The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos

  • Nikola HodkovicovaEmail author
  • Pavla Sehonova
  • Jana Blahova
  • Martin Faldyna
  • Petr Marsalek
  • Premysl Mikula
  • Petr Chloupek
  • Radka Dobsikova
  • Vladimir Vecerek
  • Monika Vicenova
  • Petra Vosmerova
  • Zdenka Svobodova
Research Article


The effect of venlafaxine, a pharmaceutical commonly found in aquatic environment, was analyzed on non-target organism, Danio rerio (Hamilton, 1822). D. rerio embryos were treated by two different concentrations of venlafaxine: either concentration relevant in aquatic environment (0.3 μg/L) or concentration that was two orders of magnitude higher (30 μg/L) for the evaluation of dose-dependent effect. Time-dependent effect was rated at 24, 96, and 144 h post-fertilization (hpf). For gene expression, genes representing one of the phases of xenobiotic biotransformation (0 to III) were selected. The results of this study showed that the effect of venlafaxine on the zebrafish embryos is the most evident at hatching (96 hpf). At this time, the results showed a downregulation of gene expression in each phase of biotransformation and in both tested concentrations. In contrast, an upregulation of most of the genes was observed 144 hpf for both tested venlafaxine concentrations. The study shows that venlafaxine can affect the gene expression of biotransformation enzymes in D. rerio embryos even in the environmentally relevant concentration and thus disrupt the process of biotransformation. Moreover, the pxr regulation of genes seems to be disrupted after venlafaxine exposure in dose- and time-dependent manner.


: ABC transporters pxr Regulation Xenobiotics Metabolism Pharmaceutical Zebrafish 


ABC transporters

adenosine triphosphate-binding cassette transporters


adenosine triphosphate-binding cassette subfamily C member 1


adenosine triphosphate-binding cassette subfamily B member 4


the control group


complementary deoxyribonucleic acid


threshold cycle


cytochrome P450 family 1 subfamily A


cytochrome P450 family 3 subfamily A polypeptide 65


deoxyribonucleic acid


elongation factor 1 alpha


gene of interest

gst p2

glutathione-S-transferase type p2


high concentration of venlafaxine (30 μg/L)


hours post-fertilization


low concentration of venlafaxine (0.3 μg/L)


messenger ribonucleic acid


pregnane X receptor


real-time quantitative polymerase chain reaction


ribonucleic acid




standard deviation


serotonin and norepinephrine reuptake inhibitors


selective serotonin reuptake inhibitors


ultra-high-performance liquid chromatography


wastewater treatment plants



The authors would like to thank Mrs. Ludmila Faldikova for the English correction.

Funding information

This work was supported by the Internal Grant Agency of the University of Veterinary and Pharmaceutical Sciences Brno [202/2017/FVHE, 2017], by the Ministry of Education, Youth and Sports of the Czech Republic [LO1218], and by the ERDF/ESF “Profish” [no. CZ.02.1.01/0.0/0.0/16_019/0000869].


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Nikola Hodkovicova
    • 1
    • 2
    Email author
  • Pavla Sehonova
    • 1
    • 3
  • Jana Blahova
    • 1
  • Martin Faldyna
    • 2
  • Petr Marsalek
    • 1
  • Premysl Mikula
    • 3
  • Petr Chloupek
    • 3
  • Radka Dobsikova
    • 1
  • Vladimir Vecerek
    • 1
  • Monika Vicenova
    • 2
  • Petra Vosmerova
    • 3
  • Zdenka Svobodova
    • 1
  1. 1.Department of Animal Protection, Welfare and Behaviour, Faculty of Veterinary Hygiene and EcologyUniversity of Veterinary and Pharmaceutical Sciences BrnoBrnoCzech Republic
  2. 2.Department of ImmunologyVeterinary Research InstituteBrnoCzech Republic
  3. 3.Department of Veterinary Public Health and Forensic Medicine, Faculty of Veterinary Hygiene and EcologyUniversity of Veterinary and Pharmaceutical Sciences BrnoBrnoCzech Republic

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