Burkina, Viktoriia
- University of South Bohemia in České Budějovice
Abstract
This study examined the ability of several human pharmaceuticals to modulate hepatic piscine CYP-mediated monooxygenase activities. Effects of six pharmaceuticals: diclofenac, sulfamethoxazole, tramadol, carbamazepine, venlafaxine and nefazodone, were investigated in vitro in rainbow trout hepatic microsomes. The reactions of 7-ethoxyresorufin-O-deethylase (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylase (BFCOD), were used as markers for hepatic CYP1A and CYP3A-like activities, respectively. Our results showed that EROD and BFCOD activities were both affected by nefazodone. Nefazodone inhibited EROD in a dose dependent manner and was found to be a potent non-competitive inhibitor of EROD with a K-i value of 6.6 mu M. BFCOD activity was inhibited noncompetitively in the presence of nefazadone with K-i value of 30.7 mu M. BFCOD activity was slightly reduced only by the highest concentration of carbamazepine. Diclofenac, sulfamethoxazole, tramadol, and venlafaxine did not affect the activity of either EROD or BFCOD. We further exposed microsomal fraction to mixtures of six pharmaceuticals to investigate potential inhibition. The results showed that EROD and BFCOD activity was inhibited on 94% and 80%, respectively at higher tested concentration. To our knowledge, this is the first report to demonstrate an inhibitory effect of nefazodone on hepatic CYP1A and CYP3A-like proteins in rainbow trout. (C) 2018 Elsevier Ltd. All rights reserved.
Keywords
Fish microsomes; Cytochrome P450; Inhibition; Mixture of compounds; Antidepressant
Published in
Chemosphere
2018, volume: 205, pages: 380-386
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
SLU Authors
Pilipenko, Nadezhola
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
Zlabek, Vladimir
- University of South Bohemia in České Budějovice
Zamaratskaia, Galia
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
- University of South Bohemia in České Budějovice
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
Global goals (SDG)
SDG3 Good health and well-being
SDG6 Clean water and sanitation
UKÄ Subject classification
Oceanography, Hydrology, Water Resources
Publication identifier
- DOI: https://doi.org/10.1016/j.chemosphere.2018.04.080
Permanent link to this page (URI)
https://res.slu.se/id/publ/96194