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Zebrafish drug screen

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https://www.readbyqxmd.com/read/28520533/a-fully-automated-high-throughput-zebrafish-behavioral-ototoxicity-assay
#1
Douglas W Todd, Rohit C Philip, Maki Niihori, Ryan A Ringle, Kelsey R Coyle, Sobia F Zehri, Jordan A Mudery, Ross H Francis, Jeffrey J Rodriguez, Abraham Jacob
Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells...
May 18, 2017: Zebrafish
https://www.readbyqxmd.com/read/28516375/effects-of-bothrops-alternatus-venom-in-zebrafish-a-histopathological-study
#2
José Carlos Tavares Carvalho, Hady Keita, Giovanna Rocha Santana, Gisele Custódio de Souza, Igor Victor Ferreira Dos Santos, Jesus Rafael Rodriguez Amado, Ansoumane Kourouma, Ariadna Lafourcade Prada, Helison de Oliveira Carvalho, Maria Lúcia Silva
Zebrafish is an excellent model organism for studying tissue alterations caused by Bothrops alternatus venom (BAV) and for screening new anti-venom drugs. To study tissue alterations following exposure to BAV and the roles that glucocorticoids play in these tissue reactions, zebrafish were randomly divided into five groups: the free injection control group (FIC), the phosphate-buffered saline injection control group (PIC), the venom injected group (VI), the group treated with dexamethasone 1 h before venom injection (D1hBVI) and the group treated with dexamethasone 1 h after venom injection (D1hAVI)...
May 17, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28515725/application-of-zebrafish-models-in-inflammatory-bowel-disease
#3
REVIEW
Li Hanyang, Liu Xuanzhe, Chen Xuyang, Qiu Yujia, Fu Jiarong, Shen Jun, Ran Zhihua
Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting inflammatory disease with unclear etiology. As a clinically frequent disease, it can affect individuals throughout their lives, with multiple complications. Unfortunately, traditional murine models are not efficient for the further study of IBD. Thus, effective and convenient animal models are needed. Zebrafish have been used as model organisms to investigate IBD because of their suggested highly genetic similarity to humans and their superiority as laboratory models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28515222/zebrafish-models-for-functional-and-toxicological-screening-of-nanoscale-drug-delivery-systems-promoting-preclinical-applications
#4
Keon Yong Lee, Gun Hyuk Jang, Cho Hyun Byun, Minhong Jeun, Peter Searson, Kwan Hyi Lee
Preclinical screening with animal models is an important initial step in clinical translation of new drug delivery systems. However, establishing efficacy, biodistribution, and biotoxicity of complex, multicomponent systems in small animal models can be expensive and time consuming. Zebrafish models represent an alternative for preclinical studies of nanoscale drug delivery systems. These models allow easy optical imaging, large sample size, and organ-specific studies, and hence an increasing number of preclinical studies are employing zebrafish models...
May 17, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28488933/zebrafish-as-a-screening-model-for-testing-the-permeability-of-blood-brain-barrier-to-small-molecules
#5
Seong Soon Kim, So Hee Im, Jung Yoon Yang, Yu-Ri Lee, Geum Ran Kim, Jin Sil Chae, Dae-Seop Shin, Jin Sook Song, Sunjoo Ahn, Byung Hoi Lee, Jae Chun Woo, Jin Hee Ahn, Chang Soo Yun, Phiho Kim, Hyoung Rae Kim, Kyeong-Ryoon Lee, Myung Ae Bae
The objective of this study was to evaluate the permeability of small molecules into the brain via the blood-brain barrier in zebrafish and to investigate the possibility of using this animal model as a screening tool during the early stages of drug discovery. Fifteen compounds were used to understand the permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma concentration was compared between the two animal models. The partition coefficient (Kp,brain), estimated using the concentration ratio at designated times (0...
