Bergamottin is a competitive inhibitor of CYP1A1 and is antimutagenic in the Ames test

Grapefruit juice (GJ) is a well known Cytochrome P450 (CYP) inhibitor; CYP3A is one of the most affected subfamily leading to anticarcinogenic and antimutagenic effects when GJ is administered to experimental Animals in combination with mutagenic/carcinogenic agents metabolized by CYP3A. Bergamottin, naringin and dihydroxybergamottin are three main constituents contained within GJ and their inhibitory effect against CYP3A4 has been well documented. Reports suggest that CYP3A is not the only one affected but CYP1A and 2B are also affected by GJ. To explore this last possibility in depth we tested the in vitro capacity of bergamottin, naringin and dihydroxybergamottin to inhibit the activity of CYP1A and 2B subfamilies and found that bergamottin showed the strongest inhibitory effect and naringin showed no inhibition at all. Therefore, we decided to biochemically characterize the inhibitory properties of bergamottin. CYP1A1 Supersome® used in this study showed a Km(app)=0.0723 μM and a Vm(app)=6.141 μU/pmol with substrate ethoxyresorufin, and the biochemical characterization of bergamottin CYP1A1 inhibitory effect revealed that it is a competitive inhibitor with a Ki=10.703 nM. We also confirmed the antimutagenicity of this compound against the mutagenic effect of 3-methylcholanthrene and benzo[a]pyrene in the Ames test.