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Toxicology

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https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#1
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10 days...
May 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28529061/benzo-a-pyrene-7-8-diol-9-10-epoxide-suppresses-the-migration-and-invasion-of-human-extravillous-trophoblast-htr-8-svneo-cells-by-down-regulating-mmp2-through-inhibition-of-fak-src-pi3k-akt-pathway
#2
Rong Wang, Weiping Wang, Lin Ao, Zhi Wang, Xianglin Hao, Huidong Zhang
Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0μM BPDE for 24h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0...
May 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28528174/prenatal-exposure-to-di-n-butyl-phthalate-disrupts-the-development-of-adult-leydig-cells-in-male-rats-during-puberty
#3
Xiaomin Chen, Linxi Li, Huitao Li, Hongguo Guan, Yaoyao Dong, Xiaoheng Li, Qiufan Wang, Qingquan Lian, Guoxin Hu, Ren-Shan Ge
Fetal exposure to di-n-butyl phthalate (DBP) causes the adult disease such as lower testosterone production and infertility. However, the mechanism is still unknown. The objective of the present study is to determine how DBP affects the involution of fetal Leydig cells during the neonatal period and how this event causes the delayed development of the adult Leydig cells during puberty. The pregnant Sprague Dawley dams were randomly divided into 3 groups and were gavaged with 0 (corn oil, the vehicle control), 100 or 500mg/kg DBP from gestational day 12 (G12) to G21...
May 17, 2017: Toxicology
https://www.readbyqxmd.com/read/28526321/effects-of-dehp-and-its-metabolite-mehp-on-insulin-signalling-and-proteins-involved-in-glut4-translocation-in-cultured-l6-myotubes
#4
Mangala Priya Viswanathan, Vigneswari Mullainadhan, Mayilvanan Chinnaiyan, Balasubramanian Karundevi
Di-(2-ethylhexyl)phthalate (DEHP) is the plasticizer used in variety of medical and consumer products to impart structural flexibility. DEHP and its primary metabolite mono-(2-ethyl hexyl)phthalate (MEHP) posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. Experimental and epidemiological data have shown that DEHP affects blood glucose homeostasis. However, direct effect of DEHP and its metabolite MEHP on insulin signal transduction and glucose transporter 4 (GLUT4) translocation remain obscure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28526320/mercury-exposure-induces-cytoskeleton-disruption-and-loss-of-renal-function-through-epigenetic-modulation-of-mmp9-expression
#5
Hafizurrahman Khan, Radha Dutt Singh, Ratnakar Tiwari, Siddhartha Gangopadhyay, Somendu Kumar Roy, Dhirendra Singh, Vikas Srivastava
Mercury is one of the major heavy metal pollutants occurring in elemental, inorganic and organic forms. Due to ban on most inorganic mercury containing products, human exposure to mercury generally occurs as methylmercury (MeHg) by consumption of contaminated fish and other sea food. Animal and epidemiological studies indicate that MeHg affects neural and renal function. Our study is focused on nephrotoxic potential of MeHg. In this study, we have shown for the first time how MeHg could epigenetically modulate matrix metalloproteinase 9(MMP9) to promote nephrotoxicity using an animal model of sub chronic MeHg exposure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28526319/lncrna-gas5-controls-cardiac-fibroblast-activation-and-fibrosis-by-targeting-mir-21-via-pten-mmp-2-signaling-pathway
#6
Hui Tao, Jia-Gui Zhang, Run-He Qin, Chen Dai, Peng Shi, Jing-Jing Yang, Zi-Yu Deng, Kai-Hu Shi
Long noncoding RNAs (LncRNAs) are aberrantly expressed in many diseases including cardiac fibrosis. LncRNA growth arrest-specific 5 (GAS5) is reported as a significant mediator in the control of cell proliferation and growth; however, the role and function in cardiac fibrosis remain unknown. In this study, we confirmed that GAS5 was lowly expressed in cardiac fibrosis tissues as well as activated cardiac fibroblast. Overexpression of GAS5 inhibited the proliferation of cardiac fibroblast. Moreover, microRNA-21 (miR-21) has been reported to be overexpressed in cardiac fibrosis tissues as well as activated cardiac fibroblast, which is responsible for the progression of cardiac fibrosis...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28499616/effective-analgesic-doses-of-tramadol-or-tapentadol-induce-brain-lung-and-heart-toxicity-in-wistar-rats
#7
Juliana Faria, Joana Barbosa, Sandra Leal, Luís Pedro Afonso, João Lobo, Roxana Moreira, Odília Queirós, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively)...
