Hepatic biotransformation of non-psychotropic phytocannabinoids and activity screening on cytochromes P450 and UDP-glucuronosyltransferases
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985858%3A_____%2F23%3A00575446" target="_blank" >RIV/67985858:_____/23:00575446 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/23:73621007 RIV/61989592:15310/23:73621007
Result on the web
<a href="https://hdl.handle.net/11104/0345231" target="_blank" >https://hdl.handle.net/11104/0345231</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.taap.2023.116654" target="_blank" >10.1016/j.taap.2023.116654</a>
Alternative languages
Result language
angličtina
Original language name
Hepatic biotransformation of non-psychotropic phytocannabinoids and activity screening on cytochromes P450 and UDP-glucuronosyltransferases
Original language description
This study examined the biotransformation of phytocannabinoids in human hepatocytes. The susceptibility of the tested compounds to transformations in hepatocytes exhibited the following hierarchy: cannabinol (CBN) > cannabigerol (CBG) > cannabichromene (CBC) > cannabidiol (CBD). Biotransformation included hydroxylation, oxidation to a carboxylic acid, dehydrogenation, hydrogenation, dehydration, loss/shortening of alkyl, glucuronidation and sulfation. CBN was primarily metabolized by oxidation of a methyl to a carboxylic acid group, while CBD, CBG and CBC were preferentially metabolized by direct glucuronidation. The study also screened for the activity of recombinant human cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs), which could catalyze the hydroxylation and glucuronidation of the tested compounds, respectively. We found that CBD was hydroxylated mainly by CYPs 2C8, 2C19, 2D6, CBN by 1A2, 2C9, 2C19 and 2D6, and CBG by 2B6, 2C9, 2C19 and 2D6. CBC exhibited higher susceptibility to CYP-mediated transformation than the other tested compounds, mainly with CYPs 1A2, 2B6, 2C8, 2C19, 2D6 and 3A4 being involved. Further, CBD was primarily glucuronidated by UGTs 1A3, 1A7, 1A8, 1A9 and 2B7, CBN by 1A7, 1A8, 1A9 and 2B7, CBG by 1A3, 1A7, 1A8, 1A9, 2B4, 2B7 and 2B17, and the glucuronidation of CBC was catalyzed by UGTs 1A1, 1A8, 1A9 and 2B7.
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
30108 - Toxicology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Toxicology and Applied Pharmacology
ISSN
0041-008X
e-ISSN
1096-0333
Volume of the periodical
476
Issue of the periodical within the volume
1 OCT
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
116654
UT code for WoS article
001071474000001
EID of the result in the Scopus database
2-s2.0-85168853289