RT Journal Article
SR Electronic
T1 In vivo and in vitro glucuronidation of the flavonoid diosmetin in rats.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1157
OP 1166
VO 21
IS 6
A1 J A Boutin
A1 F Meunier
A1 P H Lambert
A1 P Hennig
A1 D Bertin
A1 B Serkiz
A1 J P Volland
YR 1993
UL http://dmd.aspetjournals.org/content/21/6/1157.abstract
AB Flavonoids form an important family of compounds widely present in plants and therefore in food, sometimes as substitutes for synthetic antioxidants. Although the excretion routes of flavonoids in animals has been explored, little is known about the details of their conjugation in the xenobiotic metabolism pathway. In this study, we investigate the metabolism of diosmetin as a model compound in the rat, particularly its level in blood after treatment (100 mg/kg, po) and the presence of its glucuronide(s) in both blood and urine. We demonstrate that after po treatment of the rat, a rapid glucuronidation takes place and that diosmetin circulates as glucuronides, whereas no free diosmetin is present in blood and urine. The glucuronides formed are present in the blood plasma at a high level (approximately 10 micrograms/ml), for at least 6 hr after the treatment and the conjugates are excreted in urine. We have detected four different glucuronides in blood and characterized the two major ones after purification by a combination of MS, NMR, and UV spectroscopy: diosmetin-7,3'-diglucuronide and diosmetin-3'-glucuronide. A brief characterization of the in vitro glucuronidation of some flavonoid compounds using liver microsomal preparations suggests that this important class of natural compounds might be conjugated by a specific isoform of UDP-glucuronosyltransferase. Thus, this work brings evidence that diosmetin is rapidly glucuronoconjugated in the rat and provides an explanation for the low po bioavailability of the unchanged compound that can be generalized to this important class of natural compounds.