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https://www.readbyqxmd.com/read/28535465/altered-glycometabolism-in-zebrafish-exposed-to-thifluzamide
#1
Yang Yang, Wenxian Liu, Dongzhi Li, Le Qian, Bin Fu, Chengju Wang
Thifluzamide exerts toxic effects to zebrafish and causes liver mitochondrial damage. To better understand the further mechanism, adult zebrafish were exposed to a range of thifluzamide concentrations (0, 0.019, 0.19, and 1.90 mg/L) for 28 days. In response to 1.90 mg/L exposure, liver glycogen significantly increased and blood glucose decreased. The expression of genes related to glycometabolism showed corresponding changes. Genes related to mtDNA replication and transcription and genes participating in mitochondrial complexes showed altered expression, which might lead to the inhibition of the tricarboxylic acid cycle (TCA)...
May 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28534856/manipulation-of-viral-micrornas-as-a-potential-antiviral-strategy-for-the-treatment-of-cytomegalovirus-infection
#2
Jiang Deng, Jun Xiao, Ping Ma, Bo Gao, Feng Gong, Liping Lv, Yanyu Zhang, Jinbo Xu
Cytomegalovirus (CMV) infection leads to notable morbidity and mortality in immunosuppressed patients. Current antiviral drugs are effective but seriously limited in their long-term use due to their relatively high toxicity. In the present study, we characterized the expression of murine CMV microRNAs (MCMV miRNAs) both in vitro and in vivo. Although 29 miRNAs were detectable during in vitro infection, only 11 miRNAs (classified as Group 1) were detectable during in vivo infection, and as many as 18 viral miRNAs (classified as Group 2) were less detectable (<50% of animals) in both the liver and lungs...
May 19, 2017: Viruses
https://www.readbyqxmd.com/read/28534445/differential-expression-of-micro-rnas-and-their-predicted-targets-in-renal-cells-exposed-to-amphotericin-b-and-its-complex-with-copper-ii-ions
#3
Joanna Magdalena Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Jolanta Adamska, Mariusz Gagoś, Urszula Mazurek
MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu(2+)) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu(2+)- induced changes in the miRNA profile of renal cells and to examine which biological processes are significantly affected by AmB-Cu(2+)...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28534439/hypolipidemic-and-hepatoprotective-activities-of-rosemary-and-thyme-in-gentamicin-treated-rats
#4
A M Hegazy, A S Abdel-Azeem, H M Zeidan, K S Ibrahim, Em El Sayed
Rosemary ( Rosmarinus officinalis; RM) and thyme ( Thymus vulgaris; TV) are used as remedies. We designed this work to investigate the preventive effect of aqueous extracts of RM or TV on the gentamicin (GM)-induced hepatotoxicity and abnormalities of lipid profile in rats. Both plant extracts exhibited an in vitro antioxidant activity as determined by the 1,1-diphenyl-2-picrylhydrazyl assay. Radical scavenging activity for TV extract was 48.7% and for RM extract was 25.6%. Polyphenolic determination by high-performance liquid chromatography for both extracts revealed that catechin, coumarin, cinnamic acid and rutin were detected in both extracts...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28534099/effects-of-intermittent-and-continuous-magnetic-fields-on-trace-element-levels-in-guinea-pigs
#5
Onur Erdem, Cemal Akay, Sule Coşkun Cevher, Ayse Gulnihal Canseven, Ahmet Aydın, Nesrin Seyhan
Electromagnetic fields (EMFs) can affect living cells due to biochemical changes, followed by changes in levels of trace elements in serum and different organs. This study focuses on the effect of whole body exposure to EMF, presented everywhere in our environment, and on the levels of trace elements in serum, femur, brain, kidney, and liver tissues. The analyses performed on 29 guinea pigs were divided into five groups. Guinea pigs were exposed to a magnetic field of 50 Hz of 1.5 mT. Groups A and B were exposed to the magnetic field for a period of 4 h/day continuously (4 h/day) for 4 and 7 days, respectively...
May 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28533121/recent-progress-in-hepatocyte-culture-models-and-their-application-to-the-assessment-of-drug-metabolism-transport-and-toxicity-in-drug-discovery-the-value-of-tissue-engineering-for-the-successful-development-of-a-microphysiological-system
#6
REVIEW
Kazuhiro Tetsuka, Masato Ohbuchi, Kenji Tabata
Tissue engineering technology has provided many useful culture models. This article reviews the merits of this technology in a hepatocyte culture system, and describes the applications of the sandwich-cultured hepatocyte model in drug discovery. In addition, we also review recent investigations of the utility of the three-dimensional bioprinted human liver tissue model and spheroid model. Finally, we present the future direction and developmental challenges of a hepatocyte culture model for the successful establishment of a microphysiological system, represented as an organ-on-a-chip and even as a human-on-a-chip...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28532671/ochratoxin-a-transport-by-the-human-breast-cancer-resistance-protein-bcrp-multidrug-resistance-protein-2-mrp2-and-organic-anion-transporting-polypeptides-1a2-1b1-and-2b1
#7
Xiaozhe Qi, Els Wagenaar, Wentao Xu, Kunlun Huang, Alfred H Schinkel
Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pH7...
May 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28532263/establishment-and-assessment-of-a-novel-in-vitro-bio-pk-pd-system-in-predicting-the-in-vivo-pharmacokinetics-and-pharmacodynamics-of-cyclophosphamide
#8
Shanshan Tong, Hong Sun, Caifu Xue, Hanmei Chen, Jing Liu, Huiying Yang, Ning Zhou, Xiaoqiang Xiang, Weimin Cai
1. A novel bio-pharmacokinetic/pharmacodynamic (PK/PD) system was established and assessed in predicting the PK parameters and PD effects of the model drug cyclophosphamide (CP) considering the interrelationships between drug metabolism, pharmacological effects and dynamic blood circulation processes in vitro. 2. The system contains a peristaltic pump, a reaction chamber with rat liver microsomes (RLMs) encapsulated in pluronic F127-acrylamide-bisacrylamide (FAB) hydrogels, an effector cell chamber and a recirculating pipeline...
May 23, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28532222/bromuconazole-induced-hepatotoxicity-is-accompanied-by-upregulation-of-pxr-cyp3a1-and-downregulation-of-car-cyp2b1-gene-expression
#9
Doaa H Abdelhady, Mohammed A El-Magd, Zizy I Elbialy, Ayman A Saleh
Despite widespread use of bromuconazole as a pesticide for food crops and fruits, limited studies have been done to evaluate its toxic effects. Here, we evaluated the hepatotoxic effect of bromuconazole using classical toxicological (biochemical analysis and histopathological examination) and gene-based molecular methods. Male rats were treated either orally or topically with bromuconazole at doses equal to no observed adverse effect level (NOAEL) and 1/10 LD50 for 90 days. Bromuconazole increased activities of liver enzymes (ALT, AST, ALP, and ACP), and levels of bilirubin...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28532095/antitumor-activity-and-safety-evaluation-of-nanaparticle-based-delivery-of-quercetin-through-intravenous-administration-in-mice
#10
Jian Li, Ming Shi, Baoling Ma, Ruixu Niu, Haizhao Zhang, Li Kun
The present study focused on the inhibition effects and the safety evaluation of the quercetin when it was loaded into the nanoliposomes on cervical cancer in vitro and in vivo. Quercetin loaded nanoliposomes (Que-NLs) were first prepared by thin film hydration method and the characterizations of Que-NLs were measured with TEM and dynamic light scattering (DLS) techniques. Then the anti-cervical cancer efficiencies were evaluated by MTT and U14 tumor-bearing mice models in vitro and in vivo respectively. The body changes, organ index, biochemical criterions and histopathological of livers and kidneys in tumor-bearing mice were further assayed to evaluate the safety of Que-NLs...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531996/poly-epsilon-caprolactone-nanoparticles-enhance-ursolic-acid-in-vivo-efficacy-against-trypanosoma-cruzi-infection
#11
Juliana Palma Abriata, Josimar O Eloy, Thalita Bachelli Riul, Patricia Mazureki Campos, Marcelo Dias Baruffi, Juliana Maldonado Marchetti
Despite affecting millions of people worldwide, Chagas disease is still neglected by the academia and industry and the therapeutic option available, benznidazole, presents limited efficacy and side effects. Within this context, ursolic acid may serve as an option for treatment, however has low bioavailability, which can be enhanced through the encapsulation in polymeric nanoparticles. Therefore, herein we developed ursolic acid-loaded nanoparticles with poly-ε-caprolactone by the nanoprecipitation method and characterized them for particle size, zeta potential, polydispersity, encapsulation efficiency, morphology by scanning electron microscopy and thermal behavior by differential scanning calorimetry...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531990/safety-protocol-for-the-gold-nanoparticles-administration-in-rats
#12
Alexandre Pastoris Muller, Gabriela Kozuchovski Ferreira, Sabrina da Silva, Renata Tiscoski Nesi, Gustavo de Bem Silveira, Carolini Mendes, Ricardo A Pinho, Marcos Marques da Silva Paula, Paulo Cesar Lock Silveira
Gold nanoparticles (GNPs) have antioxidant and anti-inflammatory effects. However, toxicity is still a concern; therefore, it is critical to study both the therapeutic and toxic properties of GNPs. In this study, we evaluated the effects of the intraperitoneal administration of GNPs (20nm, at a concentration of 2.5mg/L for 21days) every 24 or 48h on oxidative stress, antioxidant status, and electron chain transport (ETC) in the brain. Liver histology and blood marker analyses were conducted to establish a time routine of GNP administration...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531838/antimicrobial-agents-triclosan-chloroxylenol-methylisothiazolinone-and-borax-used-in-cleaning-had-genotoxic-and-histopathologic-effects-on-rainbow-trout
#13
Erol Capkin, Tuna Ozcelep, Sevki Kayis, Ilhan Altinok
Triclosan (TRC), chloroxylenol (PCMX) and methylisothiazolinone (MIT) have been commonly used as an antimicrobial in soaps while borax (BRX) is used in household cleaning. After using these chemicals, they are washed down drains and getting into the aquatic ecosystem in which they may affect aquatic living organisms. In the present study, the chronic effects of TRC, PCMX, MIT and BRX on genotoxicity, gene expression and histopathology of rainbow trout (Oncorhynchus mykiss) were evaluated for 40 days under semi static condition...
