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Toxicology

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https://www.readbyqxmd.com/read/28323003/pulsed-or-continuous-electromagnetic-field-induce-p53-p21-mediated-apoptotic-signaling-pathway-in-mouse-spermatogenic-cells-in-vitro-and-thus-may-affect-male-fertility
#1
Przemyslaw Solek, Lena Majchrowicz, Dominika Bloniarz, Ewelina Krotoszynska, Marek Koziorowski
The impact of electromagnetic field (EMF) on the human health and surrounding environment is a common topic investigated over the years. A significant increase in the electromagnetic field concentration arouses public concern about the long-term effects of EMF on living organisms associated with many aspects. In the present study, we investigated the effects of pulsed and continuous electromagnetic field (PEMF/CEMF) on mouse spermatogenic cell lines (GC-1 spg and GC-2 spd) in terms of cellular and biochemical features in vitro...
March 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28315714/cadmium-induced-malignant-transformation-of-rat-liver-cells-potential-key-role-and-regulatory-mechanism-of-altered-apolipoprotein-e-expression-in-enhanced-invasiveness
#2
Masayo Suzuki, Shuso Takeda, Noriko Teraoka-Nishitani, Akane Yamagata, Takahiro Tanaka, Marika Sasaki, Natsuki Yasuda, Makiko Oda, Tatsuji Okano, Kazuhiro Yamahira, Yuta Nakamura, Takanobu Kobayashi, Katsuhito Kino, Hiroshi Miyazawa, Michael P Waalkes, Masufumi Takiguchi
Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity. Our prior studies have utilized a rat liver epithelial cell line (TRL 1215) as a model for cadmium-induced malignant transformation...
March 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28315715/sab-mediates-mitochondrial-dysfunction-involved-in-imatinib-mesylate-induced-cardiotoxicity
#3
Tara P Chambers, Luis Santiesteban, David Gomez, Jeremy W Chambers
Imatinib mesylate is an effective treatment for chronic myelogenous leukemia and gastrointestinal stromal tumors. Although imatinib mesylate is highly tolerable, it has been implicated in severe congestive heart failure in mouse models and patients. A hallmark of imatinib mesylate-induced cardiotoxicity is mitochondrial dysfunction. The mitochondrial scaffold Sab has been implicated in facilitating signaling responsible for mitochondrial dysfunction in a c-Jun N-terminal Kinase (JNK)-dependent manner. We examined the impact of Sab-mediated signaling on imatinib mesylate cardiotoxicity in H9c2 rat cardiomyocyte-like cells...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28315349/diethylstilbestrol-induces-oxidative-dna-damage-resulting-in-apoptosis-of-spermatogonial-stem-cells-in-vitro
#4
Khaled Habas, Martin H Brinkworth, Diana Anderson
The spermatogonial stem cells (SSCs) are the only germline stem cells in adults that are responsible for the transmission of genetic information from mammals to the next generation. SSCs play a very important role in the maintenance of progression of spermatogenesis and help provide an understanding of the reproductive biology of future gametes and a strategy for diagnosis and treatment of infertility and male reproductive toxicity. Androgens/oestrogens are very important for the suitable maintenance of male germ cells...
