Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11160/18:10383217 RIV/61989592:15110/18:73587096
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Drug Metabolism and Disposition
ISSN
0090-9556
e-ISSN
1521-009X
Volume of the periodical
46
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
913-923
UT code for WoS article
000439228300016
EID of the result in the Scopus database
2-s2.0-85049344460