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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/28807765/sglt2-inhibitor-and-dpp-4-inhibitor-improve-brain-function-via-attenuating-mitochondrial-dysfunction-insulin-resistance-inflammation-and-apoptosis-in-hfd-induced-obese-rats
#1
Piangkwan Sa-Nguanmoo, Pongpan Tanajak, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn
Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks...
August 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28807764/staphylococcal-enterotoxin-c2-mutant-drives-t-lymphocyte-activation-through-pi3k-mtor-and-nf-%C3%A4-b-signaling-pathways
#2
Xuanhe Fu, Mingkai Xu, Songyuan Yao, Huiwen Zhang, Chenggang Zhang, Jinghai Zhang
Staphylococcal enterotoxin C2 (SEC2), a superantigen, causes rapid clonal expansion of lymphocytes and secretion of T cell growth factors, leading to a severe inflammatory response within tissues. Although previous studies have shown that ST-4, a SEC2 mutant with enhanced recognition of Vβ regions of T-cell receptors (TCRVβ), can activate an increased number of T cells and produce more cytokines than SEC2. However, the signaling mechanisms of SEC2/ST-4-mediated immune activation have not been addressed. In this study, we showed that the phosphatidylinositide-3-kinase (PI-3K) inhibitor LY294002, mammalian target of rapamycin (mTOR) inhibitor rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor Bay11-7085 could suppress SEC2/ST-4-induced proliferation, CD69/CD25 expression, cell-cycle progression, and IL-2 production in BALB/c mouse splenocytes...
August 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28807763/effects-of-2-2-4-4-tetrabromodiphenyl-ether-on-neurobehavior-and-memory-change-and-bcl-2-c-fos-grin1b-and-lingo1b-gene-expression-in-male-zebrafish-danio-rerio
#3
Shukai Zheng, Caixia Liu, Yanhong Huang, Mian Bao, Yuanni Huang, Kusheng Wu
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants in various environmental matrices and organisms and pose a threat to neural systems of organisms. However, though quite a few studies have explored the effect of PBDEs on neural behaviors such as learning and memory abilities in animals, their mechanisms are less known. We used the zebrafish model to evaluate neurotoxicity of PBDEs and observe changes in behavior and related gene expression. In behavioral testing, 50 zebrafish were divided into five groups treated with different concentrations of BDE-47...
August 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803991/dhea-increases-epithelial-markers-and-decreases-mesenchymal-proteins-in-breast-cancer-cells-and-reduces-xenograft-growth
#4
Zaira Colín-Val, Viridiana Yazmín González-Puertos, Criselda Mendoza-Milla, Erika Olivia Gómez, Claudia Huesca-Gómez, Rebeca López-Marure
Breast cancer is one of the most common neoplasias and the leading cause of cancer death in women worldwide. Its high mortality rate is linked to a great metastatic capacity associated with the epithelial-mesenchymal transition (EMT). During this process, a decrease in epithelial proteins expression and an increase of mesenchymal proteins are observed. On the other hand, it has been shown that dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, inhibits migration of breast cancer cells; however, the underlying mechanisms have not been elucidated...
August 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803990/high-doses-of-baicalin-induces-kidney-injury-and-fibrosis-through-regulating-tgf-%C3%AE-smad-signaling-pathway
#5
Yi Cai, Wanqing Ma, Yichuan Xiao, Bo Wu, Xiaobing Li, Fengrong Liu, Jianhua Qiu, Genshui Zhang
Baicalin is a major flavonoid compound purified from Scutellariae radix, which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600mg/kg/day) induced significantly kidney injury and fibrosis...
August 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28782507/mapk-jnk1-activation-protects-cells-against-cadmium-induced-autophagic-cell-death-via-differential-regulation-of-catalase-and-heme-oxygenase-1-in-oral-cancer-cells
#6
Keum-Young So, Sang-Hun Kim, Ki-Tae Jung, Hyun-Young Lee, Seon-Hee Oh
Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy...
August 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28780372/species-specific-effects-of-neuregulin-1%C3%AE-cimaglermin-alfa-on-glucose-handling-in-animal-models-and-humans-with-heart-failure
#7
Zhihong Huang, Douglas B Sawyer, Erika L Troy, Corissa McEwen, John H Cleator, Abigail Murphy, Anthony O Caggiano, Andrew Eisen, Tom J Parry
Neuregulin-1β is a member of the neuregulin family of growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1β, cimaglermin alfa (also known as glial growth factor 2 or GGF2) is being investigated as a possible therapy for heart failure. Previous studies suggest that neuregulin-1β stimulation of skeletal muscle increases glucose uptake and, specifically, sufficient doses of cimaglermin alfa acutely produce hypoglycemia in pigs...
