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 × number of amastigotes per macrophage), dose-dependent efficacy of drugs, and IC₅₀ 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.