Effect of amphotericin B on parasitemia and survival of plasmodium berghei-infected mice.
Premature death of Plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. Amphotericin B has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study thus tested whether amphotericin B exerts a direct effect on Plasmodium falciparum and influences eryptosis of infected erythrocytes, parasitemia and host survival in murine malaria. To this end, human erythrocytes were infected in vitro with Plasmodium falciparum and mice were infected with Plasmodium berghei ANKA by in vivo intraperitoneal injection of parasitized murine erythrocytes (1x10(6)). Half of the infected mice received amphotericin B (1.5 mg/kg b.w. i.v.) from the 8(th) day of infection. Amphotericin B (> or = 1 microM) compromised the intracellular development of the parasite in human erythrocytes as evident from in vitro growth and DNA amplification assays. Amphotericin B further augmented the eryptosis of infected human erythrocytes. The administration of amphotericin B to infected mice tended to delay the increase of parasitemia and significantly delayed host death. All nontreated mice died from malaria within 27 days. In contrast, some 50% of amphotericin B-treated mice survived for more than 27 days after infection. In conclusion, amphotericin B augmented the suicidal death of infected erythrocytes and delayed the lethal course of malaria in Plasmodium berghei infected mice.
Siraskar
Balasaheb
B
Department of Physiology, University of Tübingen, Tübingen, Germany.
Ballal
Adil
A
Bobbala
Diwakar
D
Föller
Michael
M
Lang
Florian
F
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D017209:Apoptosis; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy* / Q000401:mortality; D010962:Plasmodium berghei / Q000187:drug effects*
D000981:Antiprotozoal Agents; D000666:Amphotericin B