May 10, 2017: Zebrafish
https://www.readbyqxmd.com/read/28475764/the-chaperone-activity-of-4pba-ameliorates-the-skeletal-phenotype-of-chihuahua-a-zebrafish-model-for-dominant-osteogenesis-imperfecta
#6
Roberta Gioia, Francesca Tonelli, Ilaria Ceppi, Marco Biggiogera, Sergey Leikin, Shannon Fisher, Elena Tenedini, Timur A Yorgan, Thorsten Schinke, Kun Tian, Jean-Marc Schwartz, Fabiana Forte, Raimund Wagener, Simona Villani, Antonio Rossi, Antonella Forlino
Classical osteogenesis imperfecta (OI) is a bone disease caused by type I collagen mutations and characterized by bone fragility, frequent fractures in absence of trauma and growth deficiency. No definitive cure is available for OI and to develop novel drug therapies, taking advantage of a repositioning strategy, the small teleost zebrafish (Danio rerio) is a particularly appealing model. Its small size, high proliferative rate, embryo transparency and small amount of drug required make zebrafish the model of choice for drug screening studies, when a valid disease model is available...
May 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28475330/discovery-and-characterization-of-r-s-n-3-cyanophenyl-n-6-tert-butoxycarbonylamino-3-4-dihydro-2-2-dimethyl-2h-1-benzopyran-4-yl-urea-a-new-histone-deacetylase-class-iii-inhibitor-exerting-antiproliferative-activity-against-cancer-cell-lines
#7
Michael Schnekenburger, Eric Goffin, Jin-Young Lee, Jun Young Jang, Aloran Mazumder, Seungwon Ji, Bernard Rogister, Nafila Bouider, Florence Lefranc, Walter Miklos, Véronique Mathieu, Pascal De Tullio, Kyu-Won Kim, Mario Dicato, Walter Berger, Byung Woo Han, Robert Kiss, Bernard Pirotte, Marc Diederich
A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. Based on computational docking combined to in vitro sirtuin 1/2 inhibition assays, we selected compound 18 [R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea] which displays a potent antiproliferative activity on various glioma cell types, assessed by quantitative videomicroscopy, eventually triggering senescence...
May 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28475237/production-of-zebrafish-cardiospheres-and-cardiac-progenitor-cells-in-vitro-and-three-dimensional-culture-of-adult-zebrafish-cardiac-tissue-in-scaffolds
#8
Wendy R Zeng, Siew-Joo Beh, Robert J Bryson-Richardson, Pauline M Doran
The hearts of adult zebrafish (Danio rerio) are capable of complete regeneration in vivo even after major injury, making this species of particular interest for understanding the growth and differentiation processes required for cardiac tissue engineering. To date, little research has been carried out on in vitro culture of adult zebrafish cardiac cells. In this work, progenitor-rich cardiospheres suitable for cardiomyocyte differentiation and myocardial regeneration were produced from adult zebrafish hearts...
May 5, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28468832/little-fish-big-data-zebrafish-as-a-model-for-cardiovascular-and-metabolic-disease
#9
REVIEW
Philipp Gut, Sven Reischauer, Didier Y R Stainier, Rima Arnaout
The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28459655/comparative-analyses-of-zebrafish-anxiety-like-behavior-using-conflict-based-novelty-tests
#10
Elana V Kysil, Darya A Meshalkina, Erin E Frick, David J Echevarria, Denis B Rosemberg, Caio Maximino, Monica Gomes Lima, Murilo S Abreu, Ana C Giacomini, Leonardo J G Barcellos, Cai Song, Allan V Kalueff
Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing...
May 1, 2017: Zebrafish
https://www.readbyqxmd.com/read/28449103/novel-degenerative-and-developmental-defects-in-a-zebrafish-model-of-mucolipidosis-type-iv
#11
Huiqing Li, Wuhong Pei, Sivia Vergarajauregui, Patricia M Zerfas, Nina Raben, Shawn M Burgess, Rosa Puertollano
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study we used genome editing to knockout the two mcoln1 genes present in Dario rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28438663/acute-effects-of-amitriptyline-on-adult-zebrafish-potential-relevance-to-antidepressant-drug-screening-and-modeling-human-toxidromes
#12
Konstantin A Demin, Tatiana O Kolesnikova, Sergey L Khatsko, Darya M Meshalkina, Evgeniya V Efimova, Yuri Yu Morzherin, Allan V Kalueff
The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline...
