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Chloé Reymond, Nina Jaffré, Nicolas Taudon, Mathilde Menneteau, Hervé Chaussard, Josiane Denis, Cédric Castellarin, Franck Dhote, Frédéric Dorandeu
Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope ®), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate (AVZ). While this treatment is effective against several of the known nerve agents, it shows little efficacy against the Russian VX (VR), one of the most toxic compounds...
September 12, 2018: Toxicology
Yongsoon Kim, Jaeseong Jeong, Jisu Yang, Sang-Woo Joo, Jongki Hong, Jinhee Choi
Graphene oxide (GO) has the potential for wide applications, which necessitates an intensive investigation of its potential hazard on human and environmental health. Even if previous studies show reproductive toxicity in the nematode Caenorhabditis elegans, the mechanisms of reproductive toxicity by GO are poorly understood. To understand the underlying mechanisms of GO-induced reproductive toxicity, we investigated the interaction between GO and C. elegans using Raman spectroscopy, sperm counts produced by spermatogenesis, progeny and analyzed the fatty acid metabolism using molecular techniques...
September 12, 2018: Toxicology
Boxuan Liang, Yizhou Zhong, Kengkeng Chen, Lihai Zeng, Guoliang Li, Jiewei Zheng, Liang Jiang, Zhiwei Xie, Bingling Que, Guanchao Lai, Banghua Wu, Xingfen Yang, Jieling Wu, Yongmei Xiao, Wen Chen, Zhenlie Huang
Exposure to low-dose benzene may lead to hematotoxicity and cause health problems. Though peripheral blood cell count is widely used in benzene exposure assessment and health risk assessment, the reports regarding the effects of low-dose benzene exposure on blood cell count remain inconsistent. To uncover more sensitive biomarkers for low-dose benzene exposure, our previous study screened out three potential serum proteins-plasminogen (PLG), platelet basic protein (PBP) and apolipoprotein B100 (ApoB100)-as biomarkers from chronic benzene poisoning patients by using proteomic analysis...
September 10, 2018: Toxicology
Jung-Mou Yang, Huei-Mei Huang, Jing-Jy Cheng, Chuen-Lin Huang, Yi-Chao Lee, Chun-Tang Chiou, Hung-Tse Huang, Nai-Kuei Huang, Ying-Chen Yang
Paraquat (PQ) as an herbicide has been demonstrated to impair dopaminergic (DAergic) neurons and highly correlate with the etiology of Parkinson's disease (PD). WNT/β-CATENIN signaling is known for the specification and neurogenesis of midbrain DAergic neurons and implicated as a therapeutic target in treating many diseases, such as cancer and degenerative diseases. LGK974, a WNT pathway inhibitor, is currently under clinical trial for patients with malignancies. Since the exact role of WNT/β-CATENIN signaling in mediating PD is undetermined, LGK974 was used to examine its effect on the PQ-induced cell model of PD...
September 8, 2018: Toxicology
Chunteng Jiang, Liping Jiang, Qiannan Li, Xiaofang Liu, Tianjiao Zhang, Linlin Dong, Tiehong Liu, Li Liu, Guoling Hu, Xiance Sun, Lijie Jiang
Acrolein is a common environmental pollutant that has been linked to cardiovascular diseases, such as atherosclerosis (AS). Increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms haven't been completely elucidated. In human umbilical vein endothelial cells (HUVECs), we observed that acrolein treatment induced cell reactive oxygen species (ROS) generation, autophagy, pyroptosis and reduced cell migration. In addition, exposure to acrolein resulted in NLRP3 inflammasome activation as evidenced by cleavage of caspase-1 and downstream mature interleukin (IL)-1β and IL-18 secretion...
September 8, 2018: Toxicology
Jorge Estévez, Mónica Benabent, Verónica Selva, Iris Mangas, Miguel Ángel Sogorb, Eva Del Rio, Eugenio Vilanova
Some effects of organophosphorus compounds (OPs) esters cannot be explained by action on currently recognized targets acetylcholinesterase or neuropathy target esterase (NTE). In previous studies, in membrane chicken brain fractions, four components (EPα, EPβ, EPγ and EPδ) of phenyl valerate esterase activity (PVase) had been kinetically discriminated combining data of several inhibitors (paraoxon, mipafox, PMSF). EPγ is belonging to NTE. The relationship of PVase components and acetylcholine-hydrolyzing activity (cholinesterase activity) is studied herein...
