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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 
 

Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes.

Flavonoids are widely occurring in our diet. In this study, the effects of nine flavonoids on acetaminophen (APAP) oxidation and related cytochrome P450 (P450) enzyme activities were investigated. With rat liver microsomes, APAP oxidation was stimulated 2- to 4-fold by 50 microM flavone or tangeretin and inhibited 65% by myricetin or quercetin. Only a slight inhibition of APAP oxidation was caused by naringenin. All the effects cited herein were from experiments with 50 microM flavonoids. With human liver microsomal samples that had high P450 3A4 activity, APAP oxidation was stimulated 1.6- to 3.0-fold by tangeretin, nobiletin, and flavone, but inhibited 40-60% by myricetin and quercetin. With human P450 1A2 expressed in Hep G2 cells, APAP oxidation was inhibited completely by flavone or quercetin. With expressed P450 3A4, this reaction was stimulated 4-fold by flavone, but inhibited 60% by quercetin. The expressed human P450 2E1-dependent APAP oxidation was only slightly affected by flavone and quercetin. The mechanisms of the inhibition and stimulation were complex and varied with the different P450 forms and flavonoids used in the system. The O-deethylation of ethoxyresorufin in rat liver microsomes was effectively inhibited by myricetin (IC50, 15 microM) and moderately inhibited by flavone, tangeretin, and quercetin (IC50, 50-80 microM); with P450 1A2 in Hep G2 cell microsomes, the activity was markedly inhibited by flavone (IC50, 2.5 microM). The microsomal P450s 2E1 and 3A activities were inhibited by myricetin (IC50, 85-90 microM), but not effectively inhibited by other flavonoids.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

  1. Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Li, Y., Wang, E., Patten, C.J., Chen, L., Yang, C.S. Drug Metab. Dispos. (1994) [Pubmed]
 
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