Fig. 3.

The effects of P-gp and BCRP on [³H]nifurtimox accumulation. To assess the roles played by the ABC transporters, P-gp and BCRP, in the transport of nifurtimox, the accumulation of [³H]nifurtimox in confluent monolayers of hCMEC/D3 cells in 96 well plates was observed, with or without known transporter interacting drugs, in the presence of 0.05% DMSO. The P-gp substrate and inhibitor (dexamethasone and haloperidol respectively) caused no significant alteration in the accumulation of [³H]nifurtimox. ATP depletion caused a significant increase at all time points compared to both control data and P-gp inhibition (A). PhA and ko143 (a BCRP substrate and BCRP inhibitor respectively), caused a significant increase in [³H]nifurtimox accumulation in the cells compared to control data (***p < 0.001). The values were comparable to those generated by ATP depletion which also caused a significant increase compared to controls at all time points (**p < 0.01, ***p < 0.001) until the 30 minute time point when ATP depletion caused a significant increase in accumulation compared to both inhibitors (*p < 0.05) (B). All data expressed as mean ± S.E.M, n = 4–6 (plates), with 6 replicates (wells) per plate. Data were analyzed with SigmaPlot 11.0.