title: The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate.
abstract: Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL) with low efficacy and resistance is emerging. CL is increased significantly in respect to incidence rate and expanding to new foci. In the present study, the effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was evaluated using colorimetric assay (MTT) and in a macrophage model, respectively. Verapamil, as a calcium channel blocker, affects drug uptake by preventing of drug efflux from the cells. In promastigote form, several concentrations of MA with or without verapamil showed significant decrease (P < 0.05) in optical density. The overall mean IC₅₀ value with combination of MA plus verapamil (IC50 = 116.03 μg/ml) was significantly less than MA (IC50 = 225.14 μg/ml) alone (P < 0.05) for promastigote stage. Similarly, the amastigote stage was more susceptible to treatment with MA plus verapamil to that of MA alone (P < 0.05). Analysis of overall effect of different concentrations of MA alone, compared with combination of MA plus verapamil by mean infection rate of amastigotes in each macrophage showed a significant difference (P < 0.05).These findings indicated some degree of synergistic effects between MA and verapamil on in vitro susceptibility of L. tropica to MA. Further works are required to evaluate this synergistic effect on animal model or volunteer human subjects.
authors.affiliation: School of Medicine, Hormozgan University of Medical Sciences, 761-6666367 Bandarabbas, Iran.
authors.forename: Azar
authors.initials: A
authors.lastname: Shokri
authors.forename: Iraj
authors.initials: I
authors.lastname: Sharifi
authors.forename: Ali
authors.initials: A
authors.lastname: Khamesipour
authors.forename: Nozar
authors.initials: N
authors.lastname: Nakhaee
authors.forename: Majid
authors.initials: M
authors.lastname: Fasihi Harandi
authors.forename: Jafar
authors.initials: J
authors.lastname: Nosratabadi
authors.forename: Maryam
authors.initials: M
authors.lastname: Hakimi Parizi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Barati
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003124:Colorimetry; D004195:Disease Models, Animal; D004357:Drug Synergism; D020128:Inhibitory Concentration 50; D007895:Leishmania tropica / Q000187:drug effects* / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D002121:Calcium Channel Blockers; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D014700:Verapamil