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Toxicology and Applied Pharmacology

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https://www.readbyqxmd.com/read/29343424/igf1-mapk-erk-signaling-pathway-mediated-programming-alterations-of-adrenal-cortex-cell-proliferation-by-prenatal-caffeine-exposure-in-male-offspring-rats
#1
Guanghui Chen, Chao Yuan, Fangfang Duan, Yanyan Liu, Jinzhi Zhang, Zheng He, Hegui Huang, Chunjiang He, Hui Wang
Our previous study proposed a glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis programming mechanism for prenatal caffeine exposure (PCE)-induced adrenal developmental dysfunction. Here, we focused on PCE-induced cell proliferation changes of the adrenal cortex in male offspring rats before and after birth and clarified the intrauterine programming mechanism. On gestational day (GD) 20, the PCE group had an elevated serum corticosterone level reduced fetal bodyweight, maximum adrenal sectional area, and elevated adrenal corticosterone and aldosterone contents...
January 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29329804/a-rapid-and-sensitive-fluorometric-method-for-determination-of-aldehyde-oxidase-activity
#2
Nancy Apenova, Hui Peng, Markus Hecker, Markus Brinkmann
Previous research has characterized the important role of aldehyde oxidases (AOX) in biotransformation of N-heterocyclic therapeutic drugs and environmental contaminants in mammals. Research pertaining to AOX activity in non-mammalian vertebrates, however, is scarce, despite its biological role as a potentially important metabolic pathway for xenobiotics. One of the limiting factors of research on AOX is that available photometric methods are relatively insensitive, limited in throughput, and prone to cross-reactivity from other enzymes...
January 9, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29325823/photo-geno-toxicity-changes-associated-with-hydroxylation-of-the-aromatic-chromophores-during-diclofenac-metabolism
#3
Guillermo Garcia-Lainez, Ana M Martínez-Reig, Daniel Limones-Herrero, M Consuelo Jiménez, Miguel A Miranda, Inmaculada Andreu
Diclofenac (DCF) can cause adverse reactions such as gastrointestinal, renal and cardiovascular disorders; therefore, topical administration may be an attractive alternative to the management of local pain in order to avoid these side effects. However, previous studies have shown that DCF, in combination with sunlight, displays capability to induce photosensitivity disorders. In humans, DCF is biotransformed into hydroxylated metabolites at positions 4' and 5 (4'OH-DCF and 5OH-DCF), and this chemical change produces non negligible alterations of the drug chromophore, resulting in a significant modification of its light-absorbing properties...
January 8, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29317240/toxicity-and-cardiac-effects-of-acute-exposure-to-tryptophan-metabolites-on-the-kynurenine-pathway-in-early-developing-zebrafish-danio-rerio-embryos
#4
Michal Majewski, Natalia Kasica, Anna Jakimiuk, Piotr Podlasz
Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of exposure to tryptophan metabolites might impact the early development of organism. Thus, this study examined the effects of KP exposure in zebrafish embryos starting at the blastula period (4hpf) and the segmentation stage (24hpf)...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29317239/protective-effect-of-mitochondrial-targeted-antioxidant-mitoq-against-iron-ion-56fe-radiation-induced-brain-injury-in-mice
#5
Lu Gan, Zhenhua Wang, Jing Si, Rong Zhou, Chao Sun, Yang Liu, Yancheng Ye, Yanshan Zhang, Zhiyuan Liu, Hong Zhang
Exposure to iron ion 56Fe radiation (IR) during space missions poses a significant risk to the central nervous system and radiation exposure is intimately linked to the production of reactive oxygen species (ROS). MitoQ is a mitochondria-targeted antioxidant that has been shown to decrease oxidative damage and lower mitochondrial ROS in a number of animal models. Therefore, the present study aimed to investigate role of the mitochondrial targeted antioxidant MitoQ against 56Fe particle irradiation-induced oxidative damage and mitochondria dysfunction in the mouse brains...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29309768/toxicity-and-related-mechanisms-of-dihydroartemisinin-on-porcine-oocyte-maturation-in-vitro
#6
Yan Luo, Man-Ju Che, Cong Liu, Hua-Ge Liu, Xiang-Wei Fu, Yun-Peng Hou
Dihydroartemisinin (DHA), the main active metabolite of artemisinin, has been used to treat malaria and has anticancer activities. Previous work has shown that DHA has negative impacts on embryos in rodents and primates. However, whether DHA has adverse effects on oocyte maturation is unknown. In the present study, we evaluated the toxic effects and possible mechanisms of DHA on porcine oocyte maturation. The results showed that exposure to DHA inhibited porcine oocyte polar body extrusion, and blocked cell cycle progression...
January 5, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29307816/neurotoxic-effect-of-oxaliplatin-comparison-with-its-oxalate-free-analogue-cis-ptii-1r-2r-dach-3-acetoxy-1-1-cyclobutanedicarboxylato-llc-1402-in-mice
#7
Anamaria Falcão Pereira, Francisco Fábio Bezerra de Oliveira, Bruno Wesley de Freitas Alves, Karoline Luanne Santos de Menezes, Aline Kelly Viana de Mesquita, Mario Roberto Pontes Lisboa, Kalina Kelma Oliveira de Sousa, Mariana Lima Vale
Studies suggest that oxalate is involved in the development oxaliplatin-induced peripheral sensory neuropathy (OPSN). This study aimed to compare the neurotoxic effects of oxaliplatin with its oxalate-free cytotoxic analogue cis-[PtII(1R,2R-DACH)(3-acetoxy-1,1-cyclobutanedicarboxylato)] (LLC-1402) in mice. Oxaliplatin and LLC-1402 were intravenously injected in male Swiss mice with a total of nine injections. Oxalate was intraperitoneally injected in other animals. The development of OPSN was evaluated using mechanical and thermal sensitivity tests...
January 4, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29294303/astragaloside-iv-protects-blood-brain-barrier-integrity-from-lps-induced-disruption-via-activating-nrf2-antioxidant-signaling-pathway-in-mice
#8
Hongli Li, Ping Wang, Fei Huang, Jinmei Jin, Hui Wu, Beibei Zhang, Zhifei Wang, Hailian Shi, Xiaojun Wu
Endothelial cells of cerebral microvessels are one of the components of blood-brain-barrier (BBB), which are connected by tight junctions (TJs). BBB disruption in cerebral diseases such as ischemic stroke, Alzhemer's disease, multiple sclerosis and traumatic brain injury is implicated to exacerbate the disease progression. Astragaloside IV (ASIV) isolated from Astragalus membranaceus prevents BBB breakdown in rodents induced with cerebral edema and experimental autoimmune encephalomyelitis. However, its underlying molecular mechanism has not been elucidated yet...
December 30, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29291430/the-potential-benefit-of-combined-versus-monotherapy-of-coenzyme-q10-and-fluoxetine-on-depressive-like-behaviors-and-intermediates-coupled-to-gsk-3%C3%AE-in-rats
#9
Sally A Abuelezz, Nevien Hendawy, Yosra Magdy
As a part of the serotoninergic dysfunction implicated in neurobiology of depression, evidence has focused on serotonin (5-HT) receptors downstream signaling intermediates including glycogen synthase kinase-3β (GSK-3β), cAMP response element binding protein (CREB) and brain derived neurotrophic factor (BDNF). Our team previously reported that coenzyme Q10 (CoQ10) exerted antidepressant-like effect in rats exposed to chronic unpredictable mid stress (CUMS) via elevating serotonin levels. However, the effect of CoQ10 has not been elucidated in downstream signaling molecules mediating 5HT receptors' effect involved in depressive disorder hitherto...
December 29, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29289672/a-multi-omics-analysis-reveals-metabolic-reprogramming-in-thp-1-cells-upon-treatment-with-the-contact-allergen-dncb
#10
Franz Mussotter, Sarah Potratz, Jan Budczies, Andreas Luch, Andrea Haase
Dendritic cell (DC) activation by contact allergens is one of the key steps in the development of allergic contact dermatitis (ACD). Recent evidence suggests that metabolic reprogramming is a prerequisite for the activation of DCs, macrophages and monocytes. Therefore, we used an integrated approach by combining proteomics and metabolomics to investigate the metabolism of human THP-1 cells in response to the strong contact allergen, 2,4-dinitrochlorobenzene (DNCB). Cells were treated with 5, 10 and 20μM DNCB for 4, 8, and 24h, respectively...
