The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro.
Protective immune mechanisms to the asexual erythrocytic stages of the malaria parasite Plasmodium chabaudi AS strain include antibody-independent mechanisms. Nitric oxide (NO) is produced during the infection and indirect evidence suggests that it can contribute to the antiparasitic mechanisms. We examined the effect of an NO producer, S-nitroso-acetyl-penicillamine (SNAP), on the growth and survival in vitro of P. chabaudi AS, P. berghei and P. falciparum. Growth of the parasites was monitored by the uptake of tritiated hypoxanthine and, in the case of P. falciparum, by morphological examination in stained blood smears. DL-penicillamine and sodium nitrite, as controls, had no inhibitory activity at the concentrations used. The results showed that at SNAP concentrations of approximately 182 microM and above NO was cytotoxic to P. falciparum but, at lower concentrations, there was a cytostatic effect and some parasites resumed growth and division after NO production had ceased. Rings were less susceptible to NO effects than later stages in the asexual cycle. The antimalarial activity of NO from SNAP also extended to the rodent parasites but, under the experimental conditions used, they were less sensitive than the human species. In the cultures of P. chabaudi, increasing the numbers of noninfected erythrocytes present did not diminish the antimalarial activity of SNAP, suggesting that here at least haemoglobin was not scavenging NO significantly.
Balmer
P
P
Department of Vetinary Parisitology, University of Glasgow, UK.
Phillips
H M
HM
Maestre
A E
AE
McMonagle
F A
FA
Phillips
R S
RS
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D008288:Malaria / Q000097:blood / Q000469:parasitology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D018512:Parasitemia; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D016788:Plasmodium chabaudi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014316:Tritium
D000962:Antimalarials; C110881:S-nitro-N-acetylpenicillamine; D014316:Tritium; D019271:Hypoxanthine; D009569:Nitric Oxide; D010396:Penicillamine