Abstract
1. Sixteen naturally occurring flavonoids were investigated as substrates for cytochrome P450 in uninduced and Aroclor 1254-induced rat liver microsomes. Naringenin, hesperetin, chrysin, apigenin, tangeretin, kaempferol, galangin and tamarixetin were all metabolized extensively by induced rat liver microsomes but only to a minor extent by uninduced microsomes. No metabolites were detected from eriodictyol, taxifolin, luteolin, quercetin, myricetin, fisetin, morin or isorhamnetin. 2. The identity of the metabolites was elucidated using lc-ms and H-1-nmr, and was consistent with a general metabolic pathway leading to the corresponding 3',4'-dihydroxylated flavonoids either by hydroxylation or demethylation. Structural requirements for microsomal hydroxylation appeared to be a single or no hydroxy group on the B-ring of the flavan nucleus. The presence of two or more hydroxy groups on the B-ring seemed to prevent further hydroxylation. The results indicate that demethylation only occurs in the B-ring when the methoxy group is positioned at C-4'-, and not at the C-3'-position. 3. The CYP1A isozymes were found to be the main enzymes involved in flavonoid hydroxylation, whereas other cytochrome P450 isozymes seem to be involved in flavonoid demethylation.
| Originalsprog | Udefineret/Ukendt |
|---|---|
| Tidsskrift | Xenobiotica |
| Vol/bind | 28 |
| Udgave nummer | 4 |
| Sider (fra-til) | 389-401 |
| Antal sider | 13 |
| ISSN | 0049-8254 |
| DOI | |
| Status | Udgivet - 1998 |
Emneord
- monooxygenase activities mutagenic activity in-vivo metabolism cytochrome-p-450 bioflavonoids quercetin constituents activation inhibition