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Toxicology

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https://www.readbyqxmd.com/read/28800886/corrigendum-to-towards-in-vitro-dt-dnt-testing-assaying-chemical-susceptibility-in-early-differentiating-nt2-cells-toxicology-338-2015-69-76
#1
Ann-Katrin Menzner, Sepideh Abolpour Mofrad, Oliver Friedrich, Daniel F Gilbert
No abstract text is available yet for this article.
August 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28789971/the-use-of-high-throughput-screening-techniques-to-evaluate-mitochondrial-toxicity
#2
Lauren P Wills
Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity...
August 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28789970/mitochondrial-fusion-fission-and-mitochondrial-toxicity
#3
Joel N Meyer, Tess C Leuthner, Anthony L Luz
Mitochondrial dynamics are regulated by two sets of opposed processes: mitochondrial fusion and fission, and mitochondrial biogenesis and degradation (including mitophagy), as well as processes such as intracellular transport. These processes maintain mitochondrial homeostasis, regulate mitochondrial form, volume and function, and are increasingly understood to be critical components of the cellular stress response. Mitochondrial dynamics vary based on developmental stage and age, cell type, environmental factors, and genetic background...
August 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28778750/ecological-significance-of-mitochondrial-toxicants
#4
Nishad Jayasundara
Mitochondrial dysfunction with exposure to anthropogenic contaminants is a critical concern in biomedical and ecological health. Importantly, understanding the role of mitotoxicants in modulating organismal fitness and survival, particularly in the context of species' resilience to shifts in abiotic factors with climate change, is emerging as a key consideration. To date, only a few studies have focused on effects of mitotoxicants on organismal responses to additional abiotic stressors (e.g., shifts in temperature, levels of oxygen, and salinity); however, these serve to demonstrate that chemical exposure could alter stress responses...
August 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28774668/chronic-exposure-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-induces-an-obesogenic-effect-in-c57bl-6j-mice-fed-a-high-fat-diet
#5
Axelle Brulport, Ludovic Le Corre, Marie-Christine Chagnon
Contaminant involvement in the pathophysiology of obesity is widely recognized. It has been shown that low dose and chronic exposure to endocrine disruptor compounds (EDCs) potentiated diet- induced obesity. High and acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant (POP) and an EDC with anti-estrogenic property, causes wasting syndrome . However at lower doses, the TCDD metabolic effects remain poorly understood. We investigated the obesogenic effect during chronic exposure of TCDD at 1μg/kg body weight (bw)/week in adult C57BL/6J mice fed with a high fat diet (HFD) and exposed from 10 to 42 weeks old to TCDD or equal volume of vehicle by intragastric gavage...
July 31, 2017: Toxicology
https://www.readbyqxmd.com/read/28774667/the-current-status-of-exposure-driven-approaches-for-chemical-safety-assessment-a-cross-sector-perspective
#6
REVIEW
Fiona Sewell, Manoj Aggarwal, Gerald Bachler, Alan Broadmeadow, Nichola Gellatly, Emma Moore, Sally Robinson, Martijn Rooseboom, Alexander Stevens, Claire Terry, Natalie Burden
For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible...
July 31, 2017: Toxicology
https://www.readbyqxmd.com/read/28765055/mitochondrial-dysfunction-as-a-trigger-of-innate-immune-responses-and-inflammation
#7
A Phillip West
A growing literature indicates that mitochondria are key participants in innate immune pathways, functioning as both signaling platforms and contributing to effector responses. In addition to regulating antiviral signaling and antibacterial immunity, mitochondria also are important drivers of inflammation caused by sterile injury. Much research on mitochondrial control of immunity now centers on understanding how mitochondrial constituents released during cellular damage simulate the innate immune system. When mitochondrial integrity is compromised, mitochondrial damage-associated molecular patterns engage pattern recognition receptors, trigger inflammation, and promote pathology in an expanding list of diseases...
July 29, 2017: Toxicology
https://www.readbyqxmd.com/read/28757096/clinical-effects-of-chemical-exposures-on-mitochondrial-function
#8
Zarazuela Zolkipli-Cunningham, Marni J Falk
Mitochondria are critical for the provision of ATP for cellular energy requirements. Tissue and organ functions are dependent on adequate ATP production, especially when energy demand is high. Mitochondria also play a role in a vast array of important biochemical pathways including apoptosis, generation and detoxification of reactive oxygen species, intracellular calcium regulation, steroid hormone and heme synthesis, and lipid metabolism. The complexity of mitochondrial structure and function facilitates its diverse roles but also enhances its vulnerability...
