Influence of Synthetic and Natural Food Dyes on Activities of CYP2A6, UGT1A6, and UGT2B7

Abstract

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.

Inhibition Mechanism of UDP-Glucuronosyltransferase 1A6 by Xanthene Food Dyes

“…26) This indicates that inhibition is dependent upon a complexed-type reaction involving enzyme inactivation. In order to clarify the mechanisms, we studied the influence of 1 O 2 quenchers, such as NaN 3 , histidine, and β-carotene on glucuronidation inhibition by RB.…”

“…26) ET is a xanthene dyes and is highly halogenated. Therefore, we studied the inhibition of UGT1A6 by other two halogenated xanthene dyes, such as RB and PL, permitted food additive dyes, and ES and E5ic, non-permitted dyes, whose structures are shown in Fig.…”

“…23,24) Acetylcholineesterase and some microorganims, such as Escherichia coli, Staphylococcus aureus, and influenza virus, are inactivated, 17,18,22,25) therefore, it is possible that xanthene dyes inactivate drug-metabolizing enzymes. 26) In the previous study, we clarified that RB inhibited the activity of UGT1A6 and CYP2A6 by mixed-type inhibitory mechanism. 26) In this study, we clarified the structure-function-relationship of xanthene dyes and also suggested that inhibition depended upon light reaction by the generation of 1 O 2 on these dyes.…”

“…26) In the previous study, we clarified that RB inhibited the activity of UGT1A6 and CYP2A6 by mixed-type inhibitory mechanism. 26) In this study, we clarified the structure-function-relationship of xanthene dyes and also suggested that inhibition depended upon light reaction by the generation of 1 O 2 on these dyes. Fig.…”

In Vitro Screening Assay for Detecting Aromatase Activity Using Rat Ovarian Microsomes and Estrone ELISA

“…24) Erythrosine (0.1 mg/mg mitochondrial protein) completely inhibited mitochondrial respiration in the rat liver and kidney, 25) and glucuronidation of p-nitrophenol and androsterone. 26) Erythrosine may interact with DNA repair enzymes and/or with DNA, 27,28) and has estrogen-like growth stimulatory properties in human breast cancer cells, 28) but does not show mutagenicity or genotoxicity .29,30) Administrating of rose bengal in mice induced colloid goiters and thyroid adenomas 31) and decreased in serum levels of triiodothyronine and thyroxine. 32) Upon feeding of phloxine in male mice, body weight increased significantly, but phloxine is not carcinogenic.…”