May 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28495607/prenatal-exposure-to-lambda-cyhalothrin-alters-brain-dopaminegric-signalling-in-developing-rats
#8
Yogesh K Dhuriya, Pranay Srivastava, Rajendra K Shukla, Richa Gupta, Dhirendra Singh, Devendra Parmar, Aditya B Pant, Vinay K Khanna
The present study is focused to decipher the molecular mechanisms associated with dopaminergic alterations in corpus striatum of developing rats exposed prenatally to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There was no significant change in the mRNA and protein expression of DA-D1 receptors at any of the doses of LCT (0.5, 1 & 3mg/kg body weight) in corpus striatum of developing rats exposed prenatally to LCT on PD22 & PD45. Prenatal exposure to LCT (1 & 3mg/kg body weight) resulted to decrease the level of mRNA and protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as compared to controls...
May 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28495606/the-synthetic-cannabinoid-win-55-212-55-212-induced-apoptosis-in-cytotrophoblasts-cells-by-a-mechanism-dependent-on-cb1-receptor
#9
Marta Almada, Lia Costa, Bruno Miguel Fonseca, Cristina Amaral, Natércia Teixeira, Georgina Correia-da-Silva
The endocannabinoid system has evolved as a key regulator in several pathological and physiological processes, including placentation, decidualization and implantation. In addition, it is known that Cannabis and cannabinoids negatively affect female reproduction. Although, the biological action of synthetic cannabinoids, such as WIN-55,212, in human fertility and pregnancy outcome remain to be unveiled. A tight balance between proliferation, differentiation and apoptosis of trophoblast cells is required for placental development and pregnancy outcome...
May 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28483492/dexamethasone-induces-human-glutathione-s-transferase-alpha-1-hgsta1-expression-through-the-activation-of-glucocorticoid-receptor-hgr
#10
Carmen Martínez-Guzmán, Pedro Cortés-Reynosa, Eduardo Pérez-Salazar, Guillermo Elizondo
The glutathione S transferases (GSTs) are a superfamily of isoenzymes that play an important role in xenobiotic and endobiotic detoxification, cellular protection from oxidative stress and modulation of signalling pathways. Human GSTA1 (hGSTA1), a cytosolic isoform, is the most abundant GST in the liver and is involved in the metabolism of carcinogenic compounds, chemotherapeutic agents and lipid peroxidation products. However, the molecular mechanism underlying the regulation of hGSTA1 expression is not well understood...
May 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28478275/identifying-environmental-chemicals-as-agonists-of-the-androgen-receptor-by-using-a-quantitative-high-throughput-screening-platform
#11
Caitlin Lynch, Srilatha Sakamuru, Ruili Huang, Diana A Stavreva, Lyuba Varticovski, Gordon L Hager, Richard S Judson, Keith A Houck, Nicole C Kleinstreuer, Warren Casey, Richard S Paules, Anton Simeonov, Menghang Xia
The androgen receptor (AR, NR3C4) is a nuclear receptor whose main function is acting as a transcription factor regulating gene expression for male sexual development and maintaining accessory sexual organ function. It is also a necessary component of female fertility by affecting the functionality of ovarian follicles and ovulation. Pathological processes involving AR include Kennedy's disease and Klinefelter's syndrome, as well as prostate, ovarian, and testicular cancer. Strict regulation of sex hormone signaling is required for normal reproductive organ development and function...