August 2, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28760446/in-vitro-to-in-vivo-extrapolation-of-effective-dosimetry-in-developmental-toxicity-testing-application-of-a-generic-pbk-modelling-approach
#8
Styliani Fragki, Aldert H Piersma, Emiel Rorije, Marco J Zeilmaker
Incorporation of kinetics to quantitative in vitro to in vivo extrapolations (QIVIVE) is a key step for the realization of a non-animal testing paradigm, in the sphere of regulatory toxicology. The use of Physiologically-Based Kinetic (PBK) modelling for determining systemic doses of chemicals at the target site is accepted to be an indispensable element for such purposes. Nonetheless, PBK models are usually designed for a single or a group of compounds and are considered demanding, with respect to experimental data needed for model parameterization...
July 28, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28755861/high-serum-lead-concentration-in-the-first-trimester-is-associated-with-an-elevated-risk-of-small-for-gestational-age-infants
#9
Hua Wang, Jun Li, Jia-Hu Hao, Yuan-Hua Chen, Lu Liu, Zhen Yu, Lin Fu, Fang-Biao Tao, De-Xiang Xu
A recent study found that gestational serum Pb concentration is associated with an increased risk of preterm birth. The purpose of this study was to analyze whether gestational Pb exposure elevates risk of small-for-gestational-age (SGA) births in a Chinese population. In the present study, total 3125 mother-infant pairs were recruited from the China-Anhui Birth Cohort Study (C-ABCS). Pb concentration in maternal serum was detected by GFAAS. All subjects were classified into three groups according to the tertile division of serum Pb concentration: L-Pb (low-Pb, <1...
July 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28755860/dynamic-and-accurate-assessment-of-acetaminophen-induced-hepatotoxicity-by-integrated-photoacoustic-imaging-and-mechanistic-biomarkers-in-vivo
#10
Nathalie Brillant, Mohamed Elmasry, Neal C Burton, Josep Monne Rodriguez, Jack W Sharkey, Stephen Fenwick, Harish Poptani, Neil R Kitteringham, Christopher E Goldring, Anja Kipar, B Kevin Park, Daniel J Antoine
The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention...
July 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28754437/inactivation-of-the-orphan-nuclear-receptor-nr4a1-contributes-to-apoptosis-induction-by-fangchinoline-in-pancreatic-cancer-cells
#11
Hyo-Seon Lee, Stephen Safe, Syng-Ook Lee
Previous studies have demonstrated that the orphan nuclear receptor NR4A1 is overexpressed in human pancreatic cancer and antagonizing this receptor promotes apoptosis and inhibits pancreatic cancer cells and tumor growth. In the present study, we identified fangchinoline, a bisbenzyltetrahydroisoquinoline alkaloid from Stephania tetrandra, as a new inactivator of nuclear NR4A1 and demonstrated that fangchinoline inhibits cell proliferation and induces apoptosis, in part, via the NR4A1-dependent pro-apoptotic pathways in human pancreatic cancer cells...
July 25, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28750898/the-use-of-a-unique-co-culture-model-of-fetoplacental-steroidogenesis-as-a-screening-tool-for-endocrine-disruptors-the-effects-of-neonicotinoids-on-aromatase-activity-and-hormone-production
#12
Elyse Caron-Beaudoin, Rachel Viau, Andrée-Anne Hudon-Thibeault, Cathy Vaillancourt, J Thomas Sanderson
Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid...
July 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28736076/suppression-of-ige-mediated-mast-cell-activation-and-mouse-anaphylaxis-via-inhibition-of-syk-activation-by-8-formyl-7-hydroxy-4-methylcoumarin-4%C3%AE-8c
#13
Seung Taek Nam, Young Hwan Park, Hyun Woo Kim, Hyuk Soon Kim, Dajeong Lee, Min Bum Lee, Young Mi Kim, Wahn Soo Choi
Mast cells trigger IgE-mediated allergic reactions by releasing various allergic mediators. 8-Formyl-7-hydroxy-4-methylcoumarin, also called 4μ8C, was originally known as an inositol-requiring enzyme 1 (IRE1) suppressant, but no study has examined its relationship with mast cells and allergic diseases. Therefore, the purpose of this study was to determine whether 4μ8C is effective in suppressing allergic reactions in mast cells and in IgE-mediated allergic animal model. 4μ8C suppressed the degranulation of IgE-mediated mast cells (IC50=3...
