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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/27913141/acute-lung-injury-and-persistent-small-airway-disease-in-a-rabbit-model-of-chlorine-inhalation
#1
Sadiatu Musah, Connie F Schlueter, David M Humphrey, Karen S Powell, Andrew M Roberts, Gary W Hoyle
Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed...
November 29, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27913140/comparative-analysis-of-tcdd-induced-ahr-mediated-gene-expression-in-human-mouse-and-rat-primary-b-cells
#2
Natalia Kovalova, Rance Nault, Robert Crawford, Timothy R Zacharewski, Norbert E Kaminski
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation...
November 29, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27899277/protective-role-of-hypoxia-inducible-factor-1%C3%AE-dependent-cd39-and-cd73-in-fulminant-acute-liver-failure
#3
Eunyoung Tak, Dong-Hwan Jung, Seok-Hwan Kim, Gil-Chun Park, Dae Young Jun, Jooyoung Lee, Bo-Hyun Jung, Varvara A Kirchner, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF...
November 27, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27899278/benznidazole-the-trypanocidal-drug-used-for-chagas-disease-induces-hepatic-nrf2-activation-and-attenuates-the-inflammatory-response-in-a-murine-model-of-sepsis
#4
Flavia Lambertucci, Omar Motiño, Silvina Villar, Juan Pablo Rigalli, María de Luján Alvarez, Viviana Catania, Paloma Martín-Sanz, Cristina Ester Carnovale, Ariel Darío Quiroga, Daniel Eleazar Francés, María Teresa Ronco
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear erythroid 2-related factor 2 (NRF2) in vitro...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27894914/the-unexpected-teratogenicity-of-rxr-antagonist-uvi3003-via-activation-of-ppar%C3%AE-in-xenopus-tropicalis
#5
Jingmin Zhu, Amanda Janesick, Lijiao Wu, Lingling Hu, Weiyi Tang, Bruce Blumberg, Huahong Shi
The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo)...
November 25, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27894913/the-regulation-of-cellular-apoptosis-by-the-ros-triggered-perk-eif2%C3%AE-chop-pathway-plays-a-vital-role-in-bisphenol-a-induced-male-reproductive-toxicity
#6
Li Yin, Yanlin Dai, Zhihong Cui, Xiao Jiang, Wenbin Liu, Fei Han, Ao Lin, Jia Cao, Jinyi Liu
Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate...
November 25, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27889531/sirt1-protects-cardiac-cells-against-apoptosis-induced-by-zearalenone-or-its-metabolites-%C3%AE-and-%C3%AE-zearalenol-through-an-autophagy-dependent-pathway
#7
Intidhar Ben Salem, Manel Boussabbeh, Julie Pires Da Silva, Arnaud Guilbert, Hassen Bacha, Salwa Abid-Essefi, Christophe Lemaire
Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). In the present study, we investigated the underlying mechanism of the toxicity induced by ZEN, α-ZOL and β-ZOL in cardiac cells (H9c2). We show that treatment with ZEN or its metabolites induces the activation of the mitochondrial pathway of apoptosis as characterized by an increase in ROS generation, a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspases...
November 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27888061/secretory-function-of-ovarian-cells-and-myometrial-contractions-in-cow-are-affected-by-chlorinated-insecticides-chlordane-heptachlor-mirex-in-vitro
#8
Michael Hubert Wrobel, Jaroslaw Mlynarczuk
The aim of the study was to investigate the effect of chlordane, heptachlor and mirex, on hormonal regulation of the force of myometrial contractions. Myometrial, endometrial, granulosa and luteal cells as well as strips of myometrium from non-pregnant cows were incubated with three insecticides at environmentally relevant doses (0.1, 1 or 10ng/ml). None of the insecticides affected the viability of studied cells. Chlordane stimulated, while heptachlor and mirex inhibited, secretion of testosterone and estradiol from granulosa cells as well as secretion of progesterone from luteal cells, respectively...
November 22, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27884602/a-data-driven-weighting-scheme-for-multivariate-phenotypic-endpoints-recapitulates-zebrafish-developmental-cascades
#9
Guozhu Zhang, Kyle R Roell, Lisa Truong, Robert L Tanguay, David M Reif
Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints...
November 21, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27871888/multidrug-and-toxin-extrusion-proteins-mediate-cellular-transport-of-cadmium
#10
Hong Yang, Dong Guo, Obinna N Obianom, Tong Su, James E Polli, Yan Shu
Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd(2+)). In this study, we aimed to examine whether Cd(2+) is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd(2+)...
November 18, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27871887/a-silk-peptide-fraction-restores-cognitive-function-in-af64a-induced-alzheimer-disease-model-rats-by-increasing-expression-of-choline-acetyltransferase-gene
#11
Yeseul Cha, Sang Hoon Lee, Su Kil Jang, Haiyu Guo, Young-Hwan Ban, Dongsun Park, Gwi Yeong Jang, Sungho Yeon, Jeong-Yong Lee, Ehn-Kyoung Choi, Seong Soo Joo, Heon-Sang Jeong, Yun-Bae Kim
This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction...
