Up-regulation of ATP-binding cassette transporters in the THP-1 human macrophage cell line by the antichagasic benznidazole

PERDOMO, VIRGINIA G.; RIGALLI, JUAN P.; LUQUITA, MARCELO G.; PELLEGRINO, JOSÉ M.; RUIZ, MARÍA LAURA; CATANIA, VIVIANA A.

MEMóRIAS DO INSTITUTO OSWALDO CRUZ.

FUNDACO OSWALDO CRUZ

Año: 2016 vol. 111 p. 707 - 711

0074-0276

The effect of benznidazole (BZL) on the expression and activity of P-glycoprotein (P-gp, ABCB1) and multidrug resistance-associated protein 2 (MRP2, ABCC2), the two major transporters of endogenous and exogenous compounds, was evaluated in differentiated THP-1 cells. BZL induced P-gp and MRP2 proteins in a concentration-dependent manner. The increase in mRNA levels of both transporters suggests transcriptional regulation. P-gp and MRP2 activities correlated with increased protein levels. BZL intracellular accumulation was significantly lower in BZL-pre-treated cells than in control cells. PSC833 (a P-gp inhibitor) increased the intracellular BZL concentration in both pre-treated and control cells, confirming P-gp participation in BZL efflux.