Establishment and use of new MDCK II cells overexpressing both UGT1A1 and MRP2 to characterize flavonoid metabolism via the glucuronidation pathway.

ABSTRACT:

Scope

The purpose of this study is to characterize how overexpression of an efflux transporter and an UDP-glucuronosyltransferase (UGT) affects the cellular kinetics of glucuronidation processes.

Methods and results

A new MDCK II cell line overexpressing both MRP2 and UGT1A1 (MDCKII-UGT1A1/MRP2 cells) was developed and used to determine how overexpression of an efflux transporter affects the kinetics of cellular flavonoid glucuronide production. The results showed that most model flavonoids (from a total of 13) were mainly metabolized into glucuronides in the MDCKII-UGT1A1/MRP2 cells and the glucuronides were rapidly excreted. Flavonoids with three or fewer hydroxyl group at 7, 3' or 6 hydroxyl group were also metabolized into sulfates. Mechanistic studies using 7-hydroxylfl

SUBMITTER: Wang M 

PROVIDER: S-EPMC5358013 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature