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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/28219650/dendritic-cells-death-induced-by-contact-sensitizers-is-controlled-by-nrf2-and-depends-on-glutathione-levels
#1
Zeina El Ali, Claudine Deloménie, Jérémie Botton, Marc Pallardy, Saadia Kerdine-Römer
Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action...
February 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28215996/morphological-and-behavioral-responses-of-zebrafish-after-24h-of-ketamine-embryonic-exposure
#2
Luís M Félix, Cindy Serafim, Maria J Martins, Ana M Valentim, Luís M Antunes, Manuela Matos, Ana M Coimbra
Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24h-LC50 was calculated from percent survival using probit analysis. Based on the 24h-LC50 (94.4mgL(-1)), embryos (2hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24h to ketamine concentrations of 50, 70 or 90mgL(-1)...
February 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213093/enhanced-effect-of-geldanamycin-nanocomposite-against-breast-cancer-cells-growing-in-vitro-and-as-xenograft-with-vanquished-normal-cell-toxicity
#3
Suma Prabhu, Preeta Ananthanarayanan, Kannangar Aziz Sajida, Sharada Rai, Srinivas Mutalik, Satish Rao Bola Sadashiva
Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#4
Willem van den Brink, Annette Emerenciana, Francesco Bellanti, Oscar Della Pasqua, Jan Willem van der Laan
Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213091/convergence-of-hepcidin-deficiency-systemic-iron-overloading-heme-accumulation-and-rev-erb%C3%AE-%C3%AE-activation-in-aryl-hydrocarbon-receptor-elicited-hepatotoxicity
#5
Kelly A Fader, Rance Nault, Mathew P Kirby, Gena Markous, Jason Matthews, Timothy R Zacharewski
Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01-30μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4days for 28days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213090/glycyrrhetinic-acid-attenuates-lipopolysaccharide-induced-fulminant-hepatic-failure-in-d-galactosamine-sensitized-mice-by-up-regulating-expression-of-interleukin-1-receptor-associated-kinase-m
#6
Xinru Yin, Xia Gong, Li Zhang, Rong Jiang, Ge Kuang, Bin Wang, Xinyu Chen, Jingyuan Wan
Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100mg/kg) 1h before lipopolysaccharide (LPS)/d-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28193520/mdr1a-plays-a-crucial-role-in-regulating-the-analgesic-effect-and-toxicity-of-aconitine-by-altering-its-pharmacokinetic-characteristics
#7
Lijun Zhu, Jinjun Wu, Min Zhao, Wenjie Song, Xiaoxiao Qi, Ying Wang, Linlin Lu, Zhongqiu Liu
Aconitine (AC) is the primary bioactive/toxic alkaloid in plants of the Aconitum species. Our previous study demonstrated that Mdr1 was involved in efflux of AC. However, the mechanism by which Mdr1 regulates the efficacy/toxicity of AC in vivo remains unclear. The present study aimed to determine the effects of Mdr1a on the efficacy/toxicity and pharmacokinetics of AC in wild-type and Mdr1a(-/-) FVB mice. After oral administration of AC, significantly higher analgesic effect was observed in Mdr1a(-/-) mice (49% to 105%) compared to wild-type mice (P<0...
February 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28193519/thiamine-deficiency-induces-endoplasmic-reticulum-stress-and-oxidative-stress-in-human-neurons-derived-from-induced-pluripotent-stem-cells
#8
Xin Wang, Mei Xu, Jacqueline A Frank, Zun-Ji Ke, Jia Luo
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear...
February 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28189652/relationship-between-mercury-in-kidney-blood-and-urine-in-environmentally-exposed-individuals-and-implications-for-biomonitoring
#9
Magnus Akerstrom, Lars Barregard, Thomas Lundh, Gerd Sallsten
BACKGROUND: Individuals without occupational exposure are exposed to mercury (Hg) from diet and dental amalgam. The kidney is a critical organ, but there is limited information regarding the relationship between Hg in kidney (K-Hg), urine (U-Hg), blood (B-Hg), and plasma (P-Hg). OBJECTIVES: The aim was to determine the relationship between K-Hg, U-Hg, B-Hg, and P-Hg among environmentally exposed individuals, estimate the biological half-time of K-Hg, and provide information useful for biomonitoring of Hg...
February 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28189653/corrigendum-to-activation-of-ampk-by-berberine-induces-hepatic-lipid-accumulation-by-upregulation-of-fatty-acid-translocase-cd36-in-mice-toxicol-appl-pharmacol-316-2017-74-82
#10
You-Jin Choi, Kang-Yo Lee, Seung-Hwan Jung, Hyung Sik Kim, Gayong Shim, Mi-Gyeong Kim, Yu-Kyoung Oh, Seon-Hee Oh, Dae Won Jun, Byung-Hoon Lee
No abstract text is available yet for this article.
