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Int. J. Mol. Sci. 2017, 18(3), 596; doi:10.3390/ijms18030596

Zebrafish Embryo as an In Vivo Model for Behavioral and Pharmacological Characterization of Methylxanthine Drugs

Department of Molecular and Translational Medicine, University of Brescia, Viale Europa, 11, 25123 Brescia, Italy
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Academic Editor: Juliette Legler
Received: 6 February 2017 / Revised: 1 March 2017 / Accepted: 6 March 2017 / Published: 9 March 2017
(This article belongs to the Special Issue Zebrafish: A Model for Toxicological Research)
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Abstract

Zebrafish embryo is emerging as an important tool for behavior analysis as well as toxicity testing. In this study, we compared the effect of nine different methylxanthine drugs using zebrafish embryo as a model. We performed behavioral analysis, biochemical assay and Fish Embryo Toxicity (FET) test in zebrafish embryos after treatment with methylxanthines. Each drug appeared to behave in different ways and showed a distinct pattern of results. Embryos treated with seven out of nine methylxanthines exhibited epileptic-like pattern of movements, the severity of which varied with drugs and doses used. Cyclic AMP measurement showed that, despite of a significant increase in cAMP with some compounds, it was unrelated to the observed movement behavior changes. FET test showed a different pattern of toxicity with different methylxanthines. Each drug could be distinguished from the other based on its effect on mortality, morphological defects and teratogenic effects. In addition, there was a strong positive correlation between the toxic doses (TC50) calculated in zebrafish embryos and lethal doses (LD50) in rodents obtained from TOXNET database. Taken together, all these findings elucidate the potentiality of zebrafish embryos as an in vivo model for behavioral and toxicity testing of methylxanthines and other related compounds. View Full-Text
Keywords: methylxanthine; zebrafish embryos; behavior; movement; cyclic AMP; Fish Embryo Toxicity test methylxanthine; zebrafish embryos; behavior; movement; cyclic AMP; Fish Embryo Toxicity test
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Basnet, R.M.; Guarienti, M.; Memo, M. Zebrafish Embryo as an In Vivo Model for Behavioral and Pharmacological Characterization of Methylxanthine Drugs. Int. J. Mol. Sci. 2017, 18, 596.

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