Evaluation of 3,3',4'-trihydroxyflavone and 3,6,4'-trihydroxyflavone (4'-O-glucuronidation) as the in vitro functional markers for hepatic UGT1A1.

ABSTRACT: Identifying uridine 5'-diphospho-(UDP)-glucuronosyltransferase (UGT)-selective probes (substrates that are primarily glucuronidated by a single isoform) is complicated by the enzymes' large overlapping substrate specificity. Here, regioselective glucuronidation of two flavonoids, 3,3',4'-trihydroxyflavone (3,3',4'-THF) and 3,6,4'-trihydroxyflavone (3,6,4'-THF), is used to probe the activity of hepatic UGT1A1. The glucuronidation kinetics of 3,3',4'-THF and 3,6,4'-THF was determined using 12 recombinant human UGT isoforms and pooled human liver microsomes (pHLM). The individual contribution of main UGT isoforms to the metabolism of the two flavonoids in pHLM was estimated using the relative activity factor approach. UGT1A1 activity correlation analyses using flavonoids-4'-O-glucuronidation

SUBMITTER: Wu B 

PROVIDER: S-EPMC3404744 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature