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.

摘要: 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 vitro-in silico approach. Methods results Concentration-response curves obtained from vitro PPARγ-reporter assays are converted to vivo dose-response physiologically based kinetic modeling-facilitated reverse dosimetry, which the benchmark dose levels resulting 50% effect above background level (BMD50 ) predicted subsequently compared exposure levels. Bixin activated PPARγ-mediated transcription concentration-dependent manner with similar potencies. Due differences kinetics, BMD50 values for PPARγ activation about 30-fold different, amounting 115 3505 mg kg bw-1 bixin, respectively. Human and/or supplemental estimated daily intakes may reach these but not pointing better possibilities by crocetin. Conclusion Based on approach, it plasma concentrations of likely that activate expression, without need human intervention study.