May 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28531339/limtox-a-web-tool-for-applied-text-mining-of-adverse-event-and-toxicity-associations-of-compounds-drugs-and-genes
#14
Andres Cañada, Salvador Capella-Gutierrez, Obdulia Rabal, Julen Oyarzabal, Alfonso Valencia, Martin Krallinger
A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28530135/prolonged-expression-of-secreted-enzymes-in-dogs-after-liver-directed-delivery-of-i-sleeping-beauty-i-transposons-implications-for-non-viral-gene-therapy-of-systemic-disease
#15
Elena L Aronovich, Kendra Anne Hyland, Bryan C Hall, Jason B Bell, Erik R Olson, Myra Urness Rusten, David W Hunter, N Matthew Ellinwood, R Scott McIvor, Perry B Hackett
The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice including hemophilias A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis (MPS) types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively. We recently reported modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), we demonstrated transgenic protein in the plasma for up to six weeks post-infusion...
May 20, 2017: Human Gene Therapy
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
#16
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/28528917/pazopanib-gw786034-and-cyclophosphamide-in-patients-with-platinum-resistant-recurrent-pre-treated-ovarian-cancer-results-of-the-pacovar-trial
#17
C Dinkic, M Eichbaum, M Schmidt, E M Grischke, G Gebauer, H C Fricke, F Lenz, M Wallwiener, F Marme, A Schneeweiss, C Sohn, J Rom
PURPOSE: The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. PATIENTS AND METHODS: This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously treated ovarian, peritoneal, or fallopian tube cancer...
May 18, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28528816/vertical-transmission-of-microcystins-to-nile-crocodile-crocodylus-niloticus-eggs
#18
Alukhethi Singo, Jan G Myburgh, Peter N Laver, Elizabeth A Venter, Gezina C H Ferreira, Gertruida M Rösemann, Christo J Botha
Cyanobacteria or blue green algae are known for their extensive and highly visible blooms in eutrophic, stagnant freshwater bodies. Climate change and global warming have also contributed to a rise in toxic cyanobacterial blooms. One of the most important cyanobacteria is Microcystis aeruginosa, which can synthesize various microcystins that can affect the health of terrestrial and aquatic animals. Commercial Nile crocodile (Crocodylus niloticus) farming in South Africa is based on keeping breeders (adult males and females) in big dams on farms (captive-bred approach)...
May 18, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28528318/metabolic-profiling-of-goldfish-carassius-auratis-after-long-term-glyphosate-based-herbicide-exposure
#19
Ming-Hui Li, Ling-Yu Ruan, Jin-Wei Zhou, Yong-Hong Fu, Lei Jiang, He Zhao, Jun-Song Wang
Glyphosate is an efficient herbicide widely used worldwide. However, its toxicity to non-targeted organisms has not been fully elucidated. In this study, the toxicity of glyphosate-based herbicide was evaluated on goldfish (Carassius auratus) after long-term exposure. Tissues of brains, kidneys and livers were collected and submitted to NMR-based metabolomics analysis and histopathological inspection. Plasma was collected and the blood biochemical indexes of AST, ALT, BUN, CRE, LDH, SOD, GSH-Px, GR and MDA were measured...
May 13, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28527914/impact-of-hepatic-p450-mediated-biotransformation-on-the-disposition-and-respiratory-tract-toxicity-of-inhaled-naphthalene
#20
Nataliia Kovalchuk, Jacklyn Kelty, Lei Li, Matthew Hartog, Qing-Yu Zhang, Patricia Edwards, Laura Van Winkle, Xinxin Ding
We determined whether a decrease in hepatic microsomal cytochrome P450 activity would impact lung toxicity induced by inhalation exposure to naphthalene (NA), a ubiquitous environmental pollutant. The liver-Cpr-null (LCN) mouse showed decreases in microsomal metabolism of NA in liver, but not lung, compared to wild-type (WT) mouse. Plasma levels of NA and NA-glutathione conjugates (NA-GSH) were both higher in LCN than in WT mice after a 4-h nose-only NA inhalation exposure at 10ppm. Levels of NA were also higher in lung and liver of LCN, compared to WT, mice, following exposure to NA at 5 or 10ppm...
May 17, 2017: Toxicology and Applied Pharmacology
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