In vitro effects of the citrus flavonoids diosmin, naringenin and naringin on the hepatic drug-metabolizing CYP3A enzyme in human, pig, mouse and fish.
Flavonoids are known to have effects on cytochrome P450 enzymatic activity. However, little effort has been made to examine species differences and the relevance of studies on mammalian and fish microsomes so that extrapolations can be made to humans. Therefore, the effects of several naturally occurring flavonoids on the activity of CYP3A-dependent 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) were evaluated in human, pig, mouse, and juvenile rainbow trout sources of hepatic microsomes. Each was exposed to three concentrations (1, 10, and 100μM) of diosmin, naringin, and naringenin. Naringenin competitively inhibited BFCOD activity (Ki values were 24.6μM in human, 15.6μM in pig, and 19.6μM in mouse microsomes). In fish, BFCOD activity was inhibited in a noncompetitive manner (Ki=7μM). Neither diosmin nor naringenin affected BFCOD activity in hepatic microsomes from the studied model organisms. These results suggest that dietary flavonoids potentially inhibit the metabolism of clinical drugs.
University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25 Vodnany, Czech Republic. Electronic address: vburkina@frov.jcu.cz.
Viktoriia
V
Burkina
University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25 Vodnany, Czech Republic. Electronic address: vzlabek@frov.jcu.cz.
Vladimir
V
Zlabek
Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Department of Production Animal Clinical Sciences, P.O. 8146 Dep., N-0033 Oslo, Norway. Electronic address: ruth.halsne@nmbu.no.
Ruth
R
Halsne
Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Department of Production Animal Clinical Sciences, P.O. 8146 Dep., N-0033 Oslo, Norway. Electronic address: erik.ropstad@nmbu.no.
Erik
E
Ropstad
University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25 Vodnany, Czech Republic; Swedish University of Agricultural Sciences, Uppsala BioCenter, Department of Food Science, P.O. Box 7051, SE-750 07 Uppsala, Sweden. Electronic address: Galia.Zamaratskaia@slu.se.
Galia
G
Zamaratskaia
D000818:Animals; D002957:Citrus / Q000737:chemistry; D003374:Coumarins / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D004145:Diosmin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D017686:Oncorhynchus mykiss; D013045:Species Specificity; D013552:Swine
C419147:7-benzyloxy-4-trifluoromethylcoumarin; D003374:Coumarins; D004791:Enzyme Inhibitors; D044950:Flavanones; D004145:Diosmin; D051544:Cytochrome P-450 CYP3A; C005273:naringenin; C005274:naringin
CYP3A; Diosmin; Diosmin (PubChem CID: 5353588); Inhibition; Naringenin; Naringenin (PubChem CID: 932); Naringin; Naringin (PubChem CID: 25075)