Augmented Oxygen-Dependent Killing of Leishmania.
Final technical rept. Jul 90-Jul 92,
ARMED FORCES INST OF PATHOLOGY WASHINGTON DC
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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.