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Studium interakcí doplňků stravy s enzymy biotransformace xenobiotik
Bebová, Michaela ; Hodek, Petr (advisor) ; Hansíková, Hana (referee)
Currently, an increasing attention is being paid to phytochemicals as one of the most widely used chemopreventive compounds, generally considered as health-promoting and safe. Flavonoids representing a large group of phytochemicals are present in many dietary supplements formulated from natural sources. The consumption of these concentrated phytochemicals has dramatically increased in the recent decade. It appears, however, that the ingestion of flavonoids might be associated with some adverse effects. Some flavonoids are known modulators of enzymes involved in phase I and phase II metabolism of xenobiotics biotransformation, thus their induction may result in an increase of carcinogen activation. In this study, the effects of selected flavonoid compounds -naphthoflavone, - naphthoflavone, myricetin, and dihydromyricetin, and carcinogens (BaP, PhIP) on phase II metabolism enzymes, sulfotransferases (SULT), have been investigated. To determine the induction of SULT, antibodies for their immunodetection have been developed. Peptide antigens derived from sequences of selected rat sulfotransferases rSULT1A1, 1B1, 1C1, 1C2, 1C1/2, 1E1, and 2A1, were used as KLH conjugates for hen immunization to obtain yolk anti-peptide antibody (IgY). Fractions of IgY were isolated from eggs yolks by simple...
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Food Supplements as Activation Modulators of Food Carcinogens, Phase II Metabolism
Bebová, Michaela ; Hodek, Petr (advisor) ; Koblihová, Jitka (referee)
Heterocyclic aromatic amines (HAA) are representatives of carcinogenic and mutagenic compounds formed when muscle meat, including fish, is cooked, especially by frying and grilling. When these xenobiotic compounds enter the organism, they may be activated by metabolism into compounds with higher toxicity or carcinogenic potencial. Besides the enzymes of the phase I metabolism also the enzymes of the phase II metabolism mainly sulfotransferases (SULT) and N-acetyltransferases (NAT) may participate. Because these enzymes may be inducible their induction may be caused by other compounds present in food. Important inductors are some representatives of flavonoids - genistein, biochanin A and ß-naphtoflavone. These compounds have been proven to be able to to induce formation of sulfotransferases in vivo and in vitro conditions. An increased amount of enzymes may lead to the support of metabolic activation of procarcinogens, resulting in an increased formation of DNA aducts, causing development of carcinogenesis. For the research of induction of rat enzymes, rSULT and rNAT peptides were proposed that will be used for the production of antibodies suitable for their immunodetection.
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