Inhibition Of Nitric Oxide Synthesis By Dexamethasone Increases Survival Rate In Plasmodium berghei-Infected Mice

Abstract

Malaria still presents great epidemiologic importance by its high incidence in the world and potential clinical severity. Plasmodium parasites are highly susceptible to changes in the redox balance and the relationship between the redox state of the parasite and host cells is very complex and involves nitric oxide (NO) synthesis. Thus, the present study is aimed at evaluating the effects of NO synthesis on the redox status, parasitemia evolution and survival rate of Plasmodium berghei-infected mice. Two-hundred and twenty-five mice were infected with Plasmodium berghei and submitted to the stimulation or inhibition of NO synthesis. The stimulation of NO synthesis was performed through the administration of L-arginine, while its inhibition was made by the administration of dexamethasone. Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase in the survival rate of P. berghei-infected mice and data suggested the participation of oxidative stress in brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted survival rate of almost 90% of the animals until the 15th day of infection, with possible direct interference of ischemia and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of iNOS caused a decrease of parasitemia and increased survival rate of infected animals, suggesting that the synthesis of NO may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.