2006 Volume 52 Issue 5 Pages 549-557
We have reported that erythrosine (ET), a xanthene dye, inhibited uridine 5-diphosphate (UDP)-glucuronosyltransferase 1A6 (UGT1A6). In order to clarify the structure-inhibition relationships of these xanthene dyes, the inhibitory effect of xanthene dye on human UGT1A6 activity was investigated, such as acid red (AR), ET, phloxine (PL), and rose bengal (RB). ET, PL, and RB strongly inhibited human UGT1A6 activity, with IC50 values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile, AR had almost no effect (IC50 value = 1.7 mM). ET, PL and RB have four halogen atoms on their xanthene backbone, unlike AR. Meanwhile, some contrast media with high halogens on those aromatic compounds, such as ioxaglic acid, iodixanol, meglumine iotalamate, and diatriazole sodium, did not inhibit human UGT1A6 activity. These results suggest that halogens enhance the inhibitory effect of xanthene dyes. In this study, it was proved that xanthene dyes had an inhibitory effect on human UGT1A6 activity by the combination of xanthene structure and halogens on its. Part of this inhibition by xanthene dyes depends the reaction of 1O2 originated on xanthene dyes by light irradiation, because the inhibition was prevented by 1O2 quenchers, such as NaN3 and histidine, and in the dark.
