Evidence for tangeretin O-demethylation by rat and human liver microsomes

1. Tangeretin, a polymethoxylated flavone, was studied as a substrate for cytochrome P450-catalysed demethylation reactions by rat and human liver microsomes. Evidence has been presented for the production of formaldehyde in the presence of tangeretin and NAD(P)H. Kinetic studies showed a Km value f...

Full description

Bibliographic Details
Published in:Xenobiotica
Main Authors: Canivenc Lavier, Marie-Chantal, Brunold, C., Siess, Marie-Hélène, Suschetet, Marc
Other Authors: UR 0938 Unité de Toxicologie nutritionnelle, Institut National de la Recherche Agronomique (INRA), UR 0938 DIJ TOX NUTRITIONN Unité de Toxicologie nutritionnelle
Format: Article in Journal/Newspaper
Language:English
Published: HAL CCSD 1993
Subjects:
Rat
Pharmacologie
Biologie animale
human
liver function tests
enzymic activity
2-phenyl-2-ene-benzopyran-4-one compounds
rattus rattus
homme
tangeritine
foie
métabolisme
déméthylation
activité enzymatique
inhibition
flavone
cytochrome p450
microsome
[SDV]Life Sciences [q-bio]
Rattus rattus
Online Access:https://hal.archives-ouvertes.fr/hal-01856403
https://doi.org/10.3109/00498259309059379
Description
Summary:1. Tangeretin, a polymethoxylated flavone, was studied as a substrate for cytochrome P450-catalysed demethylation reactions by rat and human liver microsomes. Evidence has been presented for the production of formaldehyde in the presence of tangeretin and NAD(P)H. Kinetic studies showed a Km value for tangeretin of about 18 μM in both species. 2. The reaction was inhibited by CO, piperonyl butoxide, 7,8-benzoflavone, propyl gallate, aminobenzothiazole and metyrapone. 3. Rats pretreated with classical cytochrome P450 inducers (Aroclor 1254, 3-methylcholanthrene, phenobarbital, dexamethasone and ciprofibrate) or with flavonoids (flavone, flavanone, quercetin and tangeretin) resulted in increased microsomal demethylation of tangeretin after 3-methylcholanthrene and flavone only. Tangeretin did not enhance its own metabolism. 4. Tangeretin interacted with the oxidized form of cytochrome P450 to produce a reverse type I spectrum. 5. Results indicate that tangeretin is metabolized in liver microsomes by an O-demethylation reaction involving cytochrome P450.

Similar Items