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Research article2018Peer reviewed

Effect of human pharmaceuticals common to aquatic environments on hepatic CYP1A and CYP3A-like activities in rainbow trout (Oncorhynchus mykiss): An in vitro study

Burkina, Viktoriia; Sakalli, Sidika; Pilipenko, Nadezhda; Zlabek, Vladimir; Zamaratskaia, Galia

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

          • Sustainable Development Goals

          SDG6 Ensure availability and sustainable management of water and sanitation for all
          SDG3 Ensure healthy lives and promote well-being for all at all ages

          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