Food dyes as P-glycoprotein modulators

Abstract

The drug transporter P-glycoprotein (P-gp) is often investigated in drug-interaction studies because the activity is modulated by a wide variety of xenobiotics including drugs, herbal products, and food components. In this study, we tested six common arylsulfonate food dyes-allura red, carmoisine, ponceau 4R, quinolone yellow, sunset yellow, and tartrazine-as activators and inhibitors of P-gp activity in vitro. The dyes were studied as P-gp activators by measuring ATPase activity in P-gp-expressing membranes. Compared to verapamil, a known activator of P-gp, the six food dyes showed no stimulatory activity. The potential for these six food dyes to act as P-gp inhibitors was tested in an intracellular efflux assay with P-gp-expressing cells. Compared to GF120918, a known P-gp inhibitor, there was no inhibitory activity for these six food dyes. The six food dyes tested do not interact with P-gp in vitro and, therefore, are unlikely cause clinical drug-food dye interactions. Further investigation is necessary to determine whether these food dyes could interact with other drug transporters.

Keywords: Drug transporter; Food dye; P-glycoprotein.

Figure 1.

Arylsulfonate food dyes tested as P-gp substrates and inhibitors

Figure 2.. ATPase activity of verapamil in P-gp over-expressing membranes.

Stimulation of ATPase activity by test compound alone (closed circle; solid line) and test compound in the presence of P-gp inhibitor sodium orthovanadate (closed triangle; dashed line): known P-gp substrate verapamil (A) and food dyes allura red (B), carmoisine (C), ponceau 4R (D), quinolone yellow (E), sunset yellow (F), and tartrazine (G). ATPase activity of test compounds was tested in triplicate and repeated once (n = 3 with 2 replicates). Data are represented as % ATPase activity normalized to 200 μM verapamil (mean ± S.E.).

Figure 3.. Inhibition of P-gp transport in LLC-MDR1-WT cells.

Percent inhibition of rhodamine-123 transport by test compounds. Known P-gp inhibitors GF120918 (closed circle) and food dyes allura red (open circles), carmoisine (open square), ponceau 4R (open triangle), quinoline yellow (open upside-down triangle), sunset yellow (open diamond), and tartrazine (open hexagon). GF120918 inhibition was evaluated in triplicate and repeated 5 times (n = 3 with 6 replicates); food dyes were tested in triplicate and repeated twice (n = 3 with 3 replicates). Data represented as % inhibition relative to 1 μM GF120918 (mean ± S.E.).