Combining In Vitro Data and Physiologically Based Kinetic Modeling Facilitates Reverse Dosimetry to Define In Vivo Dose-Response Curves for Bixin- and Crocetin-Induced Activation of PPARγ in Humans.

ABSTRACT:

Scope

It is investigated whether at realistic dietary intake bixin and crocetin could induce peroxisome proliferator-activated receptor γ (PPARγ)-mediated gene expression in humans using a combined in vitro-in silico approach.

Methods and results

Concentration-response curves obtained from in vitro PPARγ-reporter gene assays are converted to in vivo dose-response curves using physiologically based kinetic modeling-facilitated reverse dosimetry, from which the benchmark dose levels resulting in a 50% effect above background level (BMD₅₀ ) are predicted and subsequently compared to dietary exposure levels. Bixin and crocetin activated PPARγ-mediated gene transcription in a concentration-dependent manner with similar potencies. Due to differences in kinetics, the pre

SUBMITTER: Suparmi S 

PROVIDER: S-EPMC7003908 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature