Comprehensive Zebrafish Water Tank Experiment for Metabolic Studies of Testolactone

Sardela, Vinícius Figueiredo; Sardela, P.D.O.; Lisboa, Raïssa R; Matias, Bernardo Fonseca; Anselmo, Carina de Souza; Carvalho, Aline Reis de; Nunes, Isabele K C; Padilha, Marina; Neto, Francisco Radler de Aquino; Pereira, Henrique Marcelo Gualberto

doi:10.1089/zeb.2019.1791

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…The capability of a zebrafish model to mimic human metabolic reactions concerning testolactone was assessed by Sardela et al, who solubilized 1 mg of testolactone in a 4‐L water tank containing 18 zebrafishes and sampled tank water up to 168 hr. The formation of 4,5‐dihydrotestolactone and 1,2,4,5‐tetrahydrotestolactone as well as an increased concentration of T and androstenedione was determined by LC‐HRMS, suggesting that the animal model could be a valuable tool in studying steroid metabolic reactions for doping control purposes 141 . Biotransformation products of another steroidal aromatase inhibitor referred to as arimistane were investigated by Martinez Brito et al 142 Here, three study participants orally ingested 25 mg of arimistane, and urine samples were collected prior to and up to 95 hr post‐administration for subsequent GC‐QqQ‐ and GC‐Q/TOF‐MS analysis to probe for a potential influence of arimistane on the steroid profile as well as arimistane‐specific target analytes.…”

Section: Hormone and Metabolic Modulatorsmentioning

confidence: 99%

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

Thevis

Kuuranne

Geyer

2020

Drug Testing and Analysis

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Analytical chemistry-based research in sports drug testing has been a dynamic endeavor for several decades, with technology-driven innovations continuously contributing to significant improvements in various regards including analytical sensitivity, comprehensiveness of target analytes, differentiation of natural/ endogenous substances from structurally identical but synthetically derived compounds, assessment of alternative matrices for doping control purposes, and so forth. The resulting breadth of tools being investigated and developed by anti-doping researchers has allowed to substantially improve anti-doping programs and data interpretation in general. Additionally, these outcomes have been an extremely valuable pledge for routine doping controls during the unprecedented global health crisis that severely affected established sports drug testing strategies. In this edition of the annual banned-substance review, literature on recent developments in antidoping published between October 2019 and September 2020 is summarized and discussed, particularly focusing on human doping controls and potential applications of new testing strategies to substances and methods of doping specified the World Anti-Doping Agency's 2020 Prohibited List.

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Section: Hormone and Metabolic Modulatorsmentioning

confidence: 99%

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

Thevis

Kuuranne

Geyer

2020

Drug Testing and Analysis

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“…Fishes are often described as “lower” vertebrates, ignoring their evolutionary success and their typical vertebrate bauplan. A fish model investigated for biotransformation studies of different compound classes with doping-relevance is the zebrafish ( Danio rerio ) (de Souza Anselmo et al 2017 ; Sardela et al 2018 , 2020 ). In the so-called zebrafish water tank (ZWT) approach, test compounds are applied to the adult fish by solubilisation in the tank water.…”

Section: Introductionmentioning

confidence: 99%

Medaka embryos as a model for metabolism of anabolic steroids

et al. 2022

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In anti-doping science, the knowledge of drug metabolism is a prerequisite to identify analytical targets for the detection of misused prohibited substances. As the most obvious way to study xenobiotic metabolism, the administration to human volunteers, faces ethical concerns, there is a need for model systems. In the present study, we investigated whether Oryzias latipes (medaka) embryos might be an alternative, non-animal test model to study human-like metabolism. In the present study, we exposed medaka embryos at the morula stage to the anabolic steroid metandienone (10 µM or 50 µM) for a period of 2 or 8 days. According to the fish embryo toxicity test (OECD test), we assessed the developmental status of the embryos. We further investigated metandienone metabolites by high-performance liquid chromatography- and gas chromatography-mass spectrometry. Medaka embryos produced three mono-hydroxylated and one reduced metabolite known from human biotransformation. Developmental malformations were observed for the exposition to 50 µM metandienone, while a significant elevation of the heart beat was also present in those individuals exposed to the lower dose for 8 days. The present study demonstrates that the medaka embryo represents a promising model to study human-like metabolism. Moreover, the judgement of developmental parameters of the fish embryos enables for the simultaneous assessment of toxicity.

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“…In vivo models such as rodents are more expensive, do not allow for high throughput experiments, and are time‐consuming. The zebrafish model is a popular, cost‐effective, and high throughput model used to study drug toxicity and metabolism due to their similarities to human (de Souza Anselmo et al, 2017; Gamse & Gorelick, 2016; Jones et al, 2012; Matos et al, 2020; Prado et al, 2021; Sardela et al, 2020). The organization for economic cooperation and development (OECD) developed guidelines for testing acute or lethal toxicity of chemicals on zebrafish larvae and listed the endpoints as coagulation, lack of somite formation, lack of tail detachment from the yolk sac, and lack of heartbeat (OECD, 2013).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of fentanyl toxicity and metabolism using a zebrafish model

Cooman

Bergeron

Coltogirone

et al. 2021

J of Applied Toxicology

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The increased abuse of novel drugs has created a critical need for cheap and rapid in vivo models to understand whole organism drug‐induced toxicity and metabolic impacts. One such model is zebrafish, which share many similarities to human. Assays have been developed for behavioral, toxicity, and metabolism elucidation following chemical exposure. The zebrafish model provides the advantage of assessing these parameters within a single study. Previous zebrafish studies have evaluated the behavioral effects of fentanyl, but not developmental toxicity and its relation to metabolism. In this study, we evaluate the effects of fentanyl on the development of wild‐type (TL strain) zebrafish and its metabolism over 4 days. Fertilized eggs were exposed to six concentrations of fentanyl (0.01, 0.1, 1, 10, 50, and 100 μM) through embryo media incubated at 28–29°C. Observations included egg coagulation, somite formation, heartbeat, tail and yolk morphology, pericardial formation, and swim bladder inflation. The incubation media was analyzed for the presence of metabolites using a targeted metabolomics approach. Fentanyl concentration caused significant effects on survival and development, with notable defects to the tail, yolk, and pericardium at 50 and 100 μM. Despropionyl fentanyl (4‐ANPP), β‐hydroxy fentanyl, and norfentanyl were detected in zebrafish larvae. We present a single in vivo model to assess toxicity and metabolism of fentanyl exposure in a vertebrate model system. Our findings provide a foundation for further investigations into fentanyl's mechanism of action and translation to human drug exposure.

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Comprehensive Zebrafish Water Tank Experiment for Metabolic Studies of Testolactone

Cited by 7 publications

References 20 publications

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

Medaka embryos as a model for metabolism of anabolic steroids

Evaluation of fentanyl toxicity and metabolism using a zebrafish model

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