ArticleBMC pharmacology & toxicology2017
Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos.
Article in BMC pharmacology & toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
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- Effect of terbutaline plus doxofylline on chronic obstructive pulmonary disease.American journal of translational research · 2021Article
- Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors.Frontiers in pharmacology · 2020Review
- Methylxanthines: Potential Therapeutic Agents for Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2019Article
- Zebrafish Larvae as a Behavioral Model in Neuropharmacology.Biomedicines · 2019Review
- Diprophylline inhibits non-small cell lung cancer A549 cell proliferation and migration, and promotes apoptosis, by downregulating PI3K signaling pathway.Oncology letters · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundZebrafish embryos are emerging as a model for pharmacological and toxicological studies. We used zebrafish embryos to study the general toxicity and cardiovascular effects of eight methylxanthines: aminophylline, caffeine, diprophylline, doxofylline, etophylline, 3-isobutyl-1-methylxanthine (IBMX), pentoxifylline and theophylline.
methodsMicroinjections of the eight methylxanthines were performed in 1-2 cell stage zebrafish embryos and the general toxicity and cardiovascular effects were analyzed at different time points. Embryotoxicity and teratogenicity were evaluated to understand the general toxicity of these compounds. Structural and functional alterations of the heart were evaluated to assess the cardiovascular effects.
resultsOur results showed different activity patterns of the methylxanthines drugs. Caffeine, IBMX, pentoxifylline and theophylline were highly embryotoxic and teratogenic; aminophylline, doxofylline and etophylline were embryotoxic and teratogenic only at higher doses, and diprophylline showed a minimal (<10%) embryotoxicity and teratogenicity. Most of these drugs induced structural alteration of the heart in 20-40% of the injected embryos with the maximum dose. This structural alteration was fatal with the embryos ultimately dying within 120 hpf. All the drugs induced a transient increase in heart rate at 48 hpf which returned to baseline within 96 hpf. This functional effect of methylxanthines showed similarity to the studies done in humans and other vertebrates.
conclusionOur results indicate the potential toxicity and teratogenicity of different methylxanthines in the embryos during embryonic development, the most sensitive period of life. Although interspecies differences need to be considered before drawing any conclusion, our study elucidated that a single exposure of methylxanthines at therapeutic range could induce cardiac dysfunction besides causing embryotoxicity and teratogenicity. Of all the drugs, diprophylline appeared to be safer, with lower degree of embryotoxicity, teratogenicity and cardiac toxicity as compared to other methylxanthines.
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