Gene Expression Profiling of 1????,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73612949" target="_blank" >RIV/61989592:15310/22:73612949 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202200070" target="_blank" >https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202200070</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/mnfr.202200070" target="_blank" >10.1002/mnfr.202200070</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Gene Expression Profiling of 1????,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes

Popis výsledku v původním jazyce

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 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) 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 1 alpha,25(OH)(2)D-3 increases hepatic CYP3A4 expression and midazolam 1 &apos;-hydroxylation activity in 2D hepatocytes. The results are confirmed in 3D spheroids, where 1 alpha,25(OH)(2)D-3 has comparable effect on CYP3A4 mRNA expression as 1 alpha-hydroxyvitamin D-3, an active vitamin D metabolite. Other regulated genes such as CYP1A2, AKR1C4, SLC10A1, and SLCO4A1 display only mild changes in mRNA levels after 1 alpha,25(OH)(2)D-3 treatment in 2D hepatocytes. Expression of other cytochrome P450, phase I and phase II enzyme, or transporter genes are not significantly influenced by 1 alpha,25(OH)(2)D-3. 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.

Název v anglickém jazyce

Gene Expression Profiling of 1????,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic-Metabolizing Genes

Popis výsledku anglicky

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 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) 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 1 alpha,25(OH)(2)D-3 increases hepatic CYP3A4 expression and midazolam 1 &apos;-hydroxylation activity in 2D hepatocytes. The results are confirmed in 3D spheroids, where 1 alpha,25(OH)(2)D-3 has comparable effect on CYP3A4 mRNA expression as 1 alpha-hydroxyvitamin D-3, an active vitamin D metabolite. Other regulated genes such as CYP1A2, AKR1C4, SLC10A1, and SLCO4A1 display only mild changes in mRNA levels after 1 alpha,25(OH)(2)D-3 treatment in 2D hepatocytes. Expression of other cytochrome P450, phase I and phase II enzyme, or transporter genes are not significantly influenced by 1 alpha,25(OH)(2)D-3. 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10700 - Other natural sciences

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

MOLECULAR NUTRITION &amp; FOOD RESEARCH

ISSN

1613-4125

e-ISSN

1613-4133

Svazek periodika

66

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

17

Strana od-do

"2200070-1"-"2200070-17"

Kód UT WoS článku

000762216200001

EID výsledku v databázi Scopus

2-s2.0-85125352623