July 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28734801/sex-specific-differences-in-the-modulation-of-growth-differentiation-factor-15-gdf15-by-hyperoxia-in-vivo-and-in-vitro-role-of-hif-1%C3%AE
#14
Yuhao Zhang, Weiwu Jiang, Lihua Wang, Krithika Lingappan
Male premature neonates are more susceptible than females to the development of bronchopulmonary dysplasia (BPD). The reasons underlying sexually dimorphic outcomes in premature neonates are not known. GDF15 (Growth and differentiation factor 15) is a secreted cytokine and plays a role in cell proliferation, apoptosis, and angiogenesis. In this study, we sought to elucidate the sex-specific expression of Gdf15 in the lung in vivo in neonatal hyperoxic lung injury and its regulation by Hif-1α, and to delineate the differences in GDF15 expression in male and female human umbilical venous endothelial cells in an in vitro model of oxygen toxicity...
July 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733207/uplc-q-tof-ms-based-urine-and-plasma-metabonomics-study-on-the-ameliorative-effects-of-aspirin-eugenol-ester-in-hyperlipidemia-rats
#15
Ning Ma, Xi-Wang Liu, Xiao-Jun Kong, Zhe Qin, Shi-Hong Li, Zeng-Hua Jiao, Peng-Cheng Dong, Ya-Jun Yang, Jian-Yong Li
The main objective of this study was to investigate the ameliorative effects of aspirin eugenol ester (AEE) in hyperlipidemic rat. After five-week oral administration of AEE in high fat diet (HFD)-induced hyperlipidemic rats, the impact of AEE on plasma and urine metabonomics was investigated to explore the underlying mechanism by UPLC-Q-TOF/MS analysis. Blood lipid levels and histopathological changes of liver, stomach and duodenum were also evaluated after AEE treatment. Without obvious gastrointestinal (GI) side effects, AEE significantly relieved fatty degeneration of liver and reduced triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (P<0...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733206/omics-based-identification-of-the-combined-effects-of-idiosyncratic-drugs-and-inflammatory-cytokines-on-the-development-of-drug-induced-liver-injury
#16
J Jiang, K Mathijs, L Timmermans, S M Claessen, A Hecka, J Weusten, R Peters, J H van Delft, J C S Kleinjans, D G J Jennen, T M de Kok
The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733205/-dehydrofukinone-modulates-membrane-potential-and-delays-seizure-onset-by-gabaa-receptor-mediated-mechanism-in-mice
#17
Quelen Iane Garlet, Luana da Costa Pires, Laura Hautrive Milanesi, Joseane Righes Marafiga, Bernardo Baldisserotto, Carlos Fernando Mello, Berta Maria Heinzmann
(+)-Dehydrofukinone (DHF), isolated from Nectandra grandiflora (Lauraceae) essential oil, induces sedation and anesthesia by modulation of GABAa receptors. However, no study has addressed whether DHF modulates other cellular events involved in the control of cellular excitability, such as seizure behavior. Therefore, the aim of the present study was to investigate the effect of DHF on cellular excitability and seizure behavior in mice. For this purpose, we used isolated nerve terminals (synaptosomes) to examine the effect of DHF on the plasma membrane potential, the involvement of GABAa receptors and the downstream activation of Ca(2+) mobilization...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28733204/the-polymorphism-xrcc1-arg194trp-and-8-hydroxydeoxyguanosine-increased-susceptibility-to-arsenic-related-renal-cell-carcinoma
#18
Yu-Mei Hsueh, Ying-Chin Lin, Wei-Jen Chen, Chao-Yuan Huang, Horng-Sheng Shiue, Yeong-Shiau Pu, Chi-Hung Chen, Chien-Tien Su
This study was designed to explore the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and renal cell carcinoma (RCC) and to investigate whether individuals with an XRCC1 risk genotype, a high level of 8-OHdG or a high urinary total arsenic concentration have a modified odds ratio (OR) of RCC. We recruited 180 RCC patients and 360 age- and sex-matched controls from a hospital-based pool. Image-guided biopsy or surgical resection of renal tumors was performed on RCC patients for pathological verification...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28625800/arsenic-alters-transcriptional-responses-to-pseudomonas-aeruginosa-infection-and-decreases-antimicrobial-defense-of-human-airway-epithelial-cells
#19
Britton C Goodale, Erica J Rayack, Bruce A Stanton
Arsenic contamination of drinking water and food threatens the health of hundreds of millions of people worldwide by increasing the risk of numerous diseases. Arsenic exposure has been associated with infectious lung disease in epidemiological studies, but it is not yet understood how ingestion of low levels of arsenic increases susceptibility to bacterial infection. Accordingly, the goal of this study was to examine the effect of arsenic on gene expression in primary human bronchial epithelial (HBE) cells and to determine if arsenic altered epithelial cell responses to Pseudomonas aeruginosa, an opportunistic pathogen...
June 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28624442/loss-of-fructose-1-6-bisphosphatase-induces-glycolysis-and-promotes-apoptosis-resistance-of-cancer-stem-like-cells-an-important-role-in-hexavalent-chromium-induced-carcinogenesis
#20
Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang
Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance...
June 15, 2017: Toxicology and Applied Pharmacology
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