Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy.

BackgroundMalaria infection can cause high oxidative stress, which could lead to the development of severe forms of malaria, such as pulmonary malaria. In recent years, the role of reactive oxygen species in the pathogenesis of the disease has been discussed, as well as the potential benefit of antioxidants supplementation. The aim of this study was to investigate the effects of N-acetyl cysteine (NAC) or mushroom Agaricus sylvaticus supplementation on the pulmonary oxidative changes in an experimental model of malaria caused by Plasmodium berghei strain ANKA.MethodsSwiss male mice were infected with P. berghei and treated with NAC or AS. Samples of lung tissue and whole blood were collected after one, three, five, seven or ten days of infection for the assessment of thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), nitrites and nitrates (NN) and to assess the degree of parasitaemia.ResultsAlthough parasitaemia increased progressively with the evolution of the disease in all infected groups, there was a significant decrease from the seventh to the tenth day of infection in both antioxidant-supplemented groups. Results showed significant higher levels of TEAC in both supplemented groups, the highest occurring in the group supplemented with A. sylvaticus. In parallel, TBARS showed similar levels among all groups, while levels of NN were higher in animals supplemented with NAC in relation to the positive control groups and A. sylvaticus, whose levels were similar to the negative control group.ConclusionOxidative stress arising from plasmodial infection was attenuated by supplementation of both antioxidants, but A. sylvaticus proved to be more effective and has the potential to become an important tool in the adjuvant therapy of malaria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0717-0) contains supplementary material, which is available to authorized users.

Oxidative stress has been implicated in the progression of HIV and other diseases. The authors of this article aimed to evaluate the effects of supplementation with a mushroom known to exhibit antioxidant properties on the oxidative status of children with HIV. Extensive measurements of oxidative stress markers and antioxidant capacity were obtained before and after 90 days of supplementation with the mushroom extract.

20Malaria still presents great epidemiologic importance by its high incidence in the 21 world and potential clinical severity. Plasmodium parasites are highly susceptible to 22 changes in the redox balance and the relationship between the redox state of the 23 parasite and host cells is very complex and involves nitric oxide (NO) synthesis. 24Thus, the present study is aimed at evaluating the effects of NO synthesis on the 25 redox status, parasitemia evolution and survival rate of Plasmodium berghei-26 infected mice. Two-hundred and twenty-five mice were infected with Plasmodium 27 berghei and submitted to the stimulation or inhibition of NO synthesis. The 28 stimulation of NO synthesis was performed through the administration of L-29 arginine, while its inhibition was made by the administration of dexamethasone.30 Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase 31 in the survival rate of P. berghei-infected mice and data suggested the participation 32 of oxidative stress in brain as a result of plasmodial infection, as well as the 33 inhibition of brain NO synthesis, which promoted survival rate of almost 90% of the 34 animals until the 15 th day of infection, with possible direct interference of ischemia 35 and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of 36 iNOS caused a decrease of parasitemia and increased survival rate of infected 37 animals, suggesting that the synthesis of NO may stimulate a series of 38 compensatory redox effects that, if overstimulated, may be responsible for the 39 onset of severe forms of malaria. 40 Plasmodium berghei, Inducible nitric oxide synthase, parasitemia, survival rate. 42 43 93Moreover, in response to the infection, activated macrophages and 94 neutrophils act as the natural defense mechanism of the host organism and these 95 generate a large amount of free radicals by activation of respiratory burst, causing 96 an imbalance between the formation of oxidant species and the activity of 97 antioxidants. This imbalance triggers the oxidative stress, being an important 98 mechanism of human host in response to microbial infections that, in the case of 99 malaria, can lead to the death of parasites.

The present study aimed to evaluate the effects of dexamethasone 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 subjected to 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 the data suggested the participation of oxidative stress in the brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted the 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 brain iNOS by dexamethasone caused a decrease in parasitemia and increased the survival rate of infected animals, suggesting that NO synthesis may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.