May 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28472626/key-role-of-oxidative-stress-in-animal-models-of-aminoglycoside-nephrotoxicity-revealed-by-a-systematic-analysis-of-the-antioxidant-to-nephroprotective-correlation
#12
Alfredo G Casanova, Laura Vicente-Vicente, María Teresa Hernández-Sánchez, Moisés Pescador, Marta Prieto, Carlos Martínez-Salgado, Ana I Morales, Francisco J López-Hernández
The clinical utility of aminoglycoside antibiotics is partly limited by their nephrotoxicity. Co-administration of a variety of candidate nephroprotectants has been tested at the preclinical level. According to a recent meta-analytic study, antioxidants are the only family of compounds with enough preclinical documentation to draw solid conclusions on their class nephroprotective capacity in animal models. In this study a systematic analysis of the relation between the level of antioxidation and the level of nephroprotection was performed...
May 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28458013/aberrant-methylation-of-runx3-is-present-in-aflatoxin-b1-induced-transformation-of-the-l02r-cell-line
#13
Shan Wang, Zhini He, Daochuan Li, Bo Zhang, Miao Li, Wenxue Li, Wei Zhu, Xiumei Xing, Xiaowen Zeng, Qing Wang, Guanghui Dong, Yongmei Xiao, Wen Chen, Liping Chen
Chronic exposure to aflatoxin B1 (AFB1) is linked to the development of hepatocellular carcinoma (HCC). To identify differentially methylated genes involved in AFB1-induced cell transformation, we analyzed DNA methylation patterns in immortal human hepatocyte L02 cells expressing an oncogenic H-Ras allele (L02R cells) and AFB1-transformed L02R (L02RT-AFB1) cells by performing genome-wide methylation profiling. We treated L02R cells with 0.3μM AFB1 weekly and observed a transformed phenotype at the 17th week post-treatment...
April 27, 2017: Toxicology
https://www.readbyqxmd.com/read/28454766/mixture-effects-of-azole-fungicides-on-the-adrenal-gland-in-a-broad-dose-range
#14
S Rieke, T Heise, F Schmidt, W Haider, H Bednarz, K Niehaus, A Mentz, J Kalinowski, K I Hirsch-Ernst, P Steinberg, L Niemann, P Marx-Stoelting
Consumers are exposed to low concentrations of a variety of pesticide residues in or on food. Some of them might interfere with the endocrine system. While each individual active substance has been extensively tested for toxicity and safety, potential combination effects possibly resulting from combined exposure to different pesticides have seldomly been tested so far, especially in vivo. Since the adrenal gland is a key endocrine organ, we investigated if and how substances of a group of fungicides presumed to interfere with the biosynthesis of steroid hormones affect this organ when applied individually and in combination in a broad dose range...
April 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28450064/a-paradoxical-response-of-the-rat-organism-to-long-term-inhalation-of-silica-containing-submicron-predominantly-nanoscale-particles-of-a-collected-industrial-aerosol-at-realistic-exposure-levels
#15
Marina P Sutunkova, Svetlana N Solovyeva, Boris A Katsnelson, Vladimir B Gurvich, Larisa I Privalova, Ilzira A Minigalieva, Tatyana V Slyshkina, Irene E Valamina, Oleg H Makeyev, Vladimir Ya Shur, Ilya V Zubarev, Dmitry K Kuznetsov, Ekaterina V Shishkina
While engineered SiO2 nanoparticle toxicity is being widely investigated, mostly on cell lines or in acute animal experiments, the practical importance of as well as the theoretical interest in industrial condensation aerosols with a high SiO2 particle content seems to be neglected. That is why, to the best of our knowledge, long-term inhalation exposure to nano-SiO2 has not been undertaken in experimental nanotoxicology studies. To correct this data gap, female white rats were exposed for 3 or 6 months 5 times a week, 4h a day to an aerosol containing predominantly submicron (nanoscale included) particles of amorphous silica at an exposure concentration of 2...