March 14, 2017: Toxicology
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#5
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28288858/the-margin-of-internal-exposure-moie-concept-for-dermal-risk-assessment-based-on-oral-toxicity-data-a-case-study-with-caffeine
#6
Jos G M Bessems, Alicia Paini, Monika Gajewska, Andrew Worth
Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28286206/simplified-qpcr-method-for-detecting-excessive-mtdna-damage-induced-by-exogenous-factors
#7
Artem P Gureev, Ekaterina A Shaforostova, Anatoly A Starkov, Vasily N Popov
Damage to mitochondrial DNA (mtDNA) is a meaningful biomarker for evaluating genotoxicity of drugs and environmental toxins. Existing PCR methods utilize long mtDNA fragments (∼8-10kb), which complicates detecting exact sites of mtDNA damage. To identify the mtDNA regions most susceptible to damage, we have developed and validated a set of primers to amplify ∼2kb long fragments, while covering over 95% of mouse mtDNA. We have modified the detection method by greatly increasing the enrichment of mtDNA, which allows us solving the problem of non-specific primer annealing to nuclear DNA...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28286205/ochratoxin-a-induced-premature-senescence-in-human-renal-proximal-tubular-cells
#8
Xuan Yang, Sheng Liu, Chuchu Huang, Haomiao Wang, Yunbo Luo, Wentao Xu, Kunlun Huang
Ochratoxin A (OTA) has many nephrotoxic effects and is a promising compound for the study of nephrotoxicity. Human renal proximal tubular cells (HKC) are an important model for the study of renal reabsorption, renal physiology and pathology. Since the induction of OTA in renal senescence is largely unknown, whether OTA can induce renal senescence, especially at a sublethal dose, and the mechanism of OTA toxicity remain unclear. In our study, a sublethal dose of OTA led to an enhanced senescent phenotype, β-galactosidase staining and senescence associated secretory phenotype (SASP)...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28286204/long-term-acetaminophen-treatment-induced-liver-fibrosis-in-mice-and-the-involvement-of-egr-1
#9
Qingyun Bai, Hongyu Yan, Yuchen Sheng, Yao Jin, Liang Shi, Lili Ji, Zhengtao Wang
Acetaminophen (APAP)-induced acute liver injury has already been well studied. However, whether long-term administration of APAP will cause liver fibrosis is still not very clear. This study aims to investigate the liver fibrosis in mice induced by long-term APAP treatment and the involvement of early growth response 1 (Egr-1). C57BL/6 mice were orally given with APAP (200, 300mg/kg) for 2, 6 or 10 weeks, respectively. Liver hydroxyproline content, collagen deposition and inflammatory cells infiltration were increased in mice treated with APAP (200, 300mg/kg) for 6 or 10 weeks...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28285101/comparative-toxicity-of-mono-and-bifunctional-alkylating-homologues-of-sulphur-mustard-in-human-skin-keratinocytes
#10
Thomas W Sawyer, Karin McNeely, Kristen Louis, Pierre Lecavalier, Yanfeng Song, Mercy Villanueva, Robin Clewley
Sulphur mustard (bis(2-chloroethyl) sulphide; agent H) is a vesicant chemical warfare (CW) agent whose mechanism of action is not known with any certainty and for which there are no effective antidotes. It has a pronounced latent period before signs and symptoms of poisoning appear which it shares with the nitrogen mustards, and that differentiates it from other classes of vesicant agents. Sulphur mustard, the sulphur mustard CW agents Q (1,2-bis(2-chloroethylthio) ethane) and T (1,1 bis(2-chloroethylthioethyl) ether), the H partial hydrolysis product hemi-sulphur mustard (2-chloroethyl 2-hydroxyethyl sulphide; HSM), and the commercially available 2-chloroethyl ethyl sulphide (CEES) were characterized with respect to their toxicity in first passage cultures of proliferating human skin keratinocytes, the target cell of H-induced skin vesication...
March 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28285100/engineering-epithelial-stromal-interactions-in-vitro-for-toxicology-assessment
#11
REVIEW
David G Belair, Barbara D Abbott
Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance...
March 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28285099/mir-1247-blocks-sox9-mediated-regeneration-in-alcohol-and-fibrosis-associated-acute-kidney-injury-in-mice
#12
Kostiantyn Dreval, Aline de Conti, Shinji Furuya, Frederick A Beland, Ivan Rusyn, Igor P Pogribny
Excessive alcohol consumption has a significant impact on human health and is a major public health problem worldwide. One of the consequences of long-term excessive alcohol consumption is cellular injury in almost all organs and tissues, with acute kidney injury (AKI) being one of the most common pathological manifestations. In the present study, using a mouse model of alcoholic liver fibrosis-associated AKI induced by a combined treatment with carbon tetrachloride (CCl4) and ethanol and resembling pathological features of AKI in human alcoholic liver fibrosis, we demonstrate alterations in histone modifications in the kidneys and, importantly, in the promoter region of the over-expressed SRY (sex determining region Y)-box 9 (Sox9) gene...
