The Effects of Splenectomy on Pattern of Nitric Oxide Induction and Pathogenesis of Rodent Malaria Caused by Plasmodium berghei Infection

Abstract

Background and Aims: The aim of this study is to clarify nitric oxide (NO)-production by spleen and the importance of spleen in malaria infection in murine model.
 Materials and Methods: Thirty outbred NMRI female mice were divided into four groups, Group I: No intervention (Healthy control), Group II: With splenectomy (Healthy test), Group III: No intervention, Inoculation of contaminated blood (Infected control), Group IV: With splenectomy, inoculation of contaminated blood (Infected test). The Parasitemia was counted every other day through Giemsa stain examination of animal blood. The parasitemia and survival rates, hepatosplenomegaly and body weight were recorded. After terminal anesthesia, plasma and liver/spleen suspensions were assessed by the Griess micro assay for measurement of NO-levels.
 Results: At the end of the experiment (on day 16), the parasitemia was 26.99±0.46 % among the group of non-splenectomized animals (Group III) compared with 31.25±0.72% among the group of splenectomized animals (Group IV). The average parasitemia among the groups at the end of the experiment was statistically significant (Group III, Group IV: p= 0.0002). Survival rate was statistically significant (p<0.0001). NO concentrations in plasma, liver and spleen were determined. The amount of NO in plasma increased significantly in the infected groups (p=0.0003).
 Conclusions: Although, splenectomy decreased immune function against rodent malaria, it did not solely changed the pattern of antimalarial activity via NO-pathway. It is concluded that NO possibly comes from several sources rather than spleen during rodent malaria disease and is released into circulation, which may replace NO shortage by splenic cells to combat malaria parasites.

Nitric Oxide Balance in Health and Diseases: Implications for New Treatment Strategies

“…Infection in humans and experimental animals significantly increases in systemic NO production, when determined by measurement of NO oxidation end-products (nitrite and nitrate) in plasma and urine [68]. In animal models, infections, such as leishmaniasis and toxoplasmosis, as well as tuberculosis in humans, have shown to have elevated expression of NOS-2 and NO production [69,70]. Possibly, there is a correlation between NO production and the host ability to contain microbial proliferation, due to dramatic increases in microbial burden as a result of abrogation of inducible NOS activity [71,72].…”

“…promote persistent asymptomatic latent infection. However, reactivation of some organisms has been induced in experimental models, such as Leishmania major, T. gondii, M. Tuberculosis, or Epstein -Barr virus, due to NO synthesis inhibition [70], indicating the major role of NO in latent infections.…”