STUDY OF INFLUENCE OF ESTRADIOL ON THE ACTIVITY OF P-GLYCOPROTEIN IN VITRO

Background. P-Glycoprotein (Pgp) is a transport protein that provides protection of organs and tissues from xenobiotics being its substrates, through excretion of them from cells into the extracellular space and biological fluids. Aim. To study the effect of estradiol on Pgp activity in vitro on Caco-2 cell line. Materials and Methods. The studies were performed on Caco-2 cell line. Pgp activity was analyzed by the transport of its marker substrate, fexofenadine, in Transwell system. The concentration of fexofenadine was evaluated by HPLC. The amount of Pgp was determined by ELISA method. The experiment included the following series of cells: cells preincubated with clean transport medium without addition of any substances (control series); the effect of rifampicin at a concentration of 10 μM on Pgp activity and synthesis in preincubation for 3 days (induction control); the effect of estradiol at concentrations of 1 and 10 μM on Pgp activity and synthesis in preincubation for 30 min; the effect of estradiol at concentrations of 1 and 10 μM on Pgp activity and synthesis in preincubation for 3 days. Results. Estradiol at concentrations of 1 and 10 μM in incubation with cells for 30 min did not show any reliable influence on the activity and synthesis of Pgp, the same as 1 μM estrogen during incubation for 3 days. At the same time, estradiol at a concentration of 10 μM induced increase in the activity and synthesis of the transport protein in incubation for 3 days. Conclusion. In in vitro experiments on Caco-2 cells, estradiol at a concentration of 10 μM increases the activity and synthesis of P-glycoprotein transporter in incubation for 3 days.