The effect of combined therapy using rosuvastatin and dihydroarteminin in a pulmonary malaria mouse model.

Malaria can progress to malaria-associated ARDS (MA-ARDS), with a mortality rate of up to 80%. Since it is caused by sequestration of parasitized cells in the lung and a deregulated host immune response, the use of an antimalarial drug associated with an anti-inflammatory compound could improve MA-ARDS outcomes. We evaluated the effects of Rosuvastatin (ROSU), a statin with immunomodulatory properties largely used for treatment of cardiovascular diseases, and its association with dihydroartemisinin (DHA) in an experimental model. C57/BL6 mice were infected with Plasmodium berghei NK65, treated with ROSU(3mg/Kg), DHA(20mg/Kg) or (ROSU+DHA), and systemic and pulmonary parameters were evaluated. The anti-inflammatory potential of ROSU was confirmed by the 55.7% decrease in leukocyte counts 15 dpi. A single dose of ROSU increased the survival rate of infected animals by 39%, but was not able to reverse pulmonary edema 24 hours after treatment. When given separately, ROSU and DHA were able to keep normal globular concentration levels after 15 dpi. The antiparasitic effect of DHA was confirmed and DHA was able to partially normalize the RBC/hemoglobin count and hematocrit. A single dose of DHA maintained resistive and viscoelastic pressure similar to the control, however elastance could only be normalized with the combined treatment. The results are important to understand the effects of ROSU, DHA or ROSU+DHA in this model. And more importantly, we did not observe any deleterious e...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Mechanisms of Lung Injury and Repair Source Type: research