Optimizing multi-dimensional high throughput screening using zebrafish

Truong, Lisa; Bugel, Sean M.; Chlebowski, Anna C.; Usenko, Crystal Y.; Simonich, Michael T.; Simonich, Staci L. Massey; Tanguay, Robert L.

doi:10.1016/j.reprotox.2016.05.015

Cited by 50 publications

(68 citation statements)

References 27 publications

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“…The 10 mM stock solutions were dispensed using the Hewlett-Packard D300 Digital Dispenser, an inkjet technology that can directly deliver the chemical at the desired concentration into the experimental chamber. A lower energy mixing protocol was scripted for the HP D300 and implemented to automatically mix for 1 sec between all deliveries of at least 5 nL (Truong et al, 2016), again for 15 sec after each dispense head on the cassette was exhausted (on average after every 16 wells, dependent on the protocol), then again for 15 sec after the HP D300 completed the plate (Truong et al, 2016). All wells were normalized with 0.64% DMSO.…”

Section: Methodsmentioning

confidence: 99%

Assessment of the developmental and neurotoxicity of the mosquito control larvicide, pyriproxyfen, using embryonic zebrafish

Truong

Gonnerman

Simonich

et al. 2016

Environmental Pollution

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In 2014, as an attempt to address the Zika health crisis by controlling the mosquito population, Brazil took the unprecedented action of applying a chemical larvicide, pyriproxyfen, to drinking water sources. The World Health Organization has established an acceptable daily intake of pyriproxyfen to be 100 micrograms per kg of body weight per day, but studies have demonstrated that at elevated doses (>5000 mg/kg), there are adverse effects in mice, rats and dogs. To better understand the potential developmental toxicity of pyriproxyfen, we utilized the embryonic zebrafish. Our results demonstrate that the concentration resulting in 50% of animals presenting adverse morphological effects (EC50), including craniofacial defects, was 5.2 μM for daily renewal exposure, and above this concentration, adverse behavioral effects were also observed in animals that followed a static exposure regimen. Thus, zebrafish data suggest that the developmental toxicity of pyriproxyfen may not be limited to insects.

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Section: Methodsmentioning

confidence: 99%

Assessment of the developmental and neurotoxicity of the mosquito control larvicide, pyriproxyfen, using embryonic zebrafish

Truong

Gonnerman

Simonich

et al. 2016

Environmental Pollution

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“…Currently, we have evaluated six Ru‐based anticancer compounds with these techniques (Côrte‐Real, Karas, Gírio, et al, ) (unpublished data). We believe this model could be a promising asset to high‐throughput evaluation of metal‐based anticancer compounds, particularly if coupled with new technologies including robotics to actualize whole organisms and automated chemical delivery systems (Truong et al, ; Wang et al, ). This becomes increasingly relevant as the literature regarding metallodrugs in modern clinical medicine and biochemical research continues to expand.…”

Section: Discussionmentioning

confidence: 99%

A novel screening method for transition metal‐based anticancer compounds using zebrafish embryo‐larval assay and inductively coupled plasma‐mass spectrometry analysis

Karas

Côrte-Real

Doherty

et al. 2019

J of Applied Toxicology

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As novel metallodrugs continue to emerge, they are evaluated using models, including zebrafish, that offer unique sublethal endpoints. Testing metal-based anticancer compounds with high-throughput zebrafish toxicological assays requires analytical methods with the sensitivity to detect these sublethal tissue doses in very small sample masses (e.g., egg mass 100 μg). A robust bioanalytical model, zebrafish embryos coupled with inductively coupled plasma-mass spectrometry (ICPMS) for measurement of delivered dose, creates a very effective means for screening metal-based chemotherapeutic agents. In this study, we used ICPMS quantitation with the zebrafish embryo assays to detect metal equivalents at multiple response endpoints for two compounds, the chemotherapeutic agent cisplatin and ruthenium (Ru)-based prospective metallodrug, PMC79. We hypothesized that cisplatin and PMC79 have different mechanisms for inducing apoptosis and result in similar lesions but different potencies following water-borne exposure. An ICPMS method was developed to detect the metal in waterborne solution and tissue (detection limit: 5 parts per trillion for Ru or platinum [Pt]). The Ru-based compound was more potent (LC 50 : 7.8 μM) than cisplatin (LC 50 : 158 μM) and induced disparate lesions. Lethality from cisplatin exposure exhibited a threshold (values >15 mg/L) while no threshold was observed for delayed hatching (lowest observed adverse effect level 3.75 mg/L cisplatin; 8.7Pt (ng)/organism). The Ru organometallic did not have a threshold for lethality.Cisplatin-induced delayed hatching was investigated further by larval-Pt distribution and preferentially distributed to the chorion. We propose that zebrafish embryolarval assays coupled with ICPMS serve as a powerful platform to evaluate relative potency and toxic effects of metallodrug candidates.

