scholarly journals Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing—A Review

2021 ◽  
Vol 22 (18) ◽  
pp. 9932
Author(s):  
Pornsiri Pitchakarn ◽  
Woorawee Inthachat ◽  
Jirarat Karinchai ◽  
Piya Temviriyanukul
Keyword(s):  
High Throughput Screening ◽  
Environmental Pollutants ◽  
Spot Test ◽  
Herbal Extract ◽  
Human Model ◽  
Future Perspective ◽  
In Vivo Model ◽  
Potential Health ◽  
Advantages And Disadvantages

Genomic instability, one of cancer’s hallmarks, is induced by genotoxins from endogenous and exogenous sources, including reactive oxygen species (ROS), diet, and environmental pollutants. A sensitive in vivo genotoxicity test is required for the identification of human hazards to reduce the potential health risk. The somatic mutation and recombination test (SMART) or wing spot test is a genotoxicity assay involving Drosophila melanogaster (fruit fly) as a classical, alternative human model. This review describes the principle of the SMART assay in conjunction with its advantages and disadvantages and discusses applications of the assay covering all segments of health-related industries, including food, dietary supplements, drug industries, pesticides, and herbicides, as well as nanoparticles. Chemopreventive strategies are outlined as a global health trend for the anti-genotoxicity of interesting herbal extract compounds determined by SMART assay. The successful application of Drosophila for high-throughput screening of mutagens is also discussed as a future perspective.

scholarly journals Phenotypic assays in yeast and zebrafish reveal drugs that rescue ATP13A2 deficiency

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ursula Heins-Marroquin ◽  
Paul P Jung ◽  
Maria Lorena Cordero-Maldonado ◽  
Alexander D Crawford ◽  
Carole L Linster
Keyword(s):  
Heavy Metal ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Testing ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Drug Repurposing ◽  
In Vivo Model ◽  
Inherited Disorders ◽  
Zebrafish Model

Abstract Mutations in ATP13A2 (PARK9) are causally linked to the rare neurodegenerative disorders Kufor-Rakeb syndrome, hereditary spastic paraplegia and neuronal ceroid lipofuscinosis. This suggests that ATP13A2, a lysosomal cation-transporting ATPase, plays a crucial role in neuronal cells. The heterogeneity of the clinical spectrum of ATP13A2-associated disorders is not yet well understood and currently, these diseases remain without effective treatment. Interestingly, ATP13A2 is widely conserved among eukaryotes, and the yeast model for ATP13A2 deficiency was the first to indicate a role in heavy metal homeostasis, which was later confirmed in human cells. In this study, we show that the deletion of YPK9 (the yeast orthologue of ATP13A2) in Saccharomyces cerevisiae leads to growth impairment in the presence of Zn2+, Mn2+, Co2+ and Ni2+, with the strongest phenotype being observed in the presence of zinc. Using the ypk9Δ mutant, we developed a high-throughput growth rescue screen based on the Zn2+ sensitivity phenotype. Screening of two libraries of Food and Drug Administration-approved drugs identified 11 compounds that rescued growth. Subsequently, we generated a zebrafish model for ATP13A2 deficiency and found that both partial and complete loss of atp13a2 function led to increased sensitivity to Mn2+. Based on this phenotype, we confirmed two of the drugs found in the yeast screen to also exert a rescue effect in zebrafish—N-acetylcysteine, a potent antioxidant, and furaltadone, a nitrofuran antibiotic. This study further supports that combining the high-throughput screening capacity of yeast with rapid in vivo drug testing in zebrafish can represent an efficient drug repurposing strategy in the context of rare inherited disorders involving conserved genes. This work also deepens the understanding of the role of ATP13A2 in heavy metal detoxification and provides a new in vivo model for investigating ATP13A2 deficiency.

Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience

Cephalalgia ◽  
2013 ◽  
Vol 33 (8) ◽  
pp. 540-553 ◽  
Author(s):  
Messoud Ashina ◽  
Jakob Møller Hansen ◽  
Jes Olesen
Keyword(s):  
Animal Models ◽  
Signaling Molecules ◽  
Human Model ◽  
In Vivo Model ◽  
Acute Migraine ◽  
Susceptibility Factors ◽  
Complex Events ◽  
In Vivo Animal Models

In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of new possible anti-migraine agents. In vivo animal models enable the study of vascular responses, neurogenic inflammation, peptide release and genetic predisposition and thus have provided leads in the search for migraine mechanisms. All animal-based results must, however, be validated in human studies because so far no animal models can predict the efficacy of new therapies for migraine. Given the nature of migraine attacks, fully reversible and treatable, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model. If such an endogenous substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed. Human models of migraine offer unique possibilities to study mechanisms responsible for migraine and to explore the mechanisms of action of existing and future anti-migraine drugs. The human model has played an important role in translational migraine research leading to the identification of three new principally different targets in the treatment of acute migraine attacks and has been used to examine other endogenous signaling molecules as well as genetic susceptibility factors. New additions to the model, such as advanced neuroimaging, may lead to a better understanding of the complex events that constitute a migraine attack, and better and more targeted ways of intervention.

scholarly journals Assessment and Optimizations of Candida albicansIn Vitro Biofilm Assays

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Matthew B. Lohse ◽  
Megha Gulati ◽  
Ashley Valle Arevalo ◽  
Adam Fishburn ◽  
Alexander D. Johnson ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Gene Deletion ◽  
Antifungal Drugs ◽  
Antifungal Compounds ◽  
Content Type ◽  
Advantages And Disadvantages ◽  
Different Types ◽  
Implanted Medical Devices

ABSTRACT Candida albicans biofilms have a significant medical impact due to their rapid growth on implanted medical devices, their resistance to antifungal drugs, and their ability to seed disseminated infections. Biofilm assays performed in vitro allow for rapid, high-throughput screening of gene deletion libraries or antifungal compounds and typically serve as precursors to in vivo studies. Here, we compile and discuss the protocols for several recently published C. albicans in vitro biofilm assays. We also describe improved versions of these protocols as well as novel in vitro assays. Finally, we consider some of the advantages and disadvantages of these different types of assays.

Establishment of an in vivo model for KCNJ5 dependent hyperaldosteronism

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
U Lichtenauer ◽  
PL Schmid ◽  
A Oßwald ◽  
I Renner-Müller ◽  
M Reincke ◽  
...  
Keyword(s):  
In Vivo Model

An in vivo Model for the Assessment of Acute Fibrinolytic Capacity of the Endothelium

1997 ◽  
Vol 78 (04) ◽  
pp. 1242-1248 ◽  
Author(s):  
David E Newby ◽  
Robert A Wright ◽  
Christopher A Ludlam ◽  
Keith A A Fox ◽  
Nicholas A Boon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Plasma Concentrations ◽  
In Vivo Model ◽  
Forearm Circulation ◽  
Von Willebrand ◽  
Local Release ◽  
Willebrand Factor

SummaryThe effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 μg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.

Closure of Fetoscopic Access Sites with Amniotic Extracellular Matrix Scaffolds in an In Vivo Model

2006 ◽  
Vol 66 (S 01) ◽  
Author(s):  
N Ochsenbein-Kölble ◽  
J Jani ◽  
G Verbist ◽  
L Lewi ◽  
K Marquardt ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
In Vivo Model ◽  
Extracellular Matrix Scaffolds

PERFUSION OF OVARIES IN VITRO AND IN VIVO

1972 ◽  
Vol 68 (2_Supplb) ◽  
pp. S285-S309 ◽  
Author(s):  
Kurt Ahrén ◽  
Per Olof Janson ◽  
Gunnar Selstam
Keyword(s):  
Perfusion System ◽  
Perfusion Technique ◽  
Preliminary Results ◽  
Advantages And Disadvantages

ABSTRACT This paper discusses in vivo and in vitro ovarian perfusion systems described so far in the literature. The interest is not focussed primarily on the results of these studies but rather on the advantages and disadvantages of the techniques and methods used. Another part of the paper summarizes the points which are most important, in our opinion, to take into consideration when developing an in vitro perfusion technique of the ovary. The last part of the paper gives a description of and some preliminary results from an in vitro perfusion system of the rabbit ovary which is under development in this laboratory.

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