In vitro inhibition of human CYP2E1 and CYP3A by quercetin and myricetin in hepatic microsomes is not gender dependent
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
28232125
DOI
10.1016/j.tox.2017.02.012
PII: S0300-483X(17)30058-6
Knihovny.cz E-zdroje
- Klíčová slova
- Cytochrome P450, Females, Flavonols, Hepatic microsomes, Males, isorhamnetin (PubChem CID: 5281654), myricetin (PubChem CID: 5281672), quercetin (PubChem CID: 5280343),
- MeSH
- cytochrom P-450 CYP2E1 metabolismus MeSH
- cytochrom P-450 CYP3A metabolismus MeSH
- flavonoidy farmakologie MeSH
- hydroxylace MeSH
- inhibitory cytochromu P450 CYP2E1 farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- jaterní mikrozomy účinky léků metabolismus MeSH
- kumariny metabolismus MeSH
- lidé MeSH
- nitrofenoly metabolismus MeSH
- quercetin analogy a deriváty farmakologie MeSH
- sexuální faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 3-methylquercetin MeSH Prohlížeč
- 4-nitrophenol MeSH Prohlížeč
- 7-benzyloxy-4-trifluoromethylcoumarin MeSH Prohlížeč
- cytochrom P-450 CYP2E1 MeSH
- cytochrom P-450 CYP3A MeSH
- flavonoidy MeSH
- inhibitory cytochromu P450 CYP2E1 MeSH
- inhibitory enzymů MeSH
- kumariny MeSH
- myricetin MeSH Prohlížeč
- nitrofenoly MeSH
- quercetin MeSH
This is the first in vitro study to investigate gender-related differences in the regulation of human cytochrome P450 by the flavonoids. Activities of CYP2E1 and CYP3A were measured in the presence of quercetin, myricetin, or isorhamnetin in hepatic microsomal pools from male and female donors. Hydroxylation of p-nitrophenol (PNPH) was measured to determine CYP2E1 activity, and O-dealkylation of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) was measured to determine CYP3A activity. Quercetin, but not myricetin or isorhamnetin, competitively inhibited PNPH activity in human recombinant cDNA-expressed CYP2E1 with the Ki=52.1±6.31μM. In the human microsomes, slight inhibition of PNPH activity by quercetin was not considered as physiologically relevant. Quercetin inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 competitively with the Ki=15.4±1.52μM, and myricetin - noncompetitively with the Ki=74.6±7.99μM. The degree of inhibition by quercetin was similar between genders. Myricetin showed somewhat stronger inhibition in female pools, but the Ki values were higher than physiologically relevant concentrations. Isorhamnetin did not affect either PNPH or BFC activity. We concluded that observed inhibition of CYP2E1 and CYP3A by some flavonols were not gender-dependent.
Citace poskytuje Crossref.org
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