August 31, 2018: Toxicology
Xiuli Zhang, Mengmeng Ji, Xuemei Tan, Kailun Yu, Xiaozhuan Liu, Ning Li, Zengli Yu
2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD) exposure in utero had been shown to affect ovarian development and functions. However, its mechanism remained unknown. In this study, to investigate the effect of maternal exposure to TCDD on ovaries, the pregnant Sprague Dawley (SD) rats were treated with TCDD (100 ng/kg or 500 ng/kg) or only vehicle and corn oil on the day 8-14 of gestation through the gavage with a stainless-steel feeding needle (once a day). The vaginal opening and estrous cycle of female offspring rats (F1) were monitored twice a day...
August 31, 2018: Toxicology
Liana M Matson, Robyn B Lee-Stubbs, C Lin Cadieux, Jeffrey A Koenig, Cherish E Ardinger, Jessica Chandler, Erik A Johnson, Heidi M Hoard-Fruchey, Tsung-Ming A Shih, Doug M Cerasoli, John H McDonough
Genetics likely play a role in various responses to nerve agent (NA) exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses. This study uses different mouse strains to identify if mouse strain differences in sarin exposure exist. In Experiment 1, basal levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CE) were measured in different strains of naïve mice to account for potential pharmacokinetic determinants of individual differences...
August 30, 2018: Toxicology
Lerin R Luckett-Chastain, Jenny R Gipson, Allison F Gillaspy, Randle M Gallucci
BACKGROUND: Irritant contact dermatitis (ICD) is a cutaneous inflammatory response to a variety of triggers that requires no sensitization and accounts for up to 80% of occupational dermatitis cases. IL-6 has been alternately associated with both allergic and irritant dermatitis and is closely linked to skin wound healing, therefore making it an ideal candidate to investigate in the mechanism of ICD. RESULTS: Despite being a well-known pro-inflammatory cytokine, IL-6 deficient (IL-6KO) mice show much more severe ICD than controls...
August 29, 2018: Toxicology
Zhixiang Xu, Bin Huang, Jun Liu, Xinhao Wu, Nao Luo, Xiaoxia Wang, Xianyao Zheng, Xuejun Pan
Breast cancer is the most diagnosed diseases and the second-leading cause of death in females, among which the estrogen receptor positive (ER+) patients are more common of all cases. In present study, we selected MCF-7 as an in vitro model and investigated the combinatorial anti-proliferative effects of tamoxifen and naringenin on ER+ breast cancer, and then explored the potential mechanisms involved in mitochondrial dysfunction and oxidative stress mediated by several estrogen receptor subtypes. Six assessment endpoints including cell viability, cell migration, cell cycle, cell apoptosis, mRNA, and protein expression were estimated...
August 25, 2018: Toxicology
Narendra P Singh, Kathryn Miranda, Udai P Singh, Prakash Nagarkatti, Mitzi Nagarkatti
Diethylstilbestrol (DES) is an endocrine disruptor that was used to prevent adverse effects of pregnancy in women in late 1940s until early 1970s. Its use was banned following significant toxicity and negative effects not only in the mothers but also transgenerationally. Previous studies from our laboratory showed that DES induces thymic atrophy and immunosuppression in mice. In this study, we investigated the molecular mechanisms through which DES triggers thymic atrophy, specifically autophagy. To that end, we treated C57BL/6 mice with DES, and determined expression of two autophagy-related proteins, microtubule-associated protein-1 light chain 3 (LC3) and Beclin-1 (Becn1)...
August 25, 2018: Toxicology
Qi-Yu Yang, Xiao-Dan Lai, Jing Ouyang, Jia-Dan Yang
BACKGROUND: Ginsenoside Rg3 (Rg3) is one of the key components of a frequently used herbal tonic panax ginseng for fatigue treatment. However, the molecular mechanisms of Rg3 on anti-fatigue effects have not been completely understood yet. METHODS AND MATERIALS: We built a postoperative fatigue syndrome (POFS) model and tried to elucidate the molecular mechanisms responsible for anti-fatigue effects of Rg3. 160 aged male rats were randomly divided into four groups (n = 40/group): normal group, Rg3-treated normal group (Rg3 group), postoperative fatigue syndrome model group (POFS group) and Rg3-treated postoperative fatigue syndrome model group (POFS + Rg3 group)...
August 23, 2018: Toxicology
Zuzana Šefčíková, Janka Babeľová, Štefan Čikoš, Veronika Kovaříková, Ján Burkuš, Alexandra Špirková, Juraj Koppel, Dušan Fabian
In this study the possible toxicity of phenylpyrazole fipronil, the related commercial product FIPRON spot-on as well as FIPRON spot-on secondary ingredients on the developmental capacities and quality of mouse preimplantation embryos was evaluated. During in vitro tests, isolated two-cell stage embryos were cultured in media with addition of the listed chemicals until blastocyst formation. Stereomicroscopic evaluation of in vitro produced embryos showed that fipronil at 1 μM and higher concentration negatively affected embryonic development...
