Dano pulmonar durante a Malaria causada pelo Plasmodium berghei ANKA: investigando o potencial protetor do ômega 3 rico em DHA

Abstract

In the 21st century, malaria is still one of the greatest scourges of humanity, being responsible for thousands of clinical cases and deaths around the world. Mostly related to Plasmodium falciparum infections, deaths are associated with multiple pathogenic events that occur systemically in organs such as the brain, lungs, kidneys and liver. In contrast to what is observed for cerebral malaria, acute respiratory distress syndrome (ARDS) occurs more frequently in adults than in children and is considered an important complication of malarial infection, which can lead to death. Among the factors that contribute to pulmonary involvement, the secretion of inflammatory mediators, endothelial vascular permeability and adherence of parasitized red blood cells to endothelial capillaries stand out. Fish oil has been widely studied for its potential to modulate the immune response, being indicated as a possible alternative in the treatment of ARDS. Thus, this study aims to evaluate the protective role of fish oil rich in DHA at the pulmonary level during experimental malaria, for this purpose, C57BL/6 mice were prophylactically treated with 3.0 and 6.0 g/Kg of DHA in fish oil for 15 days, followed by infection with Plasmodium berghei ANKA. The animals were evaluated daily for the clinical profile, being euthanized on the 7th or 12th day for evaluation of the histopathological profile of the lungs, evaluation of the cytokine profile, occurrence of vascular permeability, edema and cellular profile. It was possible to observe that the treated animals showed a significant increase in their survival, as well as a preservation of clinically evaluated motor activities. Likewise, blood-alveolar barriers were maintained and pulmonary edema was reduced, which are pathological characteristics of pulmonary involvement during severe malaria. When analyzing pro and anti-inflammatory cytokines, there was a decrease in inflammatory cytokines when compared to the only infected group and an increase in IL-10 in treated groups. Analysis of the cellular phenotypic profile showed a decrease in total leukocytes as well as a decrease in CD8 T lymphocytes in previously treated animals, as well as a modulation in the activation of macrophages and dendritic cells. The histopathology of the treated animals corroborated the study, demonstrating a decrease in pulmonary edema, preservation of vascular permeability and absence of hemorrhage.