Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F18%3A00100907" target="_blank" >RIV/00216224:14110/18:00100907 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/18:10383217 RIV/61989592:15110/18:73587096

Výsledek na webu

<a href="http://dx.doi.org/10.1124/dmd.117.079582" target="_blank" >http://dx.doi.org/10.1124/dmd.117.079582</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1124/dmd.117.079582" target="_blank" >10.1124/dmd.117.079582</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models

Popis výsledku v původním jazyce

The endocannabinoid system is important for many physiological and pathological processes, but its role in the regulation of liver cytochromes P450 (CYPs) is still unknown.We studied the influence of the endocannabinoid oleamide on rat and human liver CYPs. Oleamide was administered i.p. to rats at doses of 0.1, 1 and 10 mg/kg/day for 7 days. The content and activity of key CYPs was evaluated in rat liver microsomes. Moreover, its interactions with nuclear receptors regulating CYP genes and serum levels of their ligands (prolactin, corticosterone, and free triiodothyronine) were tested in vitro CYP inhibition assays. Decreased protein levels and metabolic activities of CYP1A2, CYP2B, and CYP2C11 along with a drop in metabolic activity of CYP2D2 were observed in animals treated with oleamide (10 mg/kg/day). The activities of CYP2C6, CYP2A, and CYP3A and the levels of hormones were not altered. In vitro, oleamide exhibited a weak inhibition of rat CYP1A2, CYP2D2, and CYP2C6. The activities of rat CYP2A, CYP2B, CYP2C11, and CYP3A and human CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were not altered. Oleamide did not interact with human pregnane X, constitutive androstane and aryl hydrocarbon receptors in reporter gene experiments and did not regulate their target CYP genes in primary human hepatocytes. Our results indicate that oleamide caused the downregulation of some rat liver CYPs, and hormones are not mediators of this effect. In vitro oleamide inhibits mainly rat CYP2C6 and it is neither an agonist nor antagonist of major human nuclear receptors involved in the regulation of xenobiotic metabolism.

Název v anglickém jazyce

Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models

Popis výsledku anglicky

The endocannabinoid system is important for many physiological and pathological processes, but its role in the regulation of liver cytochromes P450 (CYPs) is still unknown.We studied the influence of the endocannabinoid oleamide on rat and human liver CYPs. Oleamide was administered i.p. to rats at doses of 0.1, 1 and 10 mg/kg/day for 7 days. The content and activity of key CYPs was evaluated in rat liver microsomes. Moreover, its interactions with nuclear receptors regulating CYP genes and serum levels of their ligands (prolactin, corticosterone, and free triiodothyronine) were tested in vitro CYP inhibition assays. Decreased protein levels and metabolic activities of CYP1A2, CYP2B, and CYP2C11 along with a drop in metabolic activity of CYP2D2 were observed in animals treated with oleamide (10 mg/kg/day). The activities of CYP2C6, CYP2A, and CYP3A and the levels of hormones were not altered. In vitro, oleamide exhibited a weak inhibition of rat CYP1A2, CYP2D2, and CYP2C6. The activities of rat CYP2A, CYP2B, CYP2C11, and CYP3A and human CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were not altered. Oleamide did not interact with human pregnane X, constitutive androstane and aryl hydrocarbon receptors in reporter gene experiments and did not regulate their target CYP genes in primary human hepatocytes. Our results indicate that oleamide caused the downregulation of some rat liver CYPs, and hormones are not mediators of this effect. In vitro oleamide inhibits mainly rat CYP2C6 and it is neither an agonist nor antagonist of major human nuclear receptors involved in the regulation of xenobiotic metabolism.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

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

Drug Metabolism and Disposition

ISSN

0090-9556

e-ISSN

1521-009X

Svazek periodika

46

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

913-923

Kód UT WoS článku

000439228300016

EID výsledku v databázi Scopus

2-s2.0-85049344460