Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and UGT2B7.
Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.
Kuno
Nayumi
N
Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Mizutani
Takaharu
T
D000548:Amaranth Dye / Q000494:pharmacology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001391:Azo Compounds / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology; D002417:Cattle; D004396:Coloring Agents / Q000494:pharmacology*; D065637:Cytochrome P-450 CYP2A6; D004923:Erythrosine / Q000494:pharmacology; D005505:Food Coloring Agents / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007203:Indigo Carmine / Q000494:pharmacology; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009282:Naphthalenesulfonates; D013329:Structure-Activity Relationship; D013645:Tartrazine / Q000494:pharmacology
D001391:Azo Compounds; D001557:Benzenesulfonates; D004396:Coloring Agents; D005505:Food Coloring Agents; D009282:Naphthalenesulfonates; C005915:Allura Red AC Dye; D000548:Amaranth Dye; D007203:Indigo Carmine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; C110655:UDP-glucuronosyltransferase, UGT1A6; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C006796:brilliant blue; C005842:6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt; D013645:Tartrazine; D004923:Erythrosine; C576297:ponceau 4R