August 18, 2018: Toxicology
Jingwen Chen, Qiang Niu, Tao Xia, Guoyu Zhou, Pei Li, Qian Zhao, Chunyan Xu, Lixin Dong, Shun Zhang, Aiguo Wang
Excessive exposure to fluoride has adverse effects on neurodevelopment, but the mechanisms remain unclear. This study aimed to investigate the effects of fluoride exposure on synaptogenesis, and focused on the role of brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling in these effects. Using Sprague-Dawley rats developmentally exposed to sodium fluoride (NaF) from pregnancy until 6 months of delivery as in vivo model, we showed that fluoride impaired the cognitive abilities of offspring rats, decreased the density of dendritic spines and the expression of synapse proteins synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) in hippocampus, suggesting fluoride-induced cognitive deficit associates with synaptic impairment...
August 18, 2018: Toxicology
Xilin Li, Zemin Wang, James E Klaunig
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western countries. The histological spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Nuclear receptors are a large group of ligand-dependent transcription factors that sense the environmental and endogenous changes and regulate numerous physiological and pathological processes. Accumulating evidence has suggested that a dysregulation of nuclear receptors in NAFLD may effect on the metabolism of endogenous and exogenous chemicals in the liver...
August 16, 2018: Toxicology
Zana A Carver, Alice A Han, Charles Timchalk, Thomas J Weber, Kimberly J Tyrrell, Ryan L Sontag, Teresa Luders, William B Chrisler, Karl K Weitz, Jordan N Smith
The objective of this study was to evaluate the potential for non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva. Using an in vitro rat salivary gland epithelial cell (SGEC) system, a collection of experiments investigating chemical protein binding, temporal and directional transport, as well as competitive transport with para-aminohippuric acid (PAH), a substrate for renal organic anion transporters, was conducted to identify cellular transport parameters required to computationally model salivary transport of 2,4-D...
August 16, 2018: Toxicology
Yutian Tian, Cengceng Chen, Shuhan Guo, Li Zhao, Yongjian Yan
OBJECTIVE: We explored methods to establish an animal model of manganese poisoning and evaluate the feasibility of the determination method. METHODS: Twenty-four specific pathogen-free male rats were randomly divided into four groups: control, low-dose (15.0 mg/kg), middle-dose (25.0 mg/kg), and high-dose (50.0 mg/kg). Intraperitoneal injection of MnCl2 ·H2 O was administered every 48 h for three months. Rats were tested for behavior, muscle tension, and with a balance beam experiment at the end of each month...
August 15, 2018: Toxicology
Katia Sayyed, Marc Le Vée, Hala Chamieh, Olivier Fardel, Ziad Abdel-Razzak
In animals, cigarette smoke may alter pharmacokinetics by altering activity and expression of ABC drug transporters. We previously demonstrated that cigarette smoke condensate (CSC) impairs activity and expression of several hepatic ABC drug transporters which mediate toxicant efflux. However, CSC effects on efflux transporters are still unknown in Saccharomyces cerevisiae which resists diverse chemical stresses, by inducing pleiotropic drug resistance (PDR) genes among others. The yeast ABC transporters are functionally and structurally homologous to the mammalian ones...
August 15, 2018: Toxicology
Hui Tao, Chen Dai, Ji-Fei Ding, Jing-Jing Yang, Xuan-Sheng Ding, Sheng-Song Xu, Kai-Hu Shi
Modulation of epigenetic marks has promised efficacy for treating fibrosis. Cardiac fibroblast is the primary source of activated myofibroblasts that produce extracellular matrix (ECM) in cardiac fibrosis, but the mechanisms underlying this process are incompletely understood. Here we show that microRNA-369-5p (miR-369-5p) through DNMT3A hypermethylation and suppression of the Patched1 pathway leads to fibroblast proliferation in cardiac fibrosis. Forty adult male Sprague-Dawley (SD) rats were randomly divided into two groups (sham and AAC group), cardiac fibrosis was produced by abdominal aortic constriction, and the operation of abdominal aortic constriction was carried out according to the method described...
August 14, 2018: Toxicology
Mariana A Ribeiro, Molly S Estill, Geysson J Fernandez, Leonardo N Moraes, Stephen A Krawetz, Wellerson R Scarano
Male fertility and spermatogenesis are directly linked to the Sertoli cell's ability to produce factors associated with germ cell development. Sertoli cells express receptors for FSH and testosterone, and are the major regulators of spermatogenesis. Recent studies report that regulatory RNA molecules, such as microRNAs (miRNAs), are able to modulate testicular function during spermatogenesis and that their altered expression may be involved in male infertility. miRNAs may play a role in the response to xenobiotics that have an adverse consequences to health...
August 7, 2018: Toxicology
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