November 18, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27865854/obeticholic-acid-protects-against-carbon-tetrachloride-induced-acute-liver-injury-and-inflammation
#12
Da-Gang Zhang, Cheng Zhang, Jun-Xian Wang, Bi-Wei Wang, Hua Wang, Zhi-Hui Zhang, Yuan-Hua Chen, Yan Lu, Li Tao, Jian-Qing Wang, Xi Chen, De-Xiang Xu
The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl4)-induced acute liver injury. Mice were intraperitoneally injected with CCl4 (0.15ml/kg). In CCl4+OCA group, mice were orally with OCA (5mg/kg) 48, 24 and 1h before CCl4. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl4-induced elevation of serum ALT and hepatic necrosis...
November 16, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27851896/corrigendum-to-low-doses-of-arsenic-via-perturbing-p53-promotes-tumorigenesis-toxicol-appl-pharmacol-2016-98-104
#13
Suthakar Ganapathy, Ping Li, Johan Fagman, Tianqi Yu, Jean Lafontant, Guojun Zhang, Changyan Chen
No abstract text is available yet for this article.
November 13, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27847315/single-toxin-dose-response-models-revisited
#14
Eugene Demidenko, S P Glaholt, E Kyker-Snowman, J R Shaw, C Y Chen
The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate...
November 12, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27838152/sibutramine-provokes-apoptosis-of-aortic-endothelial-cells-through-altered-production-of-reactive-oxygen-and-nitrogen-species
#15
Yoshifumi Morikawa, Akinobu Shibata, Naoko Okumura, Akira Ikari, Yasuhide Sasajima, Koichi Suenami, Kiyohito Sato, Yuji Takekoshi, Ossama El-Kabbani, Toshiyuki Matsunaga
Overdose administration of sibutramine, a serotonin-noradrenalin reuptake inhibitor, is considered to elicit severe side effects including hypertension, whose pathogenic mechanism remains unclear. Here, we found that 48-h incubation with >10μM sibutramine provokes apoptosis of human aortic endothelial (HAE) cells. Treatment with the lethal concentration of sibutramine facilitated production of reactive oxygen species (ROS), altered expression of endoplasmic reticulum stress response genes (heat shock protein 70 and C/EBP homologous protein), and inactivated 26S proteasome-based proteolysis...
November 9, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27818216/estimation-of-iodine-nutrition-and-thyroid-function-status-in-late-gestation-pregnant-women-in-the-united-states-development-and-application-of-a-population-based-pregnancy-model
#16
A Lumen, N I George
Previously, a deterministic biologically-based dose-response (BBDR) pregnancy model was developed to evaluate moderate thyroid axis disturbances with and without thyroid-active chemical exposure in a near-term pregnant woman and fetus. In the current study, the existing BBDR model was adapted to include a wider functional range of iodine nutrition, including more severe iodine deficiency conditions, and to incorporate empirically the effects of homeostatic mechanisms. The extended model was further developed into a population-based model and was constructed using a Monte Carlo-based probabilistic framework...
November 3, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27746315/trpa1-mediates-changes-in-heart-rate-variability-and-cardiac-mechanical-function-in-mice-exposed-to-acrolein
#17
Nicole Kurhanewicz, Rachel McIntosh-Kastrinsky, Haiyan Tong, Allen Ledbetter, Leon Walsh, Aimen Farraj, Mehdi Hazari
Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone...
October 13, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27746314/carvedilol-suppresses-circulating-and-hepatic-il-6-responsible-for-hepatocarcinogenesis-of-chronically-damaged-liver-in-rats
#18
Mohamed Balaha, Samah Kandeel, Waleed Barakat
Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin...
October 13, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27743861/udca-and-cdca-alleviate-17%C3%AE-ethinylestradiol-induced-cholestasis-through-pka-ampk-pathways-in-rats
#19
Xiaojiaoyang Li, Zihang Yuan, Runping Liu, Hozeifa M Hassan, Hang Yang, Rong Sun, Luyong Zhang, Zhenzhou Jiang
Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model...
October 12, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27720938/identification-of-gene-expression-profiling-associated-with-erlotinib-related-skin-toxicity-in-pancreatic-adenocarcinoma-patients
#20
Octavio Caba, Antonio Irigoyen, Cristina Jimenez-Luna, Manuel Benavides, Francisco M Ortuño, Javier Gallego, Ignacio Rojas, Carmen Guillen-Ponce, Carolina Torres, Enrique Aranda, Jose Prados
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients...
October 6, 2016: Toxicology and Applied Pharmacology
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