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

In vitro and in vivo activation of oxidative drug metabolism by flavonoids.

Several naturally occurring and synthetic flavonoids were studied for their effects on the metabolism of zoxazolamine to 6-hydroxyzoxazolamine. Flavone, nobiletin, tangeretin and 7,8-benzoflavone (50-250 microM) stimulated the metabolism of zoxazolamine by liver microsomes obtained from 5-day-old rats. Evidence was obtained indicating that flavone changed the apparent Km and Vmax values for zoxazolamine hydroxylation. The i.p. administration of 5 mumol of flavone, nobiletin, tangeretin or 7,8-benzoflavone concurrently with 740 nmol of zoxazolamine immediately stimulated the total body metabolism of zoxazolamine to 6-hydroxyzoxazolamine. The magnitude of the flavone-mediated increases in zoxazolamine hydroxylation in vivo was dependent on the dose of flavone and the dose of zoxazolamine administered. The i.p. administration of 5 mumol of flavone caused a 3- to 5-fold stimulation in the in vivo metabolism of 740 to 3000 nmol of zoxazolamine, but flavone had little or no stimulatory effect when 74 nmol of zoxazolamine were administered. Flavone stimulated zoxazolamine metabolism both in vitro and in vivo when control or phenobarbital-treated rats were used, but flavone inhibited the in vitro and in vivo hydroxylation of zoxazolamine when rats induced with 5,6-benzoflavone were studied. Although flavone activated zoxazolamine metabolism in vivo in neonatal rats, flavone did not activate the in vivo metabolism of benzo(a)pyrene. The in vitro addition of the hydroxylated flavonoids apigenin, chrysin, fisetin, morin and quercetin inhibited the hydroxylation of zoxazolamine by liver microsomes from neonatal rats, but studies with quercetin and apigenin indicated that these flavonoids had no effect on the in vivo metabolism of zoxazolamine.[1]

References

  1. In vitro and in vivo activation of oxidative drug metabolism by flavonoids. Lasker, J.M., Huang, M.T., Conney, A.H. J. Pharmacol. Exp. Ther. (1984) [Pubmed]
 
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