Augmented Oxygen-Dependent Killing of Leishmania.
Abstract
This study examined the role of oxygen in amphotericin B-induced killing of Leishmania braziliensis panamensis promastigotes and Candida albicans. In the first phase of the study, we explored the effects of high oxygen tensions on the lethal effects of three reduction-oxidation cycling drugs: amphotericin B, menadione, and phenazine methosulfate. Promastigotes were exposed to the above drugs under normoxic, hyperoxic (100% 02 at 101.3 kPa), ot hyperbaric hyperoxic (100% 02 at 253.3 kPa) conditions. After 24 h incubation at 27 deg C, viable promastigotes stained with fluorescein diacetate and were counted using epifluorescence microscopy. Hyperbaric hyperoxia alone (PO2 = 229 kPa) was as effective as AmB alone (0.2 uM); both killed 80% of the original inoculum. AmB killed more promastigotes in a hyperbaric hyperoxic environment than in normoxic (PO2 = 21.1 kPa) or hyperoxic conditions (PO2 = 91.7 kPa). High oxygen tensions did not alter the lethal effects of either menadione or phenazine methosulfate. In the second phase of the study, the effects of hypoxia on AmB killing in Leishmania and yeast cells were investigated. Leishmania promastigotes were exposed to AmB (0.1 and 1.0 uM) in media with dissolved PO2s of 22 mmHg (hypoxia) and 150 mmHg (normoxia) for two h at 27 deg C. Following incubation, promastigotes were stained as above and viable organisms counted. Promustigote, hyperoxia, hyperbaric hyperoxia, amphotericin B, Leishmania.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 30, 1992
- Accession Number
- ADA254943
Entities
People
- Brandon Wilson
- D. W. Criswell
- K. H. Muhvich
- L. H. Anderson
- R. T. Howard
Organizations
- Armed Forces Institute of Pathology