title: Up-regulation of ATP-binding cassette transporters in the THP-1 human macrophage cell line by the antichagasic benznidazole.
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.
authors: Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.
authors: Virginia G
authors: VG
authors: Perdomo
authors: Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.|University of Heidelberg, Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg, Germany.
authors: Juan P
authors: JP
authors: Rigalli
authors: Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.
authors: Marcelo G
authors: MG
authors: Luquita
authors: Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.
authors: José M
authors: JM
authors: Pellegrino
authors: Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.
authors: María Laura
authors: ML
authors: Ruiz
authors: Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Argentina.
authors: Viviana A
authors: VA
authors: Catania
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2 / Q000187:drug effects; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects*; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C073119:TAP1 protein, human; C009999:benzonidazole