July 27, 2017: Toxicology
https://www.readbyqxmd.com/read/28756246/inherited-mitochondrial-genomic-instability-and-chemical-exposures
#9
Sherine S L Chan
There are approximately 1,500 proteins that are needed for mitochondrial structure and function, most of which are encoded in the nuclear genome (Calvo et al., 2006). Each mitochondrion has its own genome (mtDNA), which in humans encodes 13 polypeptides, 22 tRNAs and 2 rRNAs required for oxidative phosphorylation. The mitochondrial genome of humans and most vertebrates is approximately 16.5 kbp, double-stranded, circular, with few non-coding bases. Thus, maintaining mtDNA stability, that is, the ability of the cell to maintain adequate levels of mtDNA template for oxidative phosphorylation is essential and can be impacted by the level of mtDNA mutation currently within the cell or mitochondrion, but also from errors made during normal mtDNA replication, defects in mitochondrial quality control mechanisms, and exacerbated by exposures to exogenous and/or endogenous genotoxic agents...
July 26, 2017: Toxicology
https://www.readbyqxmd.com/read/28750850/mitochondria-targeting-by-environmental-stressors-implications-for-redox-cellular-signaling
#10
Chuck Blajszczak, Marcelo G Bonini
Mitochondria are cellular powerhouses as well as metabolic and signaling hubs regulating diverse cellular functions, from basic physiology to phenotypic fate determination. It is widely accepted that reactive oxygen species (ROS) generated in mitochondria participate in the regulation of cellular signaling, and that some mitochondria chronically operate at a high ROS baseline. However, it is not completely understood how mitochondria adapt to persistently high ROS states and to environmental stressors that disturb the redox balance...
July 24, 2017: Toxicology
https://www.readbyqxmd.com/read/28743514/precision-cut-lung-slices-as-test-system-for-candidate-therapeutics-in-organophosphate-poisoning
#11
Julia Herbert, Horst Thiermann, Franz Worek, Timo Wille
Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28743513/chronic-exposure-to-the-fungicide-propiconazole-behavioral-and-reproductive-evaluation-of-f1-and-f2-generations-of-male-rats
#12
Milene Leivas Vieira, Nathália Orlandini Costa, Marina Rangel F Pereira, Suzana de Fátima Paccola Mesquita, Estefânia Gastaldello Moreira, Daniela Cristina Ceccatto Gerardin
Several studies have suggested that propiconazole (PROP) may be an endocrine disruptor; possibly altering the activity of the CYP51 enzyme, which is part of the cholesterol biosynthesis pathway required for the production of sexual steroid hormones. Another PROP effect is inhibition of the aromatase enzyme that converts androgens into estrogens, which could lead to negative effects on reproductive parameters. Therefore, the present study evaluated the reproductive and developmental toxicity of PROP by exposing two generations (F1 and F2) of male rats to this fungicide, since a previous study from our lab reported that PROP has anti-estrogenic and anti-androgenic activities (Costa et al...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28743512/inferring-transcription-factor-activity-from-microarray-data-reveals-novel-targets-for-toxicological-investigations
#13
T M Souza, T van den Beucken, J C S Kleinjans, D G J Jennen
Transcription factors (TFs) are important modulators of the inducible portion of the transcriptome, and therefore relevant in the context of exposure to exogenous compounds. Current approaches to predict the activity of TFs in biological systems are usually restricted to a few entities at a time due to low-throughput techniques targeting a limited fraction of annotated human TFs. Therefore, high-throughput alternatives may help to identify new targets of mechanistic and predictive value in toxicological investigations...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28743511/raf-1-ck2-and-rhoa-rock-signaling-promote-tnf-%C3%AE-mediated-endothelial-apoptosis-via-regulating-vimentin-cytoskeleton
#14
Lifeng Yang, Lian Tang, Fan Dai, Guoliang Meng, Runting Yin, Xiaole Xu, Wenjuan Yao
Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28720507/formation-and-degradation-of-nitrogen-mustard-induced-mgmt-dna-crosslinking-in-16hbe-cells
#15
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
#16
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
#17
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
#18
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
#19
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
#20
Xin-Wei Dong, Yong-Liang Jia, Ling-Tian Ge, Bo Jiang, Jun-Xia Jiang, Jian Shen, Ya-Chao Jin, Yan Guan, 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 8, 2017: Toxicology
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