April 21, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28431223/pink1-based-screen-shines-light-on-autophagy-enhancers-for-parkinson-s-disease
#13
Dominik Haddad, Ken Nakamura
In this issue of Cell Chemical Biology, Zhang et al. (2017) report a zebrafish model of Parkinson's disease (PD), incorporating the PD-protein PINK1 and rotenone, a toxin linked to PD. Using it as a drug-screening platform, they identify trifluoperazine and other piperazine phenothiazines as protective compounds that enhance autophagy independent of PINK1.
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28424313/reduction-in-activity-by-noxious-chemical-stimulation-is-ameliorated-by-immersion-in-analgesic-drugs-in-zebrafish
#14
Javier Lopez-Luna, Qussay Al-Jubouri, Waleed Al-Nuaimy, Lynne U Sneddon
Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days post-fertilization were exposed to known noxious stimuli: acetic acid (0...
April 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28423345/homocysteine-induced-peripheral-microcirculation-dysfunction-in-zebrafish-and-its-attenuation-by-l-arginine
#15
Sang Joon Lee, Sung Ho Park, Jinhyuk Fred Chung, Woorak Choi, Hyung Kyu Huh
Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter V¯CV/V¯PCV, where V¯CV and V¯PCV represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422076/zeglobaltox-an-innovative-approach-to-address-organ-drug-toxicity-using-zebrafish
#16
Carles Cornet, Simone Calzolari, Rafael Miñana-Prieto, Sylvia Dyballa, Els van Doornmalen, Helma Rutjes, Thierry Savy, Davide D'Amico, Javier Terriente
Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28409342/zebrafish-as-a-model-of-kidney-disease
#17
Elvin E Morales, Rebecca A Wingert
Animal models have been an invaluable means to advance biomedical research as they provide experimental avenues for cellular and molecular investigations of disease pathology. The zebrafish (Danio rerio) is a good alternative to mammalian models that can be used to apply powerful genetic experimental methods normally used in invertebrates to answer questions about vertebrate development and disease. In the case of the kidney, the zebrafish has proven itself to be an applicable and versatile experimental system, mainly due to the simplicity of its pronephros, which contains two nephrons that possess conserved structural and physiological aspects with mammalian nephrons...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28408289/dopaminergic-control-of-anxiety-in-young-and-aged-zebrafish
#18
Victoria Kacprzak, Neil A Patel, Elizabeth Riley, Lili Yu, Jing-Ruey J Yeh, Irina V Zhdanova
Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wild type (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed...
April 10, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28385158/a-multi-animal-tracker-for-studying-complex-behaviors
#19
Eyal Itskovits, Amir Levine, Ehud Cohen, Alon Zaslaver
BACKGROUND: Animals exhibit astonishingly complex behaviors. Studying the subtle features of these behaviors requires quantitative, high-throughput, and accurate systems that can cope with the often rich perplexing data. RESULTS: Here, we present a Multi-Animal Tracker (MAT) that provides a user-friendly, end-to-end solution for imaging, tracking, and analyzing complex behaviors of multiple animals simultaneously. At the core of the tracker is a machine learning algorithm that provides immense flexibility to image various animals (e...
April 6, 2017: BMC Biology
https://www.readbyqxmd.com/read/28378824/chemical-inhibition-reveals-differential-requirements-of-signaling-pathways-in-kras-v12-and-myc-induced-liver-tumors-in-transgenic-zebrafish
#20
Chuan Yan, Qiqi Yang, Xiaojing Huo, Hankun Li, Li Zhou, Zhiyuan Gong
Previously we have generated inducible liver tumor models by transgenic expression of an oncogene and robust tumorigenesis can be rapidly induced by activation of the oncogene in both juvenile and adult fish. In the present study, we aimed at chemical intervention of tumorigenesis for understanding molecular pathways of tumorigenesis and for potential development of a chemical screening tool for anti-cancer drug discovery. Thus, we evaluated the roles of several major signaling pathways in kras(V12)- or Myc-induced liver tumors by using several small molecule inhibitors: SU5402 and SU6668 for VEGF/FGF signaling; IWR1 and cardionogen 1 for Wnt signaling; and cyclopamine and Gant61 for Hedgehog signaling...
April 5, 2017: Scientific Reports
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