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

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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.

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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

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Acknowledgments

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

Funding

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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Authors and Affiliations

  1. Department of Animal Protection, Welfare and Behaviour, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho tr. 1946/1, 612 42, Brno, Czech Republic

    Nikola Hodkovicova, Pavla Sehonova, Jana Blahova, Petr Marsalek, Radka Dobsikova, Vladimir Vecerek & Zdenka Svobodova

  2. Department of Immunology, Veterinary Research Institute, Hudcova 296/70, 621 00, Brno, Czech Republic

    Nikola Hodkovicova, Martin Faldyna & Monika Vicenova

  3. Department of Veterinary Public Health and Forensic Medicine, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho tr. 1946/1, 612 42, Brno, Czech Republic

    Pavla Sehonova, Premysl Mikula, Petr Chloupek & Petra Vosmerova

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  1. Nikola Hodkovicova
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  2. Pavla Sehonova
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  12. Zdenka Svobodova
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Correspondence to Nikola Hodkovicova.

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Highlights

• The effect of aquatic pollutant venlafaxine on Danio rerio was studied in dose- and time-dependent manner.

• The impact on gene expression of genes involved in xenobiotic biotransformation and correlation with pxr gene was investigated.

• The downregulation at 96 hpf and upregulation of gene expression at 144 hpf was observed for both tested concentrations.

The pxr regulative function seems to be disrupted after exposure to venlafaxine.

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Hodkovicova, N., Sehonova, P., Blahova, J. et al. The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos. Environ Sci Pollut Res 27, 1686–1696 (2020). https://doi.org/10.1007/s11356-019-06726-2

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