Influence of paclitaxel on parasitemia and survival of Plasmodium berghei infected mice.
Paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. The present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of Plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of Plasmodium berghei infected mice. Phosphatidylserine exposing erythrocytes were identified utilizing annexin V binding and erythrocyte volume was estimated from forward scatter in FACS analysis. In vitro infection of human erythrocytes with P. falciparum increased annexin binding and decreased forward scatter, effects augmented in the presence of paclitaxel (> or = 0.01 microM). Paclitaxel (> or = 0.01 microM) significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia. In Plasmodium berghei infected mice parasitemia was significantly decreased (from 55.8% to 28.6% of circulating erythrocytes 20 days after infection) and mouse survival significantly enhanced (from 0% to 69.23% 25 days after infection) by administration of 8.5 mg/kg.b.w. of paclitaxel intraperitoneally from the eighth day of infection. In conclusion, paclitaxel decreases parasitemia and enhances survival of P. berghei infected mice, an effect, which may be due to stimulation of eryptosis and/or a direct toxic effect on the parasite.
Koka
Saisudha
S
Department of Physiology, University of Tubingen, Germany.
Bobbala
Diwakar
D
Lang
Camelia
C
Boini
Krishna M
KM
Huber
Stephan M
SM
Lang
Florian
F
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy / Q000401:mortality; D010962:Plasmodium berghei / Q000187:drug effects* / Q000502:physiology*
D017304:Annexin A5; D000962:Antimalarials; D017239:Paclitaxel