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“…48 At 6 hours post-fertilization (hpf), dechorinated zebrafish embryos ( n = 32) were exposed to different concentrations (ranging from 0.01 – 60 µM) of single OHPHE standards, mixture extracts formed by ELW1 at various time points, and reconstructed OHPHE standard mixtures. Briefly, embryos were dechorionated and exposed to 0 – 50 µM OHPHE standards (32 animals per concentration, 6 concentrations) from 6–120 hours post fertilization (hpf).…”

Section: Methodsmentioning

confidence: 99%

Formation of Developmentally Toxic Phenanthrene Metabolite Mixtures by Mycobacterium sp. ELW1

Schrlau

Kramer

Chlebowski

et al. 2017

Environ. Sci. Technol.

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Mycobacterium sp. ELW1 co-metabolically degraded up to 1.8 µmol phenanthrene (PHE) in ~48 hours (hr) and the formation of hydroxyphenanthrene (OHPHE) metabolites, including 1-hydroxyphenanthrene (1-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), 4-hydroxyphenanthrene (4-OHPHE), 9-hydroxyphenanthrene (9-OHPHE), 9,10-dihydroxyphenanthrene (1,9-OHPHE), and trans-9,10-dihydroxy-9,10-dihydrophenanthrene (trans-9,10-OHPHE), were identified and quantified over time. The monooxygenase responsible for co-metabolic transformation of PHE was inhibited by 1-octyne. First-order PHE transformation rates, kPHE, and half-lives, t1/2, for PHE-exposed cells ranged 0.16 – 0.51 hr−1 and 1.4 – 4.3 hr, respectively, and the 1-octyne controls ranged 0.015 – 0.10 hr−1 and 7.0 – 47 hr, respectively. While single compound standards of PHE and trans-9,10-OHPHE, the major OHPHE metabolite formed by ELW1, were not toxic to embryonic zebrafish (Danio rerio), single compound standards of minor OHPHE metabolites, 1-OHPHE, 3-OHPHE, 4-OHPHE, 9-OHPHE, and 1,9-OHPHE, were toxic, with effective concentrations (EC50s) ranging from 0.5– 5.5 µM. The metabolite mixtures formed by ELW1, and the reconstructed standard mixtures of the identified OHPHE metabolites, elicited a toxic response in zebrafish for the same 3 time points. EC50s for the metabolite mixtures formed by ELW1 were lower (more toxic) than those for the reconstructed standard mixtures of the identified OHPHE metabolites. Ten unidentified hydroxy PHE metabolites were measured in the derivatized mixtures formed by ELW1 and may explain the increased toxicity of the ELW1 metabolites mixture, relative to the reconstructed standard mixtures of the identified OHPHE metabolites.

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Optimizing multi-dimensional high throughput screening using zebrafish

Cited by 50 publications

References 27 publications

Assessment of the developmental and neurotoxicity of the mosquito control larvicide, pyriproxyfen, using embryonic zebrafish

Assessment of the developmental and neurotoxicity of the mosquito control larvicide, pyriproxyfen, using embryonic zebrafish

A novel screening method for transition metal‐based anticancer compounds using zebrafish embryo‐larval assay and inductively coupled plasma‐mass spectrometry analysis

Formation of Developmentally Toxic Phenanthrene Metabolite Mixtures by Mycobacterium sp. ELW1

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