Add time:07/24/2019         Source:sciencedirect.com

Drugs currently available for visceral leishmaniasis treatment are potentially toxic, have to be administered by parenteral route and frequently give rise to drug resistance, due to the involvement of P-glycoproteins (P-gp) in Leishmania. The purpose of this study was to investigate a possible inhibitory effect of 2n-propylquinoline (2nPQ) on P-gp activity. 2nPQ is a new oral anti-leishmanial drug that has demonstrated its efficacy in BALB/c infected mice with Leishmania donovani [Antimicrob. Agents Chemother. 37 (1993) 859]. Rat everted gut sacs and human intestinal Caco-2 cell lines were used to study the effect of 2nPQ on P-gp activity. Our results demonstrate an inhibitory effect of 2nPQ on the P-gp activity with two P-gp substrates (rhodamine 123 and digoxin), two P-gp inhibitors (cyclosporin A and verapamil), and in two different species. Alone or associated with other active drugs, 2nPQ would be very useful to control Leishmania Multi-Drug-Resistance and intestinal P-gp in humans with kala-azar.Index Descriptors and Abbreviations: VL, visceral leishmaniasis; 2nPQ, 2n-propylquinoline; P-gp, P-glycoprotein; MDR, Multi-Drug-Resistance; Caco-2 cells, human colon adenocarcinoma cell line; BALB/c, Consanguine mouse; HIV, human immunodeficiency virus; DMEM, Dulbecco’s modified Eagle’s medium; PBS, phosphate-buffered salt Galipea longiflora, Rutaceae plant rat; everted gut sacs; LD50, lethal dose 50.

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