocarcinogenic activities of mycotoxin and food contaminant, ochratoxin A (OTA). Although Nrf2 transcription factor was suggested to be involved in OTA-mediated renal injury, comprehensive study evaluating the effect of OTA toxicity in Nrf2 knock-out mice with special regard to sex-dependency has not been performed yet. Our results clearly show exacerbated OTA toxicity in porcine tubular epithelial cells after shRNA-mediated Nrf2 inhibition as well as in proximal tubular cells isolated from Nrf2(-/-) male mice in comparison to cells derived from their wild-type counterparts...
July 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28710019/effects-of-human-blood-levels-of-two-pah-mixtures-on-the-ahr-signalling-activation-pathway-and-cyp1a1-and-comt-target-genes-in-granulosa-non-tumor-and-granulosa-tumor-cell-lines
#4
Karolina Zajda, Anna Ptak, Agnieszka Rak, Elżbieta Fiedor, Adam Grochowalski, Tomasz Milewicz, Ewa L Gregoraszczuk
Epidemiological studies have shown a link between problems with offspring of couples living in a contaminated environment in comparison to those who live in an uncontaminated environment. We measured the concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) in maternal and cord blood. To explore the mechanism of the effects of PAH mixtures on nonluteinized granulosa cells (HGrC1) and granulosa tumor cells (COV434), as well as cell proliferation and apoptosis, we investigated the effect of PAH mixtures on the expression of the aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and aryl hydrocarbon receptor repressor (AHRR) genes, as well as the expression and activity of target genes cytochrome P450 1A1 (CYP1A1) and catechol-O-methyltransferase (COMT)...
July 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28705778/maternal-linuron-exposure-alters-testicular-development-in-male-offspring-rats-at-the-whole-genome-level
#5
Jianwei Bai, Hua Han, Feng Wang, Liyu Su, Hongwei Ding, Xiyin Hu, Binli Hu, Hong Li, Wei Zheng, Yan Li
Linuron is a widely used herbicide; its toxicity on the male reproductive system has been recognized. The current study was designed to explore the molecular mechanism underlying linuron-induced reproductive toxicity. Pregnant rats received daily oral gavage of linuron at the dose of 120mg/kg/d from gestation day (GD)12 to GD17. Tissues from male offspring rats were collected for pathological examination and microarray gene expression profiling. Changes in gene expression were further verified by quantitative real-time RT-PCR...
July 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28694203/soluble-epoxide-hydrolase-inhibitor-auda-decreases-bleomycin-induced-pulmonary-toxicity-in-mice-by-inhibiting-the-p38-smad3-pathways
#6
Xin-Wei Dong, Yong-Liang Jia, Ling-Tian Ge, Bo Jiang, Jun-Xia Jiang, Shen Jian, Ya-Chao Jin, Guan Yan, Yun Sun, Qiang-Min Xie
Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-β1-induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways...
July 7, 2017: Toxicology
https://www.readbyqxmd.com/read/28689766/acute-administration-of-tramadol-and-tapentadol-at-effective-analgesic-and-maximum-tolerated-doses-causes-hepato-and-nephrotoxic-effects-in-wistar-rats
#7
Joana Barbosa, Juliana Faria, Sandra Leal, Luís Pedro Afonso, João Lobo, Odília Queirós, Roxana Moreira, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids...
July 6, 2017: Toxicology
https://www.readbyqxmd.com/read/28688903/differential-effects-between-developmental-and-postpubertal-exposure-to-n-methyl-n-nitrosourea-on-progenitor-cell-proliferation-of-rat-hippocampal-neurogenesis-in-relation-to-cox2-expression-in-granule-cells
#8
Yousuke Watanabe, Kota Nakajima, Sayaka Mizukami, Yumi Akahori, Nobuya Imatanaka, Gye-Hyeong Woo, Toshinori Yoshida, Makoto Shibutani
This study was performed to compare the exposure effects of N-methyl-N-nitrosourea (MNU), a cytocidal agent of proliferating cells, on rat hippocampal neurogenesis between developmental and postpubertal periods. Developmental exposure through maternal drinking water from gestational day 6 to day 21 after delivery on weaning decreased GFAP-immunoreactive ((+)) stem cells and increased immunoreactive cells indicative of subsequent progenitor and postmitotic immature neuronal populations, TUNEL(+) or p21(Cip1/Waf1+) stem/progenitor cells and COX2(+) granule cells, on postnatal day (PND) 21...
July 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28669868/questions-about-methodological-and-ethical-quality-of-a-vaccine-adjuvant-critical-paper
#9
LETTER
David Hawkes, Joanne Benhamu
No abstract text is available yet for this article.
June 29, 2017: Toxicology
https://www.readbyqxmd.com/read/28666936/human-induced-pluripotent-stem-cell-hipsc-derived-neurons-respond-to-convulsant-drugs-when-co-cultured-with-hipsc-derived-astrocytes
#10
Misawa Niki Ishii, Koji Yamamoto, Masanobu Shoji, Asano Asami, Yuji Kawamata
Accurate risk assessment for drug-induced seizure is expected to be performed before entering clinical studies because of its severity and fatal damage to drug development. Induced pluripotent stem cell (iPSC) technology has allowed the use of human neurons and glial cells in toxicology studies. Recently, several studies showed the advantage of co-culture system of human iPSC (hiPSC)-derived neurons with rodent/human primary astrocytes regarding neuronal functions. However, the application of hiPSC-derived neurons for seizure risk assessment has not yet been fully addressed, and not at all when co-cultured with hiPSC-derived astrocytes...