April 24, 2017: Toxicology
https://www.readbyqxmd.com/read/28434983/future-perspective-of-butter-flavorings-related-occupational-lung-disease
#16
EDITORIAL
Kendall B Wallace
No abstract text is available yet for this article.
April 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28433638/metabolomic-analysis-for-combined-hepatotoxicity-of-chlorpyrifos-and-cadmium-in-rats
#17
Ming-Yuan Xu, Pan Wang, Ying-Jian Sun, Yi-Jun Wu
Pesticides and heavy metals are widespread environmental pollutants. Although the acute toxicity of organophosphorus pesticide chlorpyrifos (CPF) and toxic heavy metal cadmium (Cd) is well characterized, the combined toxicity of CPF and Cd, especially the hepatotoxicity of the two chemicals with long-term exposure at a low dose, remained unclear. In this study, we investigated the toxicity in the liver of rats upon subchronic exposure to CPF and Cd at environmentally relevant doses. Rats were given three different doses (1/135 LD50, 1/45 LD50 and 1/15 LD50) of CPF and Cd as well as their mixtures by oral gavage for 90days...
April 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28412278/disruption-of-glutamate-neurotransmitter-transmission-is-modulated-by-snap-25-in-benzo-a-pyrene-induced-neurotoxic-effects
#18
Kai Yang, Xuejun Jiang, Qiuping Su, Jing Wang, Chunlin Li, Yinyin Xia, Shuqun Cheng, Qizhong Qin, Xianqing Cao, Chengzhi Chen, Baijie Tu
Benzo[a]pyrene (B[a]P), a ubiquitous chemical contaminant in the environment, is a well-established neurotoxicant to human. However, the molecular mechanisms for B[a]P neurotoxicity are still unclear. In the present study, after treating Sprague-Dawley rats with 0.02, 0.2 and 2.0mg/kg/day B[a]P for 7 weeks [from postnatal day (PND) 5 to PND54], our results showed that B[a]P exposure caused a significant deficits in learning and memory function. By using U87 cells as in vitro model, the significant cytotoxicity and the induction of apoptosis caused by B[a]P were further verified...
April 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28427893/study-of-acetylcholinesterase-activity-and-apoptosis-in-sh-sy5y-cells-and-mice-exposed-to-ethanol
#19
Wenjun Sun, Liangjing Chen, Wei Zheng, Xiaoan Wei, Wenqi Wu, Ellen G Duysen, Wei Jiang
Ethanol is one of the most commonly abused psychotropic substances with deleterious effects on the central nervous system. Ethanol exposure during development results in the loss of neurons in brain regions and when exposed to ethanol cultured cells undergo apoptosis. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals exposed to ethanol. The aims of the present study were to determine whether induction of AChE activity is associated with ethanol-induced apoptosis and to explore the mechanism of enhanced AChE activity induced by ethanol...
April 17, 2017: Toxicology
https://www.readbyqxmd.com/read/28395993/salinomycin-attenuates-liver-cancer-stem-cell-motility-by-enhancing-cell-stiffness-and-increasing-f-actin-formation-via-the-fak-erk1-2-signalling-pathway
#20
Jinghui Sun, Qing Luo, Lingling Liu, Xianjiong Yang, Shunqin Zhu, Guanbin Song
Salinomycin has recently been identified as an antitumour drug for several types of cancer stem cell (CSC) treatments. However, the effects of salinomycin on the migratory and invasive properties of liver cancer stem cells (LCSCs) are unclear. In present study, we investigated the effect of salinomycin on the migration and invasion of LCSCs, and examined the molecular mechanisms underlying the anticancer effects of salinomycin. Here we showed that the migration and invasion of LCSCs were significantly suppressed in a salinomycin dose-dependent manner...
April 8, 2017: Toxicology
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