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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Mar 12

PMID 28282918

Citations 15

Authors

Ram Manohar Basnet

Michela Guarienti

Maurizio Memo

Affiliations

Soon will be listed here.

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 (TC) calculated in zebrafish embryos and lethal doses (LD) 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.

Citing Articles

Knockdown Induces Obesity and AHO Features in Early Zebrafish Larvae.

Abbas A, Hammad A, Zakaria Z, Al-Asmakh M, Hussain K, Al-Shafai M Int J Mol Sci. 2024; 25(23).

PMID: 39684386 PMC: 11641299. DOI: 10.3390/ijms252312674.

Developmental Neurotoxicity of Difenoconazole in Zebrafish Embryos.

Yang Q, Deng P, Xing D, Liu H, Shi F, Hu L Toxics. 2023; 11(4).

PMID: 37112580 PMC: 10142703. DOI: 10.3390/toxics11040353.

Bi-Allelic Mutations in Zebrafish Gene Lead to Testicular Atrophy and Perturbed Behavior without Signs of Neurodegeneration.

Mignani L, Zizioli D, Khatri D, Facchinello N, Schiavone M, De Palma G Int J Mol Sci. 2022; 23(21).

PMID: 36361705 PMC: 9657214. DOI: 10.3390/ijms232112914.

MiR92b-3p synthetic analogue impairs zebrafish embryonic development, leading to ocular defects, decreased movement and hatching rate, and increased mortality.

Kranert K, Wozny M, Podlasz P, Wasowicz K, Brzuzan P J Appl Genet. 2022; 64(1):145-157.

PMID: 36274083 PMC: 9837005. DOI: 10.1007/s13353-022-00732-w.

Fabrication and characterization of Agarwood extract-loaded nanocapsules and evaluation of their toxicity and anti-inflammatory activity on RAW 264.7 cells and in zebrafish embryos.

Eissa M, Hashim Y, Mohd Nasir M, Nor Y, Salleh H, Md Isa M Drug Deliv. 2021; 28(1):2618-2633.

PMID: 34894947 PMC: 8676596. DOI: 10.1080/10717544.2021.2012307.

References

Olivares C, Field J, Simonich M, Tanguay R, Sierra-Alvarez R . Arsenic (III, V), indium (III), and gallium (III) toxicity to zebrafish embryos using a high-throughput multi-endpoint in vivo developmental and behavioral assay. Chemosphere. 2016; 148:361-8. PMC: 4754138. DOI: 10.1016/j.chemosphere.2016.01.050. View

Onatibia-Astibia A, Martinez-Pinilla E, Franco R . The potential of methylxanthine-based therapies in pediatric respiratory tract diseases. Respir Med. 2016; 112:1-9. DOI: 10.1016/j.rmed.2016.01.022. View

Raldua D, Pina B . In vivo zebrafish assays for analyzing drug toxicity. Expert Opin Drug Metab Toxicol. 2014; 10(5):685-97. DOI: 10.1517/17425255.2014.896339. View

Nagel R . DarT: The embryo test with the Zebrafish Danio rerio--a general model in ecotoxicology and toxicology. ALTEX. 2002; 19 Suppl 1:38-48. View

Tran T, Sneed B, Haider J, Blavo D, White A, Aiyejorun T . Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish. Cancer Res. 2007; 67(23):11386-92. DOI: 10.1158/0008-5472.CAN-07-3126. View

Lantz-McPeak S, Guo X, Cuevas E, Dumas M, Newport G, Ali S . Developmental toxicity assay using high content screening of zebrafish embryos. J Appl Toxicol. 2014; 35(3):261-72. PMC: 4957247. DOI: 10.1002/jat.3029. View

DE Sarro A, Grasso S, Zappala M, Nava F, De Sarro G . Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats. Naunyn Schmiedebergs Arch Pharmacol. 1997; 356(1):48-55. DOI: 10.1007/pl00005027. View

Guarienti M, Giacopuzzi E, Gianoncelli A, Sigala S, Spano P, Pecorelli S . Computational and functional analysis of biopharmaceutical drugs in zebrafish: Erythropoietin as a test model. Pharmacol Res. 2015; 102:12-21. DOI: 10.1016/j.phrs.2015.09.004. View

Stablein J, Samaan S, BUKANTZ S, Lockey R . Pharmacokinetics and bioavailability of three dyphylline preparations. Eur J Clin Pharmacol. 1983; 25(2):281-3. DOI: 10.1007/BF00543805. View

10.

Stewart A, Desmond D, Kyzar E, Gaikwad S, Roth A, Riehl R . Perspectives of zebrafish models of epilepsy: what, how and where next?. Brain Res Bull. 2011; 87(2-3):135-43. DOI: 10.1016/j.brainresbull.2011.11.020. View

11.

Page C . Doxofylline: a "novofylline". Pulm Pharmacol Ther. 2010; 23(4):231-4. DOI: 10.1016/j.pupt.2010.04.002. View

12.

Sotelo A, Soleri D, Wacher C, Sanchez-Chinchillas A, Argote R . Chemical and nutritional composition of tejate, a traditional maize and cacao beverage from the Central Valleys of Oaxaca, Mexico. Plant Foods Hum Nutr. 2012; 67(2):148-55. DOI: 10.1007/s11130-012-0281-5. View

13.

Yokoyama H, Onodera K, Yagi T, Iinuma K . Therapeutic doses of theophylline exert proconvulsant effects in developing mice. Brain Dev. 1997; 19(6):403-7. DOI: 10.1016/s0387-7604(97)00051-x. View

14.

Ali S, Champagne D, Richardson M . Behavioral profiling of zebrafish embryos exposed to a panel of 60 water-soluble compounds. Behav Brain Res. 2011; 228(2):272-83. DOI: 10.1016/j.bbr.2011.11.020. View

15.

Kukovetz W, Poch G, Holzmann S . Overadditive synergism between theophylline, diprophylline and proxyphylline in tracheal smooth muscle relaxation. Arzneimittelforschung. 1983; 33(10):1450-4. View

16.

Franco R, Onatibia-Astibia A, Martinez-Pinilla E . Health benefits of methylxanthines in cacao and chocolate. Nutrients. 2013; 5(10):4159-73. PMC: 3820066. DOI: 10.3390/nu5104159. View

17.

Afrikanova T, Serruys A, Buenafe O, Clinckers R, Smolders I, de Witte P . Validation of the zebrafish pentylenetetrazol seizure model: locomotor versus electrographic responses to antiepileptic drugs. PLoS One. 2013; 8(1):e54166. PMC: 3544809. DOI: 10.1371/journal.pone.0054166. View

18.

Knobel M, Busser F, Rico-Rico A, Kramer N, Hermens J, Hafner C . Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis. Environ Sci Technol. 2012; 46(17):9690-700. DOI: 10.1021/es301729q. View

19.

McKeown K, Downes G, Hutson L . Modular laboratory exercises to analyze the development of zebrafish motor behavior. Zebrafish. 2009; 6(2):179-85. PMC: 2765818. DOI: 10.1089/zeb.2008.0564. View

20.

Guarienti M, Gianoncelli A, Bontempi E, Cardozo S, Borgese L, Zizioli D . Biosafe inertization of municipal solid waste incinerator residues by COSMOS technology. J Hazard Mater. 2014; 279:311-21. DOI: 10.1016/j.jhazmat.2014.07.017. View