The impact of selected silybins on the efflux of ivermectin by P-glycoprotein from Haemonchus contortus

Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Denisa Husárová Supervisor: doc. Ing. Petra Matoušková, PhD. Title of Diploma Thesis: The impact of selected silybins on the efflux of ivermectin by P- glycoprotein from Haemonchus contortus P-glycoprotein (P-gp) is an ATP-driven transmembrane transporter. It can efflux a broad variety of structurally diverse and functionally unrelated hydrophobic compounds. Over- expression of P-gp is often associated with multidrug resistance. This has been a major obstacle in stopping effective therapy for parasitic diseases.1 P-gp is probably responsible for the drug resistance of ivermectin, a drug used in human and veterinary medicine to treat parasitic diseases caused by Nematoda. This study aims to use silybins, which can potentially cause an inhibition of P-gp, in other words, could promote an intracellular effect of ivermectin. During this study, we have been using 2 types of cells, with (transfected) and without the expression of P-gp. Both types of cells were foremostly used for verification of IC50 of ivermectin and doxorubicin. In the next step, the effects of individual silybin extracts on the cell line were evaluated as part of the preparation for the final plan, which in the future would involve...