No major influence of chronic dietary flavonoid administration on CYP3A2 activity and expression in rats

Abstract

Dietary flavonoids such as chrysin and quercetin (from fruits) and daidzein and genistein (from soy) have the potential to modulate the activity and expression levels of phase I and II enzymes. This study was performed to investigate the influence of these flavonoids on ex vivo CYP3A2 activity and expression after chronic administration in rats. Male Sprague-Dawley rats were orally administered with various doses of the flavonoids (chrysin and quercetin – 5, 50 and 100 mg/kg/day, n = 6, daidzein and genistein - 25 mg/kg/day, n = 3) along with vehicle (0.5% carboxymethyl cellulose, CMC, n = 6) and untreated controls (n = 3) for 14 days. Liver microsomes prepared from these rats were screened for CYP3A2 activity (midazolam 1′-hydroxylation) and protein levels using western blot analysis. There were no significant differences in the formation of 1′-hydroxy midazolam between the various treatments: chrysin (5, 50, and 100 mg/kg/day – 23.4 ± 9.5, 23.8 ± 11.0, 19.6 ± 3.8 pmoles/mg/min), quercetin (5, 50, and 100 mg/kg/day – 27.8 ± 7.5, 24.9 ± 9.3, 25 ± 9.3 pmoles/mg/min), diadzein (21.9 ± 1.4 pmoles/mg/min), genistein (17 ± 2.6 pmoles/mg/min) versus CMC (24.1 ± 2.6 pmoles/mg/min) and untreated control (24.5 ± 6.1 pmoles/mg/min). No major differences were observed in CYP3A2 expression between the various treatments. These results indicate that chronic administration of chrysin, quercetin, diadzein and genistein may not influence CYP3A2 activity and expression. Supported by NCI Grant CA102405 (PI: L.V. Iyer).