Oxidant-mediated damage of Leishmania donovani promastigotes

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Abstract
Dissemination of Leishmania within the host [mammal] is related to parasites undergoing unchecked proliferation. The effects of oxidant generating systems on promastigote multiplication by direct determination of organism proliferation and the incorporation of [3H]uracil into promastigote nucleoprotein. These 2 parameters correlated closely as measures of organism replication as demonstrated by parallel suppression of them by the protein synthesis inhibitors puromycin and cycloheximide and the nucleic acid synthesis inhibitors actinomycin D and mitomycin C. Promastigotes showed dose-related susceptibility to reagent and generated H2O2 as reflected in quantitatively similar decreases in multiplication and [3H]uracil incorporation. These effects were specific for H2O2 as catalase abrogated the dimunition in multiplication. The generation of superoxide anion by acetaldehyde-xanthine oxidase (10 mU/ml) did not alter promastigote replication or nucleoprotein synthesis. Evidently, L. donovani promastigotes are damaged by H2O2 and the incorporation of [3H]uracil into promastigote nucleoprotein may be useful for studying the interaction of this parasite with host effector cells.

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