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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
  • 75 Downloads

Abstract

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.

Keywords

: ABC transporters pxr Regulation Xenobiotics Metabolism Pharmaceutical Zebrafish 

Abbreviations

ABC transporters

adenosine triphosphate-binding cassette transporters

abcc1

adenosine triphosphate-binding cassette subfamily C member 1

abcb4

adenosine triphosphate-binding cassette subfamily B member 4

C

the control group

cDNA

complementary deoxyribonucleic acid

Ct

threshold cycle

cyp1a

cytochrome P450 family 1 subfamily A

cyp3a65

cytochrome P450 family 3 subfamily A polypeptide 65

DNA

deoxyribonucleic acid

ef1a

elongation factor 1 alpha

GOI

gene of interest

gst p2

glutathione-S-transferase type p2

H

high concentration of venlafaxine (30 μg/L)

hpf

hours post-fertilization

L

low concentration of venlafaxine (0.3 μg/L)

mRNA

messenger ribonucleic acid

pxr

pregnane X receptor

qPCR

real-time quantitative polymerase chain reaction

RNA

ribonucleic acid

RNAse

ribonuclease

SD

standard deviation

SNRI

serotonin and norepinephrine reuptake inhibitors

SSRI

selective serotonin reuptake inhibitors

UHPLC

ultra-high-performance liquid chromatography

WWTPs

wastewater treatment plants

Notes

Acknowledgments

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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