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Effect of dihydromyricetin on hepatic ethanol metabolism
Boubínová, Gabriela ; Hodek, Petr (advisor) ; Bebová, Michaela (referee)
Dihydromyricetin (DMH) is a natural flavonoid compound with positive effects on the human organism. In traditional Chinese medicine, plants containing DMH were used to treat liver diseases and to reduce alcohol intoxication. The effects of DHM on ethanol metabolism are not yet completely understood. Effects of DHM during alcohol intoxication were studied on primary hepatocytes of rats. DCFDA and DHR probes were used to prove that DHM (depending on concentration) reduces the number of reactive oxygen and nitrogen species in primary hepatocytes. However, the hepatoprotective effects of DHM were not achieved when presence of the alanine aminotransferase (ALT) was used to measure the damage of cells exposed to alcohol. Further, the effects of DHM on alcohol metabolism were studied in vivo. Rats were administered with single dose of ethanol or ethanol combined with DHM. Measured blood levels of ethanol and acetaldehyde show that DHM has no effects on the rate or levels of alcohol metabolism. The effects of DHM were also studied with repeated alcohol administration. In the group that was administered also DHM, increased blood levels of ethanol were measured. This points that DHM slow down the metabolic rate of ethanol. Obtained results did not prove any positive effects of DHM on alcohol metabolism....
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Interaction of flavonoid compounds with sulfotransferase 1A1
Bebová, Michaela ; Hodek, Petr (advisor) ; Černá, Věra (referee)
Increased attention has recently been paid to the natural polyphenolic compounds contained in food of plant origin. Flavonoids represent a large group of phytochemicals that are contained in many dietary supplements. Consumption of these products increases as new findings of beneficial effects on health are discovered. Using high doses of natural, but for the human body xenobiotic compounds may be associated with negative effects. Some flavonoids are modulators of enzymes involved in phase I and phase II biotransformation and their inhibition or induction may interfere with endogenous metabolism. In this study, the effects of selected flavonoid compounds dihydromyricetin (DHM) and myricetin (MYR) on the activity and expression of enzymes of phase II biotransformation, sulfotransferases 1A1 (SULT1A1), in liver and intestine of rats were investigated. SULT1A1 is significantly involved in the metabolic activation of xenobiotics. Thus, induction or stimulation by flavonoid compounds may potentiate the formation of carcinogens and increase the risk of developing cancer. As reference flavonoid compounds, biochanin A (BIA) and quercetin were additionally included in the study. Flavonoids were administered by gavage into the stomach of rats to study the potential interactions in vivo. Flavonoid DHM...
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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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