June 27, 2017: Toxicology
https://www.readbyqxmd.com/read/28655545/mitochondrial-dysfunction-in-glial-cells-implications-for-neuronal-homeostasis-and-survival
#11
Jordan Rose, Christian Brian, Jade Woods, Aglaia Pappa, Mihalis I Panayiotidis, Robert Powers, Rodrigo Franco
Mitochondrial dysfunction is central to the pathogenesis of neurological disorders. Neurons rely on oxidative phosphorylation to meet their energy requirements and thus alterations in mitochondrial function are linked to energy failure and neuronal cell death. Furthermore, dysfunctional mitochondria are reported to increase the steady-state levels of reactive oxygen species derived from the leakage of electrons from the electron transport chain. Research aimed at understanding mitochondrial dysfunction and its role in neurological disorders has been primarily geared towards neurons...
June 24, 2017: Toxicology
https://www.readbyqxmd.com/read/28655544/mitochondria-and-mitochondrial-dna-as-relevant-targets-for-environmental-contaminants
#12
Deborah A Roubicek, Nadja C de Souza-Pinto
The mitochondrial DNA (mtDNA) is a closed circular molecule that encodes, in humans, 13 polypeptides components of the oxidative phosphorylation complexes. Integrity of the mitochondrial genome is essential for mitochondrial function and cellular homeostasis, and mutations and deletions in the mtDNA lead to oxidative stress, mitochondrial dysfunction and cell death. In vitro and in situ studies suggest that when exposed to certain genotoxins, mtDNA accumulates more damage than nuclear DNA, likely owing to its organization and localization in the mitochondrial matrix, which tends to accumulate lipophilic, positively charged molecules...
June 24, 2017: Toxicology
https://www.readbyqxmd.com/read/28652195/predicting-drug-induced-liver-injury-the-importance-of-data-curation
#13
Eleni Kotsampasakou, Floriane Montanari, Gerhard F Ecker
Drug-induced liver injury (DILI) is a major issue for both patients and pharmaceutical industry due to insufficient means of prevention/prediction. In the current work we present a 2-class classification model for DILI, generated with Random Forest and 2D molecular descriptors on a dataset of 966 compounds. In addition, predicted transporter inhibition profiles were also included into the models. The initially compiled dataset of 1773 compounds was reduced via a 2-step approach to 966 compounds, resulting in a significant increase (p-value<0...
June 23, 2017: Toxicology
https://www.readbyqxmd.com/read/28645577/quantitative-structure-skin-permeability-relationships
#14
REVIEW
Ivanka Tsakovska, Ilza Pajeva, Merilin Al Sharif, Petko Alov, Elena Fioravanzo, Simona Kovarich, Andrew P Worth, Andrea-Nicole Richarz, Chihae Yang, Aleksandra Mostrag-Szlichtyng, Mark T D Cronin
This paper reviews in silico models currently available for the prediction of skin permeability. A comprehensive discussion on the developed methods is presented, focusing on quantitative structure-permeability relationships. In addition, the mechanistic models and comparative studies that analyse different models are discussed. Limitations and strengths of the different approaches are highlighted together with the emergent issues and perspectives.
June 21, 2017: Toxicology
https://www.readbyqxmd.com/read/28645579/anti-androgenic-mechanisms-of-bisphenol-a-involve-androgen-receptor-signaling-pathway
#15
Hui Wang, Zhen Ding, Qiao-Mei Shi, Xing Ge, Heng-Xue Wang, Meng-Xue Li, Gang Chen, Qi Wang, Qiang Ju, Jin-Peng Zhang, Mei-Rong Zhang, Li-Chun Xu
We have shown Bisphenol A (BPA) acts as an androgen receptor (AR) antagonist in the previous study. However, the mechanisms underlying anti-androgenic effects of BPA remain unclear. The objective of this study was to explore whether the AR signaling was involved in AR antagonism of BPA. The Cell Counting Kit-8 (CCK-8) assay and Real-Time Cell Analysis (RTCA) iCELLigence system were applied to analyze the mouse Sertoli cell TM4 proliferation. The mammalian two-hybrid assays were performed to investigate the effects of BPA on the AR amino- and carboxyl-terminal regions (N/C) interaction and the interactions of the AR with steroid receptor coactivator-1 (SRC-1), co-repressors including silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (NCoR)...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645578/the-electrophilic-character-of-quinones-is-essential-for-the-suppression-of-bach1
#16
Chuanyang Su, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important cellular defense mechanisms against oxidative attack. BTB and CNC homology-1 (Bach1), like Kelch-like ECH-associated protein 1 (Keap1), is one of a negative regulator of Nrf2 that control antioxidant response elements (ARE)-dependent gene expressions. In the current study, we found that quinones show greater capacity than hydroquinones in nuclear Bach1 export, as well as ubiquitin-dependent Bach1 degradation in our experimental time frame...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#17
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#18
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28627408/developmental-exposure-to-glyphosate-based-herbicide-and-depressive-like-behavior-in-adult-offspring-implication-of-glutamate-excitotoxicity-and-oxidative-stress
#19
Daiane Cattani, Patrícia Acordi Cesconetto, Mauren Kruger Tavares, Eduardo Benedetti Parisotto, Paulo Alexandre De Oliveira, Carla Elise Heinz Rieg, Marina Concli Leite, Rui Daniel Schröder Prediger, Nestor Cubas Wendt, Guilherme Razzera, Danilo Wilhelm Filho, Ariane Zamoner
We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats...
June 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28627407/sources-mechanisms-and-consequences-of-chemical-induced-mitochondrial-toxicity
#20
EDITORIAL
Joel N Meyer, Sherine S L Chan
No abstract text is available yet for this article.
June 13, 2017: Toxicology
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