Verification of flavonoids effect on bovine cytochrome P450 activity in liver S9 fraction

Flavonoids are very promising feed additives in dairy cows undergoing oxidative stress during the peripartum period and could potentially be used to prevent or minimalize the course of fatty liver syndrome. However, there is no data of their effect on hepatic metabolism in cows. Thus, the aim of the study was to verify the effect of some dietary flavonoids on the activity of cytochrome P450 (CYP450) in bovine liver S9 fractions.

The experiments were conducted on hepatic S9 fractions from routinely slaughtered adult cows. The effect of apigenin, quercetin and luteolin on 7-ethoxycoumarin O-deethylase (ECOD) activity, measured as the amount of created 7-hydroxycoumarin (7-OH), was used to monitor CYP450 activity.

The production of 7-OH in the absence of flavonoids amounted to 413.2 ± 83.8 pmol/mg of protein/min. All three flavonoids used in the concentration range of 1 – 100µM induced significant decrease of ECOD activity. The strongest inhibition of ECOD was observed when flavonoids were used in the highest dose, i.e. 100µM. The amount of produced 7-OH amounted then to 34.1 ± 5.5, 49.8 ± 3.3 and 51.7 ± 3.9% of 7-OH produced in the absence of flavonoids, for apigenin, quercetin and luteolin, respectively. If used in the lowest dose (1µM) apigenin inhibited ECOD activity significantly weaker (87.5 ± 2.7% of the control reaction) than quercetin and luteolin (65.3 ± 4.7 and 60.9 ± 4.5%).

In conclusion, apigenin, quercetin and luteolin proved to be potent inhibitors of ECOD and thereby CYP450 activity. However, the observed effect was neither dose-dependent nor variable between flavonoids.

The study was supported by a research grant from the National Science Centre Poland No. UMO- 2012/05/D/NZ9/01610.