摘要：The
synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth,
erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset yellow
FCF, brilliant blue FCF, and indigo carmine. First, data confirmed that these dyes
were not substrates for CYP2A6, UGT1A6, and UGT2B7. ET inhibited UGT1A6
(glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone).
We showed the inhibitory effect of xanthene dye on human UGT1A6 activity. Basic
ET, PL, and RB in those food dyes strongly inhibited UGT1A6 activity, with IC50
values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile, AR of an acidic
xanthene food dye showed no inhibition. Next, we studied the inhibition of CYP3A4
of a major phase I drug-metabolizing enzyme and P-glycoprotein of a major
transporter by synthetic food dyes. Human CYP3A4 and P-glycoprotein were also
inhibited by basic xanthene food dyes. The IC50 values of these dyes to inhibit
CYP3A4 and P-glycoprotein were the same as the inhibition level of UGT1A6 by
three halogenated xanthene food dyes (ET, PL, and RB) described above, except AR,
like the results with UGT1A6 and UGT2B7. We also confirmed the noninhibition of
CYP3A4 and P-gp by other synthetic food dyes. Part of this inhibition depended upon the
reaction of 1O2 originating on xanthene dyes by light irradiation, because inhibition
was prevented by 1O2 quenchers. We studied the influence of superoxide dismutase
and catalase on this inhibition by dyes and we found prevention of inhibition by
superoxide dismutase but not catalase. This result suggests that superoxide anions,
originating on dyes by light irradiation, must attack drug-metabolizing enzymes. It is
possible that red cosmetics containing phloxine, erythrosine, or rose bengal react with
proteins on skin under lighting and may lead to rough skin.