March 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28274658/effects-of-different-base-agents-on-prediction-of-skin-irritation-by-sodium-lauryl-sulfate-using-patch-testing-and-repeated-application-test
#13
Kotomi Horita, Daisuke Horita, Hiroyuki Tomita, Mitsue Yasoshima, Akiko Yagami, Kayoko Matsunaga
Animal testing for cosmetics was banned in the European Union (EU) in 2013; therefore, human tests to predict and ensure skin safety such as the patch test or usage test are now in demand in Japan as well as in the EU. In order to investigate the effects of different bases on the findings of tests to predict skin irritation, we performed patch testing (PT) and the repeated application test (RAT) using sodium lauryl sulfate (SLS), a well-known irritant, dissolved in 6 different base agents to examine the effects of these bases on skin irritation by SLS...
March 6, 2017: Toxicology
https://www.readbyqxmd.com/read/28267586/maternal-carbamazepine-alters-fetal-neuroendocrine-cytokines-axis
#14
R G Ahmed
This study detected the effects of maternal carbamazepine (CBZ) on the fetal neuroendocrine-cytokines axis. 25 or 50mg/kg of CBZ was intraperitoneally administrated to pregnant rats from gestation day (GD) 1 to 20. In dams and their fetuses, there was an elevation in the values of serum thyrotropin (TSH) which was accompanied by a decrease in the values of serum thyroxine (T4) and triiodothyronine (T3) at GD 20 due to both maternal administrations of CBZ compared to the control group. Also, both administrations had undesirable impacts on the maternal body weight gain, fetal body weight, survival of dams and fetuses, food consumption, and litter weight as compared to the corresponding control group...
March 3, 2017: Toxicology
https://www.readbyqxmd.com/read/28263783/establishment-of-a-novel-mouse-model-for-pioglitazone-induced-skeletal-muscle-injury
#15
Sho Akai, Shingo Oda, Tsuyoshi Yokoi
Skeletal muscle (SKM) injury is one of the major safety concerns in risk assessment for drug development. However, no appropriate pre-clinical animal model exists to evaluate drug-induced SKM injury except that caused by fibrates and statins. Thiazolidinedione, a PPARγ agonistic drug for type 2 diabetes mellitus, is widely used clinically but can induce adverse effects such as hepatotoxicity and SKM injury, as has been reported in recent decades. Moreover, thiazolidinedione-induced SKM injury has only been reported in humans, and no evidence of SKM injury has been observed in rodents...
March 2, 2017: Toxicology
https://www.readbyqxmd.com/read/28232124/models-of-toxicity-of-diacetyl-and-alternative-diones
#16
David M Brass, Scott M Palmer
Diacetyl (DA; 2,3-butanedione), with the chemical formula (CH3CO)2 is a volatile organic compound with a deep yellow color and a strong buttery flavor and aroma. These properties have made DA a particularly useful and common food flavoring ingredient. However, because of this increased occupational use, workers can be exposed to high vapor concentrations in the workplace. Despite being listed by the USFDA to be 'generally regarded as safe' (GRAS), multiple lines of evidence suggest that exposure to high concentrations of DA vapor causes long-term impairments in lung function with lung function testing indicating evidence of either restrictive or obstructive airway narrowing in affected individuals...
