The role of nitric oxide and its up/downstream molecules in malaria: cytotoxic or preventive?

ABSTRACT

The current study investigated the involvement of nitric oxide (NO) and related molecules in malaria target organs of outbred MF1 mice during lethal Plasmodium berghei and non-lethal P. c. chabaudi infections, in order to evaluate whether changes in NO production are beneficial or detrimental to the host. A number of methods have been applied to test this hypothesis, including Griess microassay, electrochemical assay, RT-PCR and Western blot. The results show that reactive nitrogen intermediate (RNI) accumulation, in vitro levels of endogenous NO production, inducible nitric oxide synthase (iNOS) mRNA induction and NOS protein expression altered during murine malaria. The changes depended upon the tissue, the day of infection, the degree of parasitemia, the strain of Plasmodia and the method of measuring NO biosynthesis. Differences in the pathology of two strains of Plasmodia appear to depend more on the strain of parasite rather than the strain of host. The involvement of NO and its up/downstream molecules in murine malaria are specified to host/parasite combinations and it is influenced by the method used to assess NO. The anti-parasitic function against Plasmodia did not relate only to NO in this study, but a complex process consisting of NO and other immune factors is required to resolve the parasite. Selective delivery of inhibitors and donors of NO synthesis in the tissues of the malarial host is indicated as a potential novel therapy to inhibit the parasite or prevent its pathological symptoms.