Avaliação da suplementação dietética do ômega 3 rico em DHA em camundongos C57BL/6 no curso da infecção experimental com P. berghei NK65: análise pulmonar e intestinal

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a complication of malaria that affects between 5% and 25% of infected adults and has a high mortality rate even with the use of antimalarial drugs. This syndrome is caused, among other factors, by an exacerbated immune response of the body to infection and can occur regardless of the species of infecting Plasmodium. However, no effective treatment for malaria-associated ARDS (MA-ARDS) has yet been recognized. In addition, it has been shown that malaria infection also affects the intestinal tract, resulting in intestinal lesions and disorders. Recently, our group demonstrated that supplementation with DHA-rich fish oil was able to minimize lung damage in mice infected with Plasmodium berghei ANKA, a strain that promotes intense inflammation and adhesion of parasitized erythrocytes and leukocytes to the vascular endothelium. However, it is not established whether supplementation with high doses of DHA has a protective effect against lung injury caused by other strains, such as P. berghei NK65 (PbN), which induces systemic inflammation without promoting exacerbated endothelial adhesion. Given the absence of specific therapies for MA-ARDS and the different pathogenic characteristics among strains, this study investigated whether DHA-rich fish oil is capable of modulating lung injury and intestinal changes caused by PbN infection in a murine model of malaria infection. For this purpose, female C57BL/6 mice were orally supplemented with 3 g/kg of DHA-rich omega-3 for 15 days prior to infection. Lung injury was assessed through histological analyses, evaluation of pulmonary edema occurrence, and alveolar-capillary permeability tests. Pro- and anti-inflammatory cytokine levels were measured in lung homogenate to evaluate the inflammatory response. Analyses were also performed on bronchoalveolar lavage fluid to determine total and differential cell counts, protein concentration, and hydrogen peroxide production to assess inflammation and oxidative stress. The phenotypic characterization of pulmonary immune cells was performed by flow cytometry. For the analysis of systemic inflammation, hematological analyses (complete blood count) and immunophenotyping of spleen cells were conducted. For the evaluation of the intestinal tract, morphological and functional analyses of the intestine were performed, including intestinal measurements and quantification of intestinal permeability. In the lungs, no statistically significant differences were observed between the DHA-supplemented group and the infected-only group. In contrast, supplementation with DHA-rich omega-3 prevented intestinal shortening and reduced, albeit not significantly, permeability. These results highlight the importance of considering differences in pathogenic profiles between Plasmodium strains when investigating nutritional or immunomodulatory approaches.