Tetrabrominated bisphenol A inhibition studies on six cytochrome P450 enzymes in human liver microsomes

In this study, a system was designed, utilizing human microsomes, to determine if a flame retardant, tetrabromobisphenol A (TBBPA), inhibits cytochrome P450 (CYP) enzyme function. The six CYP reaction assays in this paper were used to measure if TBBPA causes a decreased rate of reaction for human liver CYP enzymes. In particular the six human liver CYP enzymes investigated were CYP 1A2, CYP 2D6, CYP 2C9, CYP 2C19, CYP 3A4 and CYP 3A5. TBBPA, at varying concentrations, was coincubated with specific substrates for each CYP isoform. Comparisons of the amount of metabolite formed revealed that TBBPA inhibited CYP 2C9 and CYP 3A4 enzyme activity, with IC50 values of 0.7 μM and 3.5 μM, respectively.