Deferoxamine inhibition of malaria is independent of host iron status

Journal Article · Fri Jul 01 04:00:00 EDT 1988 · J. Exp. Med.; (United States)

DOI:https://doi.org/10.1084/jem.168.1.375· OSTI ID:6922343

Hershko, C; Peto, T E

The mechanism whereby deferoxamine (DF) inhibits the growth of malaria parasites was studied in rats infected with Plasmodium berghei. Peak parasitemia was 32.6% (day 14) in untreated controls and 0.15% (day 7) in rats receiving 0.33 mg/g in 8 hourly DF injections, subcutaneously. DF inhibition of parasite growth was achieved without any reduction in transferrin saturation or hemoglobin synthesis and with only a partial (56%) depletion of hepatic iron stores. Dietary iron depletion resulted in anemia (hematocrit 25 vs. 46%), microcytosis (MCV 54 vs. 60 fl), and reduced transferrin saturation (17 vs. 96%) without any effect on infection (peak parasitemia 30 vs. 36%). Similarly, parenteral iron loading with ferric citrate over 10 d (75 mg iron/kg) failed to aggravate infection. In a search for evidence of direct interaction between DF and parasitized erythrocytes, gel filtration and ultrafiltration was performed on hemolysates obtained from in vivo /sup 59/Fe-labeled parasitized erythrocytes. This showed that 1.1-1.9% of the intracellular radioiron was located in a chelatable, labile iron pool. Incubation of intact cells with 0-500 microM DF resulted in a proportional increase in intracellular iron chelation, and the chelation of all available labile intracellular iron was completed within 6 h. These observations indicate that the severity of P. berghei infection in rats and its in vivo suppression by DF are independent of host iron status and suggest that DF inhibition of malaria involves intracellular chelation of a labile iron pool in parasitized erythrocytes.

• Research Organization: John Radcliffe Hospital, Oxford (England)
• OSTI ID: 6922343
• Journal Information: J. Exp. Med.; (United States), Journal Name: J. Exp. Med.; (United States) Vol. 168:1; ISSN JEMEA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANEMIAS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CHELATING AGENTS
DAYS LIVING RADIOISOTOPES
DEFEROXAMINE
DIGESTIVE SYSTEM
DISEASES
ELEMENTS
ERYTHROCYTES
EVEN-ODD NUCLEI
FILTRATION
GLANDS
GLOBULINS
GLOBULINS-BETA
GROWTH
HEMIC DISEASES
INFECTIOUS DISEASES
INFECTIVITY
INHIBITION
INTERMEDIATE MASS NUCLEI
INVERTEBRATES
IRON
IRON 59
IRON ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIVER
MALARIA
MAMMALS
MATERIALS
METALLOPROTEINS
METALS
MICROORGANISMS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARASITES
PARASITIC DISEASES
PLASMODIUM
PROTEINS
PROTOZOA
RADIOISOTOPES
RATS
RETICULOCYTES
RODENTS
SEPARATION PROCESSES
SPOROZOA
SYMPTOMS
TRACER TECHNIQUES
TRANSFERRIN
TRANSITION ELEMENTS
VERTEBRATES