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The malarial pigment in rat infected erythrocytes and its interaction with chloroquine. A Mössbauer effect study
Abstract:
Mössbauer studies of rat erythrocytes infected by Plasmodium berghei malaria parasites, using 57Fe-enriched rat red blood cells, were carried out in order to determine the physical parameters which characterize the malarial pigment iron and to test the effect of the widely used antimalaria drug, chloroquine, on these parameters. The iron in the malarial pigment which is derived from hemoglobin digestion by the intracellular parasite was found to be trivalent, high spin, with Mössbauer parameters which are significantly different from those of any known iron porphyrin containing compound. No difference was found between the parameters obtained in erythrocytes infected by drug-sensitive and drug-resistant strains of P. berghei, both before and after the treatment with chloroquine. The iron compound consists of microaggregates, about 30 A in diameter. These are somewhat larger in chloroquine-resistant strains and tend to increase in size in chloroquine-sensitive strains upon treatment with the drug. Mössbauer spectra of erythrocytes infected by a chloroquine-resistant strain revealed pigment iron in relative amounts invariable of those found in chloroquine-sensitive strains, demonstrating that drug-resistant parasites indeed digest hemoglobin.
Insights
Mössbauer studies reveal malarial pigment iron in Plasmodium berghei is trivalent and high spin. Chloroquine treatment did not alter iron parameters, indicating drug resistance does not affect hemoglobin digestion.
Area of Science:
- Biophysics
- Parasitology
- Hematology
Background:
- Malaria parasites digest host hemoglobin to obtain iron.
- The resulting malarial pigment's iron speciation and its response to antimalarial drugs are not fully understood.
- Understanding these properties is crucial for developing effective malaria treatments.
Purpose of the Study:
- To characterize the physical parameters of iron within malarial pigment in Plasmodium berghei-infected erythrocytes.
- To investigate the effect of chloroquine, a common antimalarial drug, on these iron parameters.
- To compare iron speciation in drug-sensitive and drug-resistant malaria strains.
Main Methods:
- Mössbauer spectroscopy was employed using 57Fe-enriched rat erythrocytes infected with Plasmodium berghei.
- Comparative analysis of Mössbauer parameters was performed on samples from drug-sensitive and drug-resistant strains.
- The impact of chloroquine treatment on infected erythrocytes was assessed.
Main Results:
- Malarial pigment iron was identified as trivalent, high spin, with unique Mössbauer parameters distinct from known iron porphyrins.
- No significant differences in iron parameters were observed between drug-sensitive and drug-resistant strains, or after chloroquine treatment.
- The iron compound exists as microaggregates (~30 Å), which were slightly larger in resistant strains and increased in size in sensitive strains upon chloroquine treatment.
- Pigment iron levels remained consistent in resistant strains, confirming hemoglobin digestion.
Conclusions:
- The iron in malarial pigment has distinct biophysical properties.
- Chloroquine efficacy is not directly related to alterations in malarial pigment iron speciation.
- Drug-resistant Plasmodium berghei strains effectively digest hemoglobin, similar to sensitive strains.