2018
Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models
DOVRTĚLOVÁ, Gabriela, Ondřej ZENDULKA, Kristýna NOSKOVÁ, Jan JUŘICA, Ondřej PEŠ et. al.Základní údaje
Originální název
Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models
Autoři
DOVRTĚLOVÁ, Gabriela (203 Česká republika, domácí), Ondřej ZENDULKA (203 Česká republika, garant, domácí), Kristýna NOSKOVÁ (203 Česká republika, domácí), Jan JUŘICA (203 Česká republika, domácí), Ondřej PEŠ (203 Česká republika, domácí), Jan DUŠEK (203 Česká republika), Alejandro CARAZO (724 Španělsko), Iveta ZAPLETALOVÁ (203 Česká republika), Nataša HLAVÁČOVÁ (703 Slovensko) a Petr PÁVEK (203 Česká republika)
Vydání
Drug Metabolism and Disposition, Bethesda, AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 2018, 0090-9556
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30104 Pharmacology and pharmacy
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 3.354
Kód RIV
RIV/00216224:14110/18:00100907
Organizační jednotka
Lékařská fakulta
UT WoS
000439228300016
Klíčová slova anglicky
cytochrome P450; enzyme inhibitors; liver; hepatic; pharmacokinetics
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 27. 1. 2021 13:04, Mgr. Tereza Miškechová
Anotace
V originále
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.
Návaznosti
| GA16-06106S, projekt VaV |
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| LM2015090, projekt VaV |
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| MUNI/A/0910/2017, interní kód MU |
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| MUNI/A/1132/2017, interní kód MU |
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