Efficacy of pentavalent antimony, amphotericin B, and miltefosine in Leishmania amazonensis-infected macrophages under normoxic and hypoxic conditions.
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.
Ayres
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DC
Departamento de Parasitologia, Instituto de Biologia, Universidade Estadual de Campinas, Cx. Postal 6109, Campinas, SP, Brazil.
Pinto
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LA
Giorgio
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S
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
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B; D010100:Oxygen