December 28, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29289671/melatonin-protects-mouse-spermatogonial-stem-cells-against-hexavalent-chromium-induced-apoptosis-and-epigenetic-histone-modification
#11
Yinghua Lv, Pengfei Zhang, Jiayin Guo, Zhendong Zhu, Xueliang Li, Dazhong Xu, Wenxian Zeng
Given the potential biological functions of spermatogonial stem cells (SSCs) in spermatogenesis and in delivering parental genetic information to the next generation, how these cells respond to environmental toxins and carcinogens should be investigated. We examined the toxic effect of hexavalent chromium (Cr(VI)) on global histone modifications and apoptotic signaling pathways in SSCs. We determined the effect of melatonin, one of the most powerful endogenous free radical scavengers and wide-spectrum antioxidants, in protecting SSCs from Cr(VI)-induced apoptosis and global histone modification by Western blot analysis...
December 28, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29288688/neuroprotective-activity-of-macamides-on-manganese-induced-mitochondrial-disruption-in-u-87-mg-glioblastoma-cells
#12
Kuljeet S Gugnani, Nguyen Vu, Alejandro N Rondón-Ortiz, Mark Böhlke, Timothy J Maher, Alejandro J Pino-Figueroa
Macamides are a distinct class of secondary metabolites, benzylamides of long chain fatty acids, which were isolated from the Peruvian plant Lepidium meyenii (Maca). As structural analogues of the endocannabinoid anandamide (AEA), they have demonstrated neuroprotective effects in vitro and in vivo. The purpose of this study was to demonstrate the neuroprotective activity of the macamides: N-(3-methoxybenzyl)oleamide (MAC 18:1), N-(3-methoxybenzyl)linoleamide (MAC 18:2) and N-(3-methoxybenzyl)linolenamide (MAC 18:3) in a neurotoxic environment caused by exposure of U-87 MG glioblastoma cells to manganese chloride (MnCl2)...
December 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29288687/distinctive-effects-of-licarin-a-on-lipolysis-mediated-by-pka-and-on-formation-of-brown-adipocytes-from-c3h10t1-2-mesenchymal-stem-cells
#13
Dahyeon Yoon, Khan Mohammad Imran, Yong-Sik Kim
Obesity increases with the positive energy imbalance and correlates with increased risks for metabolic diseases. Promotion of white adipose tissue beiging has received considerable attention due to possible usefulness for preventing obesity and the comorbidities. Licarin A (LA) is a compound derived from Mexican medicinal plant Aristolochia taliscana. Here, we report that LA stimulates the development of brown-like and beige-like adipocytes from C3H10T1/2 mesenchymal stem cells with phenotypic shifts to formation of smaller lipid droplets...
December 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29278688/stage-specific-metabolic-features-of-differentiating-neurons-implications-for-toxicant-sensitivity
#14
Johannes Delp, Simon Gutbier, Martin Cerff, Christin Zasada, Sebastian Niedenführ, Liang Zhao, Lena Smirnova, Thomas Hartung, Hanna Borlinghaus, Falk Schreiber, Jörg Bergemann, Jochem Gätgens, Martin Beyss, Salah Azzouzi, Tanja Waldmann, Stefan Kempa, Katharina Nöh, Marcel Leist
Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs...
December 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29274910/disruption-of-liver-development-and-coagulation-pathway-by-ochratoxin-a-in-embryonic-zebrafish
#15
Ting-Shuan Wu, Yu-Ting Lin, Ying-Tzu Huang, Ya-Chih Cheng, Feng-Yih Yu, Biing-Hui Liu
Ochratoxin A (OTA) is a mycotoxin that is found in various food and feed products. The molecular mechanisms that are associated with OTA hepatotoxicity and teratogenicity have not been extensively elucidated in a developing organism. In this study, the transcriptomic profile of zebrafish embryos indicates that hemostasis and blood coagulation are the top two pathways affected by OTA. The treatment of embryos with OTA was able to decrease the expression of genes that encode coagulation factors and liver markers, including f7, f9b, cp and vtna...
