Gene Expression Profiling of 1alpha,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F22%3A10444098" target="_blank" >RIV/00216208:11160/22:10444098 - isvavai.cz</a>
Alternative codes found
RIV/75010330:_____/22:00013849 RIV/00216208:11140/22:10444098
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=V0nDexLzhj" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=V0nDexLzhj</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/mnfr.202200070" target="_blank" >10.1002/mnfr.202200070</a>
Alternative languages
Result language
angličtina
Original language name
Gene Expression Profiling of 1alpha,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes
Original language description
Scope: CYP3A4 is the most important drug-metabolizing enzyme regulated via the vitamin D receptor (VDR) in the intestine. However, less is known about VDR in the regulation of CYP3A4 and other drug-metabolizing enzymes in the liver. Methods and Results: This study investigates whether 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) regulates major cytochrome P450 enzymes, selected phase I and II enzymes, and transporters involved in xenobiotic and steroidal endobiotic metabolism in 2D and 3D cultures of human hepatocytes. The authors found that 1alpha,25(OH)2D3 increases hepatic CYP3A4 expression and midazolam 1'-hydroxylation activity in 2D hepatocytes. The results are confirmed in 3D spheroids, where 1alpha,25(OH)2D3 has comparable effect on CYP3A4 mRNA expression as 1alpha-hydroxyvitamin D3, an active vitamin D metabolite. Other regulated genes such as CYP1A2, AKR1C4, SLC10A1, and SLCO4A1 display only mild changes in mRNA levels after 1alpha,25(OH)2D3 treatment in 2D hepatocytes. Expression of other cytochrome P450, phase I and phase II enzyme, or transporter genes are not significantly influenced by 1alpha,25(OH)2D3. Additionally, the effect of VDR activation on CYP3A4 mRNA expression is abolished by natural dietary compound sulforaphane, a common suppressor of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Conclusion: This study proposes that VDR or vitamin D supplementation is unlikely to significantly influence liver detoxification enzymes apart from CYP3A4.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
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
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Nutrition and Food Research
ISSN
1613-4125
e-ISSN
1613-4133
Volume of the periodical
66
Issue of the periodical within the volume
9
Country of publishing house
DE - GERMANY
Number of pages
17
Pages from-to
2200070
UT code for WoS article
000762216200001
EID of the result in the Scopus database
2-s2.0-85125352623