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

Viktoriia Burkina,Pham Thai Giang,Sidika Sakalli,Kateřina Grabicová,Andrea Vojs Staňová,Galia Zamaratskaia,Vladimir Zlabek

doi:10.3390/molecules25112690

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 Vmax = 1781 pmol/min/mg and Km = 29.7 μM. 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.

Highlights

The contamination of aquatic systems by human pharmaceuticals and personal care products is increasingly concerning
Common carp S9 fraction was initially characterized on activity of phase I enzymes, by using of known substrates, for CYP1A1 and CYP3A-like activity (Table 1)
Fish living in that pond

Summary

Introduction

The contamination of aquatic systems by human pharmaceuticals and personal care products is increasingly concerning. Once pharmaceuticals have been absorbed by the host organism and excreted as the parent compound, their metabolites, or both, can be transferred into wastewater treatment plant (WWTP) facilities. Such facilities do not have additional steps to remove pharmaceutically active compounds. WWTPs are recognized as hot spots for releasing pharmaceuticals into aquatic environments [1,2]. These compounds are considered as pseudo-persistent compounds in WWTP effluents due to regular prescription and continuous use.

Objectives

Methods

Results

Conclusion