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

Burkina, Viktoriia and Sakalli, Sidika and Giang, Pham Thai and Grabicova, Katerina and Stanova, Andrea Vojs and Zamaratskaia, Galia and Zlabek, Vladimir (2020). In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio). Molecules (Basel, Switzerland). 25 , 2690 , 1-11
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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.

Authors/Creators:Burkina, Viktoriia and Sakalli, Sidika and Giang, Pham Thai and Grabicova, Katerina and Stanova, Andrea Vojs and Zamaratskaia, Galia and Zlabek, Vladimir
Title:In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio)
Year of publishing :2020
Volume:25
Article number:2690
Number of Pages:11
Publisher:MDPI
Language:English
Publication Type:Journal article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 105 Earth and Related Environmental Sciences > Environmental Sciences (social aspects to be 507)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
Keywords:cytochrome P450, metabolite formation, citalopram, sertraline, venlafaxine, metoprolol, environmental toxicology
URN:NBN:urn:nbn:se:slu:epsilon-p-107205
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-107205
Additional ID:
Type of IDID
DOI10.3390/molecules25112690
Web of Science (WoS)000553858800227
ID Code:17460
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:18 Sep 2020 08:19
Metadata Last Modified:18 Sep 2020 08:19

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