Effect of sesquiterpenes on biotransformation enzymes in tissue slices

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Tomáš Zárybnický Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Effect of sesquiterpenes on biotransformation enzymes in tissue slices Sesquiterpenes are secondary metabolites, produced mainly by higher plants. They are structurally diverse compounds with a large spectrum of biological activity. They possess antiphlogistic, antibacterial, antimalarial and antitumour activity. The aim of this diploma thesis was to find out how selected sesquiterpenes - α-humulene (HUM) and β-caryophyllene (BC) influence the activity of chosen biotransformation enzymes - NAD(P)H-chinon oxidoreductase 1 (NQO1), glutathione S-transferase (GST) and sulfotransferase (SULT). Precision-cut tissue slices from the rat liver (Rattus norvegicus, tribe Wistar) were chosen as model system. Thickness of the slices was approximately 200-250 µm and diameter 8 mm. Liver slices were preincubated for 30 minutes and then incubated for 24 hours (in presence of HUM and BC) in a 12-well plate in the atmosphere of pneumoxide (95% O2/5% CO2). Samples of liver slices and medium were taken upon replacing the medium after preincubation (time 0 hours) and then after 3, 6 and 24 hours. Both sesquiterpenes, HUM..