Phase II stanozolol metabolism study using the zebrafish water tank (ZWT) model

Matos, Rebecca Rodrigues; Anselmo, Carina de Souza; Sardela, Vinícius Figueiredo; Pereira, Henrique Marcelo Gualberto

doi:10.1016/j.jpba.2020.113886

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…The AFD leachate-treated embryos differentially expressed few genes from these classes; these only included cyp 21 a 2 (FC = 7.8), cyp 2 k 6 (FC = 7.4), ugt 5 a 2 (FC = 22.8), gsto 1 (FC = 2.0), and sult 2 st 3 (FC =1.8). In comparison, the AFP leachate-treated embryos exhibited regulation of 34 of 94 cyp genes, 11 of 45 ugt genes, , 5 of 27 gst genes, and 9 of 20 sult genes (Table S17). Presumably, the greater number of DEGs encoding biotransformation enzymes is a response to the 6-fold greater chemical complexity of the AFP leachate compared to that of the AFD leachate …”

Section: Resultsmentioning

confidence: 99%

Formulation Controls the Potential Neuromuscular Toxicity of Polyethylene Photoproducts in Developing Zebrafish

James

Karchner

Walsh

et al. 2023

Environ. Sci. Technol.

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Sunlight transforms plastic into water-soluble products, the potential toxicity of which remains unresolved, particularly for vertebrate animals. We evaluated acute toxicity and gene expression in developing zebrafish larvae after 5 days of exposure to photoproduced (P) and dark (D) leachates from additive-free polyethylene (PE) film and consumer-grade, additive-containing, conventional, and recycled PE bags. Using a "worst-case" scenario, with plastic concentrations exceeding those found in natural waters, we observed no acute toxicity. However, at the molecular level, RNA sequencing revealed differences in the number of differentially expressed genes (DEGs) for each leachate treatment: thousands of genes (5442 P, 577 D) for the additive-free film, tens of genes for the additive-containing conventional bag (14 P, 7 D), and none for the additive-containing recycled bag. Gene ontology enrichment analyses suggested that the additivefree PE leachates disrupted neuromuscular processes via biophysical signaling; this was most pronounced for the photoproduced leachates. We suggest that the fewer DEGs elicited by the leachates from conventional PE bags (and none from recycled bags) could be due to differences in photoproduced leachate composition caused by titanium dioxide-catalyzed reactions not present in the additive-free PE. This work demonstrates that the potential toxicity of plastic photoproducts can be product formulation-specific.

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Section: Resultsmentioning

confidence: 99%

Formulation Controls the Potential Neuromuscular Toxicity of Polyethylene Photoproducts in Developing Zebrafish

James

Karchner

Walsh

et al. 2023

Environ. Sci. Technol.

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“…Based on the comparable outcomes, medaka embryos could serve as an alternative model to identify potential metabolites for human biotransformation of doping-relevant compounds. In the past few years, a couple of studies investigated the zebrafish ( Danio rerio ) as species to model human metabolism of different doping-related compound classes (e.g., anabolic steroids, stimulants, cannabimimetics, secretagogues) (de Souza Anselmo et al 2017; Sardela et al 2018 , 2020 ; Matos et al 2021 ). The so-called zebrafish water tank model seems to be a promising model for metabolism studies.…”

Section: Discussionmentioning

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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“…Matos et al studied the metabolism of stanozolol using ZWT experimental setup. The study showed the detection of ten metabolites after 8 h of experiment, four hydroxylated sulfates and six glucuronide metabolites as 3 OH-stanzolol-glucuronide, 16ß-OH-stanozolol-glucuronide, 17epi-stanozolol-Nglucuronide and stanozolol-O-glucuronide [160].…”

Section: Expanding the Window Detection Of Exogenous Aas For Itp And ...mentioning

confidence: 97%

Olympic Anti-Doping Laboratory: The Analytical Technological Road From 2016 Rio De Janeiro to 2021 Tokyo

et al. 2021

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The summer Olympic Games is the major mega sports event since the first modern era Olympiad, held in Athens, Greece in 1896. International Olympic Committee (IOC) has the responsibility of the organization of the summer and winter Games ensuring the broadcast in all corners of earth. The World Anti-Doping Agency (WADA) is the responsible organization of the fight against doping in sports. IOC and WADA support the event's country WADA Accredited Laboratory to incorporate the maximum of the new analytical technologies to become applicable during the event's antidoping testing. The current study reviewed the last 5 years progresses of the antidoping system with emphasis on the laboratory field.

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Phase II stanozolol metabolism study using the zebrafish water tank (ZWT) model

Cited by 8 publications

References 23 publications

Formulation Controls the Potential Neuromuscular Toxicity of Polyethylene Photoproducts in Developing Zebrafish

Formulation Controls the Potential Neuromuscular Toxicity of Polyethylene Photoproducts in Developing Zebrafish

Medaka embryos as a model for metabolism of anabolic steroids

Olympic Anti-Doping Laboratory: The Analytical Technological Road From 2016 Rio De Janeiro to 2021 Tokyo

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