The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro

Abstract

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.

Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection

“…Specifically, Rockett et al [6] found that low molecular weight Snitrosothiols (SNOs) displayed a 1,000-fold greater toxicity to Plasmodium falciparum than nitrate, which was 3-fold more toxic than nitrite. In addition at lower concentrations some NO x were cytostatic to P. falciparum [7,8]. In contrast to our knowledge of asexual parasites, the effects of NO x on mosquito-stage parasites are unknown.…”

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…However, the mechanism of protective immunity against malaria is poorly understood, and no particular specific immune response has been established as an essential or exclusive correlate of clinical protection. Early studies confirmed the importance of cellmediated immune pathways in the adaptive response against malaria [13,14], and evidenced the central role of CD4+ T cells in parasitemia clearance and host survival [15,16]. Following activation, CD4+ T cells proliferate rapidly and acquire critical effector functions; before undergoing a dramatic contraction phase after the peak of infection [17] to become established memory T cells.…”

Apoptosis-like death as a feature of malaria infection in mosquitoes

“…The complex relationship between NO and P. falciparum infections in the vertebrate host is still unresolved (Clark, Rockett and Burgner, 2003). It is likely that the bioavailability of NO in the vasculature of malaria-infected hosts is low, due to NO scavenging by haemoglobin and O 2 x , and there is evidence that NO does not have a killing effect on rodent-malaria (reviewed in Sobolewski et al 2005) although this conclusion is controversial (Balmer et al 2000). It appears that NO-derived products such as nitrosothiols, rather than NO itself, are toxic to the parasite (Rockett et al 1991).…”