Inhibition of nitric oxide synthesis promotes increased mortality despite the reduction of parasitemia in Plasmodium berghei-infected mice

Abstract

Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. 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 the NO inhibitor L-NAME; the remaining animals were sham controls. All animals underwent euthanasia 1, 5, 10, 15, or 20 days after infection for the collection of lungs, brain, and blood. Parasitemia was determined, and the survival of the animals was 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. Mortality rates in the L-NAME group were always higher than those in the controls. In the brain, NN was lower in the L-NAME group. Parasitemia and its progression rate were greater in the control group. By the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. In conclusion, the anti-inflammatory and hemodynamic effects of NO surpass its pro-oxidant role in murine malaria.

Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb

“…This hypothesis was verified by Moreira et al [13], who identified an increase in TEAC after the 10th day of treatment with dexamethasone, followed by an increase in survival and reduction in parasitemia of mice infected with P. berghei. Similar results were obtained during treatment with N-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide (NO) synthesis, with increased TEAC on the 20th day post P. berghei infection [14].…”

Potential Benefits of Lycopene Consumption: Rationale for Using It as an Adjuvant Treatment for Malaria Patients and in Several Diseases

“…Scientific evidence demonstrates that a specific RONS is particularly involved in the pathophysiology of this disease: NO [122,123]. It has been suggested that the low bioavailability of NO promotes oxidative stress in tissues such as the brain and lungs [124]. On the other hand, it has been shown that NO at high concentrations can kill Plasmodium [125,126].…”

Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy

“…According to Moreira et al [ 110 ], the inhibition of cerebral NO synthesis by dexamethasone increased the survival rate in 90% of animals until the 15th day of infection, followed by a significant reduction in parasitemia in mice infected with P. berghei. On the other hand, when NO synthesis is inhibited by Nω-nitro-L-arginine methyl ester (L-NAME), there is an increase in animal mortality, with a consequent reduction in parasitemia in P. berghei -infected mice, suggesting that the physiological effects of NO outweigh its pro-oxidant role in experimental malaria [ 111 ].…”