Dihydromyricetin (DHM) is a natural flavonoid showing several health promoting effects such as protective activity during severe alcohol intoxication. The mechanism underlying the effects of DHM on alcohol metabolism is virtually unknown. The present paper is focused on clarifying the role of DHM in the liver alcohol elimination at its molecular level. First, impact of DHM on alcohol dehydrogenase (ADH) activity in vitro and the enzyme induction in vivo was examined. Neither the ADH activity nor the enzyme expression were influenced by DHM. Next, the effect of DHM during alcohol intoxication were studied on primary hepatocytes isolated from EtOH-premedicated and untreated rats. The viability of cells exposed to alcohol, estimated based on the released enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was slightly affected by DHM. Although the expected hepatoprotective effect of DHM was not fully achieved, DHM (in a concentration manner) proved to reduce the level of ROS/RNS in hepatocytes. However, no change in the rate of alcohol metabolism in vivo was found when rats were administered with a single or repeated dose of ethanol supplemented with DHM. In conclusion, the proposed positive effect of DHM during alcohol intoxication has not been proven. Moreover, there is no effect of DHM on the alcohol metabolism. The "hoped-for" DHM hepatoprotective activity can be attributed to the reduction of ROS/RNS levels in cells.

• MeSH
• Alcohol Dehydrogenase metabolism   MeSH
• Antioxidants pharmacology   MeSH
• Cytochrome P-450 CYP2E1 metabolism   MeSH
• Ethanol metabolism   MeSH
• Flavonols pharmacology   MeSH
• Hepatocytes drug effects   metabolism   MeSH
• Liver drug effects   metabolism   MeSH
• Cells, Cultured MeSH
• Inactivation, Metabolic MeSH
• Nitrosative Stress drug effects   MeSH
• Oxidative Stress drug effects   MeSH
• Rats, Wistar MeSH
• Reactive Nitrogen Species metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alcohol Dehydrogenase MeSH
• Antioxidants MeSH
• Cytochrome P-450 CYP2E1 MeSH
• dihydromyricetin MeSH Browser
• Ethanol MeSH
• Flavonols MeSH
• Reactive Nitrogen Species MeSH
• Reactive Oxygen Species MeSH

In recent years, the consumption and use of dietary supplements containing concentrated phytochemicals (e.g. flavonoids) increased dramatically. Flavonoids, as foreign compounds (xenobiotics), have great potential to modulate the activity of cytochrome P450s (CYPs), xenobiotic-metabolizing enzymes involved in the activation and detoxification of food and environmental carcinogens. Thus, the aim of this study was to investigate the effects of model glycosylated and deglycosylated flavonoids on CYPs in rat liver and small intestine, as the two main organs responsible for xenobiotic metabolism, after p.o. administration by gastric gavages. The effects of two glycosylated flavonoids (isoquercitrin, rutin) and their aglycone (quercetin) on CYPs were determined using Western blotting technique and specific activity assays with alkyl-resorufin derivatives. In liver microsomes, a considerable increase of all the measured marker activities (EROD, MROD, PROD) was observed only after isoquercitrin treatment. To evaluate the effects of flavonoids on CYPs along small intestine, the tissue was dissected into proximal (near pylorus), middle and distal parts. Of all the tested compounds, isoquercitrin was the most efficient CYP inducer, namely in the middle part of small intestine. Obtained data demonstrate the different effects of flavonoid glycosides and aglycone on CYP expression in rat liver and small intestine. Since these phytochemicals are xenobiotics, and thus they can increase the human risk of cancer development, their consumption in large quantities should be carefully considered.

• Keywords
• cytochrome P450, flavonoids, induction, liver, small intestine,
• Publication type
• Journal Article MeSH