C 031: INHIBITION OF CYTOCHROME P450 BY NATURAL PRODUCTS AS AN ANTIMUTAGENESIS MECHANISM

J Pharm Pharmacogn Res 2(Suppl. 1): S92, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 031: INHIBITION OF CYTOCHROME P450 BY NATURAL PRODUCTS AS AN ANTIMUTAGENESIS MECHANISM

Espinosa-Aguirre JJ.

Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), D.F., Mexico.
Abstract

CYP enzymes are involved in the metabolism of xenobiotics as well as some endogenous compounds. Its activities lead to the production of mutagenic and carcinogenic entities that can react with important macromolecules like proteins and nucleic acids. In theory, Inhibition of CYP catalysis could lead to inhibition of the mutagenic and carcinogenic processes considering the inhibitory compounds as beneficial chemoprotective agents. Using in vitro biochemical methods we have tested the CYP inhibitory capacity of several plant derived compounds like bergamotin, dehydrobergamotin and naringin from grapefruit, quercetin and chiro-inositol from Heteroteca inuloides, mangiferin from Mangifera indica and thalassiolin b from Thalassia testidinum. Results obtained showed the CYP inhibitory activity of these compounds, being bergamotin and thalassiolin b of the molecules with high inhibitory potential. Results from the Ames Assay in which we tested the antimutagenic properties of these compounds against known mutagens, shows that the inhibition of CYP activity can be traduced in an antimutagenic effect in this Assay. These effects were also confirmed in rat hepatic cells in culture, where effects on activity/expression of CYP1A1 were tested. The possible use of these antimutagenic substances as chemoprotective agents is discussed in the light of the existence of endogenous CYP substrates.