February 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28212817/in-vivo-toxicity-of-copper-oxide-lead-oxide-and-zinc-oxide-nanoparticles-acting-in-different-combinations-and-its-attenuation-with-a-complex-of-innocuous-bio-protectors
#17
Ilzira A Minigalieva, Boris A Katsnelson, Vladimir G Panov, Larisa I Privalova, Anatoly N Varaksin, Vladimir B Gurvich, Marina P Sutunkova, Vladimir Ya Shur, Ekaterina V Shishkina, Irene E Valamina, Ilya V Zubarev, Oleg H Makeyev, Ekaterina Y Meshtcheryakova, Svetlana V Klinova
Stable suspensions of metal oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure copper, zinc or lead under a layer of deionized water were used separately, in three binary combinations and a triple combination in two independent experiments on rats. In one of the experiments the rats were instilled with Me-NPs intratracheally (i.t.) (for performing a broncho-alveolar lavage in 24h to estimate the cytological and biochemical indices of the response of the lower airways), while in the other, Me-NPs were repeatedly injected intraperitoneally (i...
February 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28202386/paraquat-and-maneb-co-exposure-induces-noradrenergic-locus-coeruleus-neurodegeneration-through-nadph-oxidase-mediated-microglial-activation
#18
Liyan Hou, Cong Zhang, Ke Wang, Xiaofang Liu, Hongwei Wang, Yuning Che, Fuqiang Sun, Xueying Zhou, Xiulan Zhao, Qingshan Wang
Co-exposure to paraquat (PQ) and maneb (Mb) has been shown to increase the risk of Parkinson's disease (PD) and dopaminergic (DA) neurodegeneration in the substantia nigra pars compacta (SNpc) is observed in PQ and Mb-treated experimental animals. The loss of noradrenergic locus coeruleus (LC/NE) neurons in brainstem is a common feature shared by multiple neurodegenerative diseases, including PD. However, whether PQ and Mb is able to damage LC/NE neurons remains undefined. In this study, mice treated with combined PQ and Mb displayed progressive LC/NE neurodegeneration...
February 13, 2017: Toxicology
https://www.readbyqxmd.com/read/28202387/varenicline-enhances-oxidized-ldl-uptake-by-increasing-expression-of-lox-1-and-cd36-scavenger-receptors-through-%C3%AE-7-nachr-in-macrophages
#19
Yuki Kanaoka, Mitsuhisa Koga, Keita Sugiyama, Kaoru Ohishi, Yasufumi Kataoka, Atsushi Yamauchi
Varenicline is a widely used and effective drug for smoking cessation. It is a partial agonist of the α4β2 nicotinic acetylcholine receptor (nAChR) and full agonist of α7 nAChR. We have reported that varenicline aggravates formation of atherosclerotic plaques through α7 nAChR in apolipoprotein E knockout mice. However, little is known about its effects on macrophages in atherosclerotic plaques. Here, we ascertained whether varenicline promotes oxidized low-density lipoprotein (oxLDL) uptake in mouse peritoneal macrophages in vitro and clarified its mechanism...
February 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28189721/1-2-dichloroethane-impairs-glucose-and-lipid-homeostasis-in-the-livers-of-nih-swiss-mice
#20
Ting Wang, Dandan Xu, Qiming Fan, Weifeng Rong, Jiewei Zheng, Chen Gao, Guoliang Li, Ni Zeng, Tao Guo, Lihai Zeng, Fei Wang, Chen Xiao, Li Cai, Shangqing Tang, Xinlei Deng, Xiao Yin, Manqi Huang, Fengrong Lu, Qiansheng Hu, Wen Chen, Zhenlie Huang, Qing Wang
Excessive exposure to 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to liver dysfunction. To fully explore the mechanism of 1,2-DCE-induced hepatic abnormalities, 30 male National Institutes of Health (NIH) Swiss mice were exposed to 0, 350, or 700mg/m(3) of 1,2-DCE, via inhalation, 6h/day for 28days. Increased liver/body weight ratios, as well as serum AST and serum ALT activity were observed in the 350 and 700mg/m(3) 1,2-DCE exposure group mice, compared with the control group mice...
February 8, 2017: Toxicology
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