INHIBITION OF NITRIC OXIDE SYNTHESIS PROMOTES INCREASED MORTALITY DESPITE REDUCTION OF PARASITEMIA IN Plasmodium berghei-INFECTED MICE

Backgrounds: Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. Methods: To investigate the NO synthesis inhibition on the oxidative changes induced by Plasmodium berghei infection in mice, malaria was induced in 150 animals, of which 75 animals were treated with NO inhibitor L-NAME; the remaining are sham controls. All animals underwent euthanasia after 1, 5, 10, 15 or 20 days after the infection for the collection of lungs, brain, and blood. Parasitemia was determined and the survival of the animals evaluated. Tissue samples were assayed for nitrites and nitrates (NN), thiobarbituric acid reactive substances (TBARS), and total Trolox equivalent antioxidant capacity (TEAC). A histopathological study was performed. Results: Mortality rates in the L-NAME were always higher in relation to the controls. In brains, NN was lower in groups L-NAME. Parasitemia and its progression rate were greater in control groups. From the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. Conclusions: Anti-inflammatory and hemodynamic effects of NO surpasses its pro-oxidant role in murine malaria. Backgrounds: Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. Methods: To investigate the NO synthesis inhibition on the oxidative changes induced by Plasmodium berghei infection in mice, malaria was induced in 150 animals, of which 75 animals were treated with NO inhibitor L-NAME; the remaining are sham controls. All animals underwent euthanasia after 1, 5, 10, 15 or 20 days after the infection for the collection of lungs, brain, and blood. Parasitemia was determined and the survival of the animals evaluated. Tissue samples were assayed for nitrites and nitrates (NN), thiobarbituric acid reactive substances (TBARS), and total Trolox equivalent antioxidant capacity (TEAC). A histopathological study was performed. Results: Mortality rates in the L-NAME were always higher in relation to the controls. In brains, NN was lower in groups L-NAME. Parasitemia and its progression rate were greater in control groups. From the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. Conclusions: Anti-inflammatory and hemodynamic effects of NO surpasses its pro-oxidant role in murine malaria