In Vitro Activity of Riboflavin against the Human Malaria Parasite Plasmodium falciparum
AUTOR(ES)
Akompong, Thomas
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=89633Documentos Relacionados
- Molecular targets of 5-fluoroorotate in the human malaria parasite, Plasmodium falciparum.
- Comparative Genomics of Transcriptional Control in the Human Malaria Parasite Plasmodium falciparum
- Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum.
- Gametocytocidal Activity and Synergistic Interactions of Riboflavin with Standard Antimalarial Drugs against Growth of Plasmodium falciparum In Vitro
- Targeting the Shikimate Pathway in the Malaria Parasite Plasmodium falciparum