Efeito de sucos de frutas amazônicas na atividade in vitro da glicoproteína-P e do citocromo P450 humanos

Abstract

The metabolism and the intracellular transport through cell membranes are among the main procedures governing the kinetics of drugs in physiological compartments. The enzyme CYP3A4, which belongs to the cytochrome P450 enzymatic complex, is responsible for the metabolism of the majority of drugs currently used and is crucial in many drug-drug interactions. In addition to it, the transporter P-glycoprotein membrane, ABC Family, is another factor responsible for interference in the kinetics of drugs. The interaction of these proteins with juices of some fruits from other countries, for example grapefruit, may affect the pharmacokinetics of many drugs. However, to the best of our knowledge, no investigation has been made evolving fruits from the Amazon region. For this study, first, we determined the phytochemical constituents such as total polyphenols and flavonoids juices of Amazon fruits açaí, buriti, camu-camu, cubiu, cupuaçu, jenipapo and taperebá. Has been reported, too, the effect of these juices on activity of P-gP and CYP3A4 which employs human recombinant protein and the cell line MES-SA/DX and liver microsomes. The acai juice showed the highest content of total polyphenols (102.56 ± 7.2 μg EAG/mL) and flavonoids (7.16 ± 0.58 μg EQ/mL). Regarding the inhibitory capacity of recombinant P-gP, cupuaçu juice had the highest rate. CYP3A4 was strongly inhibited by acai juice, buriti, camu-camu, cubiu and tapereba, with residual activity of 0%, while the positive control carambola juice had residual activity of 20%. According, the concentrations tested, the juices of Amazon fruits had the ability to interact mainly with CYP3A4 in vitro. However, further studies should be done to confirm these findings and to clarify the mechanisms involved in this phenomenon.