1921
Volume 45, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

Desferrioxamine (DFO) is an iron chelator that inhibits the in vitro and in vivo growth of rodent and human malarial parasites. Previous studies with this chelator have suggested that it might interfere with the intraerythrocytic growth of sp. by withholding iron from any of several essential iron-dependent parasite enzymes, including those involved in CO fixation, mitochondrial electron transport, pyrimidine synthesis, and the reduction of ribonucleotides for DNA synthesis. We studied the ultrastructural effects of DFO on synchronized cultures of to identify the specific site of action of this compound. Synchronized cultures of early rings or schizonts were exposed to 100 µM DFO for up to 48 hr, and fixed and processed at regular intervals for electron microscopy. Untreated cultures and cultures exposed to DFO saturated with Fe were processed at the same time. When DFO was added to synchronized cultures containing early rings, parasites developed normally until the late trophozoite stage, when all growth ceased. Ultrastructural lesions included the breakdown of the nuclear envelope into small membranous fragments and progressive vacuolization of the nucleoplasm. Other organelles, including food vacuoles and mitochondria, were not affected. The addition of DFO to synchronized cultures of schizonts had similar effects on nuclei of early schizonts, but little or no effect on mature schizonts and segmenters. Erythrocyte invasion by merozoites proceeded in the presence of the chelator. These findings support the hypothesis that DFO acts specifically during the late trophozoite/early schizont stage of parasite maturation by preventing nuclear division, an effect consistent with inhibition of the iron-dependent enzyme ribonucleotide reductase.

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/content/journals/10.4269/ajtmh.1991.45.593
1991-11-01
2017-09-23
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