Abstract
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.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / drug effects
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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ATP Binding Cassette Transporter, Subfamily B, Member 2 / drug effects
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ATP-Binding Cassette Transporters / drug effects*
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Cell Line
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Chagas Disease / drug therapy*
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Chagas Disease / metabolism
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Humans
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Macrophages / drug effects*
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins / metabolism
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Nitroimidazoles / pharmacology
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Nitroimidazoles / therapeutic use*
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Trypanocidal Agents / pharmacology
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Trypanocidal Agents / therapeutic use*
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Up-Regulation
Substances
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ABCB1 protein, human
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ABCC2 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins
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Nitroimidazoles
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TAP1 protein, human
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Trypanocidal Agents
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benzonidazole