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 mala ria parasite Plasmodium chabaudi AS strain include antibody-independent mec hanisms. Nitric oxide (NO) is produced during the infection and indirect ev idence 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 tritiat ed hypoxanthine and, in the case of P. falciparum, by morphological examina tion in stained blood smears. dl-penicillamine and sodium nitrite, as contr ols, had no inhibitory activity at the concentrations used. The results sho wed that at SNAP concentrations of approximately 182 mu m and above NO was cytotoxic to P. falciparum but, at lower concentrations, there was a cytost atic effect and some parasites resumed growth and division after NO product ion had ceased. Rings were less susceptible to NO effects than later stages in the asexual cycle. The antimalarial activity of NO from SNAP also exten ded to the rodent parasites but, under the experimental conditions used, th ey were less sensitive than the human species. In the cultures of P. chabau di, increasing the numbers of noninfected erythrocytes present did not dimi nish the antimalarial activity of SNAP, suggesting that here at least haemo globin was not scavenging NO significantly.