title: Efficacy of pentavalent antimony, amphotericin B, and miltefosine in Leishmania amazonensis-infected macrophages under normoxic and hypoxic conditions.
abstract: Recently, our group demonstrated that mouse lesions infected with Leishmania amazonensis are hypoxic. Evidence indicates the negative impact of hypoxia on the efficacy of a variety of chemotherapeutic agents against tumors, fungi, bacteria, and malaria parasites. In the present study, comparison of the effect of antileishmanial drugs on L. amazonensis-infected macrophages under normoxic and hypoxic conditions was performed. We compared the effect of 5% oxygen tension with a tension of 21% oxygen on peritoneal murine macrophage cultures infected with the parasite and treated with glucantime, amphotericin B, or miltefosine. Analysis of the infection index (percentage of infected macrophages x number of amastigotes per macrophage), dose-dependent efficacy of drugs, and IC(50) values demonstrated that hypoxia conferred a small, but significant, resistance to all 3 antileishmanial drugs. The present finding suggests that in vitro assays under hypoxia should not be neglected in drug studies.
authors.affiliation: Departamento de Parasitologia, Instituto de Biologia, Universidade Estadual de Campinas, Cx. Postal 6109, Campinas, SP, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: Ayres
authors.forename: L A
authors.initials: LA
authors.lastname: Pinto
authors.forename: S
authors.initials: S
authors.lastname: Giorgio
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000469:parasitology*; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B; D010100:Oxygen