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Antimicrobial Agents and Chemotherapy, January 2000, p. 88-96, Vol. 44, No. 1
Departments of Pathology and
Microbiology-Immunology, Northwestern University Medical School,
Chicago, Illinois 60611-3008,1 and
Department of Microbiology and Immunology, Stanford
University School of Medicine, Stanford, California
94305-51242
Received 20 April 1999/Returned for modification 18 June
1999/Accepted 15 October 1999
The human malaria parasite Plasmodium falciparum
digests hemoglobin and polymerizes the released free heme into
hemozoin. This activity occurs in an acidic organelle called the food
vacuole and is essential for survival of the parasite in erythrocytes. Since acidic conditions are known to enhance the auto-oxidation of
hemoglobin, we investigated whether hemoglobin ingested by the parasite
was oxidized and whether the oxidation process could be a target
for chemotherapy against malaria. We released parasites from their host
cells and separately analyzed hemoglobin ingested by the parasites from
that remaining in the erythrocytes. Isolated parasites contained
elevated amounts (38.5% ± 3.5%) of oxidized hemoglobin
(methemoglobin) compared to levels (0.8% ± 0.2%) found in normal, uninfected erythrocytes. Further, treatment of infected cells with the reducing agent riboflavin for 24 h decreased the parasite methemoglobin level by 55%. It also
inhibited hemozoin production by 50% and decreased the
average size of the food vacuole by 47%. Administration of riboflavin
for 48 h resulted in a 65% decrease in food vacuole size and
inhibited asexual parasite growth in cultures. High doses of riboflavin
are used clinically to treat congenital methemoglobinemia
without any adverse side effects. This activity, in conjunction with
its impressive antimalarial activity, makes riboflavin attractive as a
safe and inexpensive drug for treating malaria caused by P. falciparum.
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
In Vitro Activity of Riboflavin against the Human
Malaria Parasite Plasmodium falciparum
*
Corresponding author. Mailing address: Departments of
Pathology and Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611-3008. Phone: (312) 503-1443. Fax: (312) 503-0281. E-mail: t-akompong{at}nwu.edu.
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