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Research article - Peer-reviewed, 2020

In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio)

Burkina, Viktoriia; Sakalli, Sidika; Pham Thai Giang; Grabicova, Katerina; Stanova, Andrea Vojs; Zamaratskaia, Galia; Zlabek, Vladimir

Abstract

Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to produce the main metabolites from citalopram, metoprolol, sertraline, and venlafaxine. Metabolism in fish S9 fractions was compared to that in sheep. The metabolism of citalopram was further studied in fish. Our results suggest a large difference in the rate of metabolites formation between fish and sheep. Fish hepatic S9 fractions do not show an ability to form metabolites from venlafaxine, which was also the case for sheep. Citalopram, metoprolol, and sertraline were metabolized by both fish and sheep S9. Citalopram showed concentration-dependent N-desmethylcitalopram formation with V-max = 1781 pmol/min/mg and K-m = 29.7 mu M. The presence of ellipticine, a specific CYP1A inhibitor, in the incubations reduced the formation of N-desmethylcitalopram by 30-100% depending on the applied concentration. These findings suggest that CYP1A is the major enzyme contributing to the formation of N-desmethylcitalopram. In summary, the results from the present in vitro study suggest that common carp can form the major metabolites of citalopram, metoprolol, and sertraline.

Keywords

cytochrome P450; metabolite formation; citalopram; sertraline; venlafaxine; metoprolol; environmental toxicology

Published in

Molecules (Basel, Switzerland)
2020, volume: 25, number: 11, article number: 2690
Publisher: MDPI

Authors' information

Burkina, Viktoriia
University of South Bohemia in České Budějovice
Burkina, Viktoriia
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Sakalli, Sidika
Univ South Bohemia Ceske Budejovice
Giang, Pham Thai
University of South Bohemia in České Budějovice
Grabicova, Katerina
Univ South Bohemia Ceske Budejovice
Stanova, Andrea Vojs
Comenius Univ
Swedish University of Agricultural Sciences, Department of Molecular Sciences
University of South Bohemia in České Budějovice
Zlabek, Vladimir
Univ South Bohemia Ceske Budejovice

UKÄ Subject classification

Biochemistry and Molecular Biology
Environmental Sciences

Publication Identifiers

DOI: https://doi.org/10.3390/molecules25112690

URI (permanent link to this page)

https://res.slu.se/id/publ/107205