February 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28185818/amentoflavone-protects-dopaminergic-neurons-in-mptp-induced-parkinson-s-disease-model-mice-through-pi3k-akt-and-erk-signaling-pathways
#11
Qin Cao, Liyue Qin, Fei Huang, Xiaoshuang Wang, Liu Yang, Hailian Shi, Hui Wu, Beibei Zhang, Ziyu Chen, Xiaojun Wu
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP(+))-induced nuclear condensation and loss of cell viability without obvious cytotoxicity...
February 6, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28174120/xenobiotics-and-the-glucocorticoid-receptor
#12
REVIEW
Linda S M Gulliver
Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28174119/potential-transfer-of-neurotoxic-amino-acid-%C3%AE-n-methylamino-alanine-bmaa-from-mother-to-infant-during-breast-feeding-predictions-from-human-cell-lines
#13
Marie Andersson, Lisa Ersson, Ingvar Brandt, Ulrika Bergström
β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [(14)C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [(14)C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28167223/anti-allergic-activity-of-2-4-6-trihydroxy-3-geranylacetophenone-thga-via-attenuation-of-ige-mediated-mast-cell-activation-and-inhibition-of-passive-systemic-anaphylaxis
#14
Ji Wei Tan, Daud Ahmad Israf, Hanis Hazeera Harith, Nur Fariesha Md Hashim, Chean Hui Ng, Khozirah Shaari, Chau Ling Tham
tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28167222/identification-of-sperm-mrna-biomarkers-associated-with-testis-injury-during-preclinical-testing-of-pharmaceutical-compounds
#15
Edward Dere, Daniel J Spade, Susan J Hall, Aimee Altemus, James D Smith, Jonathan A Phillips, Jeffrey S Moffit, Kerry T Blanchard, Kim Boekelheide
The human testis is sensitive to toxicant-induced injury but current methods for detecting adverse effects are limited, insensitive and unreliable. Animal studies use sensitive histopathological endpoints to assess toxicity, but require testicular tissue that is not available during human clinical trials. More sensitive and reliable molecular biomarkers of testicular injury are needed to better monitor testicular toxicity in both clinical and preclinical. Adult male Wistar Han rats were exposed for 4weeks to compounds previously associated with testicular injury, including cisplatin (0, 0...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28167221/toxicological-evaluation-of-5-methoxy-2-aminoindane-meai-binge-mitigating-agent-in-development
#16
Jakob A Shimshoni, Ilan Winkler, Nir Edery, Ezekiel Golan, René van Wettum, David Nutt
5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound of the aminoindane class, which in recent years has been recreationally used by many people, who reported of a mild euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. In the light of these observations it was decided to progress MEAI through a preliminary drug development route and evaluate the acute and subacute toxicity of MEAI administrated orally to Sprague Dawley rats, as well as to determine potential in-vitro cytotoxic and mutagenic effects using state-of-the-art protocols...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28162991/improving-the-international-agency-for-research-on-cancer-s-consideration-of-mechanistic-evidence
#17
Julie Goodman, Heather Lynch
BACKGROUND: The International Agency for Research on Cancer (IARC) recently developed a framework for evaluating mechanistic evidence that includes a list of 10 key characteristics of carcinogens. This framework is useful for identifying and organizing large bodies of literature on carcinogenic mechanisms, but it lacks sufficient guidance for conducting evaluations that fully integrate mechanistic evidence into hazard assessments. OBJECTIVES: We summarize the framework, and suggest approaches to strengthen the evaluation of mechanistic evidence using this framework...
February 3, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28132918/ciproxifan-a-histamine-h3-receptor-antagonist-and-inverse-agonist-presynaptically-inhibits-glutamate-release-in-rat-hippocampus
#18
Cheng-Wei Lu, Tzu-Yu Lin, Chia-Ying Chang, Shu-Kuei Huang, Su-Jane Wang
Ciproxifan is an H3 receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Cav2...
January 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28130038/autophagy-contributes-to-4-amino-2-trifluoromethyl-phenyl-retinate-induced-differentiation-in-human-acute-promyelocytic-leukemia-nb4-cells
#19
Yue Li, Ge Li, Ke Wang, Ya-Ya Xie, Ren-Peng Zhou, Yao Meng, Ran Ding, Jin-Fang Ge, Fei-Hu Chen
As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study...
January 25, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28109817/salecan-protected-against-concanavalin-a-induced-acute-liver-injury-by-modulating-t-cell-immune-responses-and-nmr-based-metabolic-profiles
#20
Qi Sun, Xi Xu, Xiao Yang, Dan Weng, Junsong Wang, Jianfa Zhang
Salecan, a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, has been reported to exhibit a wide range of biological effects. The aims of the present study were to investigate the protective effect of salecan against Concanavalin A (ConA)-induced hepatitis, a well-established animal model of immune-mediated liver injury, and to search for possible mechanisms. C57BL/6 mice were pretreated with salecan followed by ConA injection. Salecan treatment significantly reduced ConA-induced acute liver injury, and suppressed the expression and secretion of inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-6 and IL-1β in ConA-induced liver injury model...
January 19, 2017: Toxicology and Applied Pharmacology
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