Effects of flavonoids on cytochrome P‐450 from rat liver microsomes: Inhibition of enzyme activities and protection against peroxidative damage

A series of flavonoids, able to inhibit non‐enzymic and enzymic lipid peroxidation, were investigated as inhibitors of cytochrome P‐450 mediated reactions (aminopyrine N‐demethylation and aniline hydroxylation) in rat liver microsomes. The most potent compounds were chrysin, luteolin, amentoflavone and eriodictyol (aminopyrine N‐demethylation) and apigenin, kaempferol and quercetin (aniline hydroxylation). Some structure‐activity relationships were established for inhibition of aminopyrine N‐demethylation and it was observed that the resorcinol configuration of the ring A is a determinant feature, whereas O‐glycosylation abolished the activity. Most of the compounds showed lower activity on aniline hydroxylation. The presence of these flavonoids during incubation of microsomes in a medium containing NADPH did not modify the cytochrome P‐450 concentration and protected against lipid peroxidation induced degradation of this cytochrome.