Evaluation of β-adrenergic ligands for development of pharmacological heart failure and transparency models in zebrafish

Maciąg, Monika; Wnorowski, Artur; Bednarz, Kinga; Płazińska, Anita

doi:10.1016/j.taap.2021.115812

Cited by 11 publications

(6 citation statements)

References 68 publications

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“…The toxicity of chemical substances was evaluated using zebrafish embryos, based on OECD Guidelines for the Testing of Chemicals [10] with modifications according to Macig and co-authors [36,37]. To minimize delays, a minimum of 40 embryos were randomly selected for each treatment group and transferred to a 6-well plate containing 2 mL of either nicotine, cytisine, a combination of both drugs, or a selected concentration.…”

Section: Chemical Treatmentmentioning

confidence: 99%

Nicotine and Cytisine Embryotoxicity in the Experimental Zebrafish Model

Świątkowski

Budzyńska

Maciąg

et al. 2023

IJMS

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Tobacco smoking is one of the most serious health problems. Potentially lethal effects of nicotine for adults can occur with as little as 30 to 60 mg, although severe symptoms can arise with lower doses. Furthermore, the route of administration also influences the toxicity. Cytisine is one of the most popular medications in nicotinism treatment. Like nicotine, cytisine is a plant alkaloid, signaling through nicotinic acetylcholine receptors. Our study evaluated the effects of cytisine in nicotine-induced embryotoxic effects using zebrafish larvae. We examined the teratogenicity of nicotine and cytisine alone or in combination. Nicotine increased mortality and delayed hatching of zebrafish larvae in a dose-dependent manner. Cytisine did not affect mortality in a wide range of concentrations, and hatching delay was observed only at the highest concentrations, above 2 mM. Administering compounds together partially reduced the adverse teratogenic effect induced by nicotine alone. The protective effect of cytisine against the nicotine effect, observed in zebrafish, will contribute to future studies or treatments related to nicotine addiction or prenatal nicotine exposure in humans.

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Section: Chemical Treatmentmentioning

confidence: 99%

Nicotine and Cytisine Embryotoxicity in the Experimental Zebrafish Model

Świątkowski

Budzyńska

Maciąg

et al. 2023

IJMS

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“…Zebrafish are emerging as popular model organisms for understanding heart function, including the effects of ß‐adrenergic stimulation 15–20 . Owing to a third whole‐genome duplication event in early teleost fishes, zebrafish are endowed with a bolstered array of adrb genes: adrb1 , adrb2a , adrb2b , adrb3a , and adrb3b 2,21 .…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14] Zebrafish are emerging as popular model organisms for understanding heart function, including the effects of ß-adrenergic stimulation. [15][16][17][18][19][20] Owing to a third wholegenome duplication event in early teleost fishes, zebrafish are endowed with a bolstered array of adrb genes: adrb1, adrb2a, adrb2b, adrb3a, and adrb3b. 2,21 Evidently, the "second" adrb1 gene was lost, presumably as it was redundant; such "nonfunctionalization" is a common fate of duplicated genes.…”

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confidence: 99%

Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish

et al. 2022

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Aim Although zebrafish are gaining popularity as biomedical models of cardiovascular disease, our understanding of their cardiac control mechanisms is fragmentary. Our goal was to clarify the controversial role of the ß1‐adrenergic receptor (AR) in the regulation of heart rate in zebrafish. Methods CRISPR‐Cas9 was used to delete the adrb1 gene in zebrafish allowing us to generate a stable adrb1−/− line. Larval heart rates were measured during pharmacological protocols and with exposure to hypercapnia. Expression of the five zebrafish adrb genes were measured in larval zebrafish hearts using qPCR. Results Compared with genetically matched wild‐types (adrb1+/+), adrb1−/− larvae exhibited ~20 beats min−1 lower heart rate, measured from 2 to 21 days post‐fertilization (dpf). Nevertheless, adrb1−/− larvae exhibited preserved positive chronotropic responses to pharmacological treatment with AR agonists (adrenaline, noradrenaline, isoproterenol), which were blocked by propranolol (general ß‐AR antagonist). Regardless of genotype, larvae exhibited similar increases in heart rate in response to hypercapnia (1% CO2) at 5 dpf, but tachycardia was blunted in adrb1−/− larvae at 6 dpf. adrb1 gene expression was abolished in the hearts of adrb1−/− larvae, confirming successful knockout. While gene expression of adrb2a and adrb3a was unchanged, adrb2b and adrb3b mRNA levels increased in adrb1−/− larval hearts. Conclusion Despite adrb1 contributing to the setting of resting heart rate in larvae, it is not strictly essential for zebrafish, as we generated a viable and breeding adrb1−/− line. The chronotropic effects of adrenergic stimulation persist in adrb1−/− zebrafish, likely due to the upregulation of other ß‐AR subtypes.

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“…Zebrafish ( Danio rerio ) are increasingly used in metabolic studies, and are an invaluable model organism for developmental research, featuring a rapid generation time, large spawn size, genetic tractability, and transparent embryos ( Howe et al, 2013 ). Zebrafish are also a growing model for cardiac research ( Maciag et al, 2022 ) and in many cases, metabolism is used as an index for cardiac performance (e.g., Nyboer and Chapman, 2018 ). There is also a body of literature incorporating metabolism and cardiac function into developmental studies and environmental/climate change related studies with zebrafish ( Seth et al, 2013 ; Roy et al, 2017 ; Dhillon et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%