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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12520%2F18%3A43897177" target="_blank" >RIV/60076658:12520/18:43897177 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0045653518307288" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045653518307288</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.chemosphere.2018.04.080" target="_blank" >10.1016/j.chemosphere.2018.04.080</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemosphere

ISSN

0045-6535

e-ISSN

—

Svazek periodika

205

Číslo periodika v rámci svazku

08/2018

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

380-386

Kód UT WoS článku

000439640900043

EID výsledku v databázi Scopus

2-s2.0-85047395336