Studium vybraných flavonoidů jako modulátorů cytochromu P450 3A4

Abstract

Flavonoidy jsou sekundární metabolity rostlin vykazující širokou škálu biologických aktivit. Velká pozornost jim je v nována hlavn pro jejich antioxida ní vlastnosti. Proto se v sou asné dob zvyšuje konzumace t chto p írodních látek p edevším ve form potravních dopl k . Navíc tyto slou eniny vykazují antivirové, protizán tlivé i hepatoprotektivní ú inky a n které z nich mají také mutagenní a/nebo prooxida ní vlastnosti. Mimo jiné jsou d ležité interakce flavonoid s biotransforma ními enzymy, nap . cytochromy P450, ímž mohou zasahovat do metabolismu lé iv nebo proces kancerogenese. V této bakalá ské práci byl studován vliv vybraných flavonoidních slou enin dihydromyricetinu a myricetinu na expresi a aktivitu cytochromu P450 3A4. Po premedikaci potkan t mito flavonoidy nebyla zjišt na indukce CYP3A4. Dihydromyricetin i myricetin však inhibují CYP3A4. Byla stanovena jejich koncentrace, p i které je dosaženo 50% maxima inhibi ního efektu, pro dihydromyricetin IC50 = 25 µM a pro myricetin IC50 = 24 µM. Klí ová slova: Imunodetekce, HPLC, inhibice, indukce

Flavonoids are secondary metabolites of plants exhibiting a wide range of biological activities. Special attention is paid to them mainly because of their antioxidant properties. Consumption of these natural substances is currently increasing especially in the form of dietary supplements. In addition, these compounds exhibit antiviral, anti-inflammatory or hepatoprotective effects and some of them also exhibit mutagenic and/or pro-oxidative properties. The study of flavonoid interactions with biotransformation enzymes such as cytochromes P450 are important because of their possible interference with the metabolism of drugs or carcinogenesis processes. In this bachelor thesis the influence of selected flavonoid compounds, dihydromyricetin and myricetin, on the expression and activity of cytochrome P450 3A4 was studied. The flavonoid premedication of rats did not resulted in induction of CYP3A4. However, dihydromyricetin and myricetin inhibit CYP3A4. IC50 were determined as 25 M for dihydromyricetin and 24 M for myricetin. Key words: Immunodetection, HPLC, inhibition, induction (In Czech)