December 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29274354/ochratoxin-a-exposure-decreased-sperm-motility-via-the-ampk-and-pten-signaling-pathways
#16
Tian-Yu Zhang, Rui-Ying Wu, Yong Zhao, Chun-Shuang Xu, Wei-Dong Zhang, Wei Ge, Jing Liu, Zhong-Yi Sun, Shu-Hua Zou, Wei Shen
Ochratoxin A (OTA), a common mycotoxin found in nature, has been implicated as effecting the function of male reproductive systems. OTA exposure has been shown to decrease sperm production and quality, however, the underlying mechanisms remain unknown. In the current investigation boar sperm exposed to 10 and 100μM OTA in vitro for 24h resulted in significantly decreased motility, in the 100μM OTA treatment group when compared with the control group. The level of reactive oxygen species (ROS) was significantly increased in both of the OTA treatment groups...
December 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29253500/carnosic-acid-prevents-col1a2-transcription-through-the-reduction-of-smad3-acetylation-via-the-ampk%C3%AE-1-sirt1-pathway
#17
Yan Zhao, Xue Shi, Chunchun Ding, Dongcheng Feng, Yang Li, Yan Hu, Li Wang, Dongyan Gao, Xiaofeng Tian, Jihong Yao
Carnosic acid (CA), a major bioactive component in rosemary extract, has many biological and pharmaceutical activities. Smad3 acetylation can regulate the transcription of type I α2 collagen (COL1A2), which is the major component of the extracellular matrix (ECM). The aim of the current study was to evaluate whether CA inhibits COL1A2 transcription via the reduction of Smad3 acetylation against liver fibrosis. The results showed that CA treatment significantly suppressed COL1A2 transcription and markedly decreased the deposition of ECM induced by dimethylamine (DMN) in rats...
December 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29248466/leptin-suppresses-microrna-122-promoter-activity-by-phosphorylation-of-foxo1-in-hepatic-stellate-cell-contributing-to-leptin-promotion-of-mouse-liver-fibrosis
#18
Qing Cao, Xiaofei Zhu, Xuguang Zhai, Li Ji, Fangyun Cheng, Yiqi Zhu, Pengfei Yu, Yajun Zhou
Adipocytokine leptin promotes hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and was demonstrated to inhibit liver fibrosis and reduced HSC proliferation. Our previous study revealed that leptin reduced miR-122 level in HSCs. This study was aimed to investigate whether leptin affected miR-122 promoter and the underlying mechanisms in HSCs. Results showed that leptin inhibited miR-122 promoter activity...
December 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29248465/disposition-of-%C3%AE-n-methylamino-l-alanine-l-bmaa-a-neurotoxin-in-rodents-following-a-single-or-repeated-oral-exposure
#19
Suramya Waidyanatha, Kristen Ryan, J Michael Sanders, Jacob D McDonald, Christopher J Wegerski, Melanie Doyle-Eisle, C Edwin Garner
β-N-methylamino-l-alanine (L-BMAA) is produced by cyanobacteria (blue-green algae). Human exposure to L-BMAA occurs via consumption of L-BMAA-contaminated water and food. It is speculated that exposure to L-BMAA, and subsequent brain accumulation, may contribute to an increased incidence of neurodegenerative diseases indicating the need to evaluate risk of L-BMAA exposure to humans. As an initial step in this process, we have evaluated disposition following a single or repeated gavage administration of 1, 10 or 100mg/kg [14C]L-BMAA in rats and mice...
December 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29248464/decanoic-acid-suppresses-proliferation-and-invasiveness-of-human-trophoblast-cells-by-disrupting-mitochondrial-function
#20
Changwon Yang, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Decanoic acid (DA) is a medium-chain fatty acid used in the manufacture of various products including plastics, cosmetics, and lubricants. In addition to antiviral and antibacterial effects, DA's, reported biological activities include regulation of signaling pathways and redox homeostasis in various human cell types. The influence of DA on functional properties of human trophoblasts, including proliferation, invasion and apoptosis is currently unknown. In the present study, we evaluated the anti-proliferative and anti-invasive effects of DA on the human trophoblast cell line HTR8/SVneo...
December 14, 2017: Toxicology and Applied Pharmacology
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