Gold nanoparticles impair the development of pathophysiologic aspects associated with severe malaria

Falciparum malaria is a parasitic disease that can progress to cerebral malaria what could be associated with malaria-acute kidney injury (MAKI) and malaria-associated acute respiratory distress syndrome (MA-ARDS). Gold nanoparticles (AuNPs) appear as potential therapeutic agents in inflammatory diseases because of its anti-inflammatory effect. We aimed to verify the possible effect of AuNPs in severe malaria treatment. For this, C57BL/6 mice were infected with P. berghei ANKA and treated daily with AuNPs (10µg/kg) (CEUA-UFRJ 032/23). We observe that infection induced spleen (2,4-fold), brain (1,26-fold), lung (1,18-fold) and kidney (1,12-fold) hypertrophy which was prevented by AuNPs administration. AuNPs treatment increased survival of infected mice, reaching 26 days p.i., instead of 10 days. This increase was not associated with a decrease in parasitemia levels, since it courses linearly with time. Infection induced an increase in the spleen INFg and IL-17 producing CD4+ T cells, which was prevented by AuNPs treatment. AuNP-treated mice had increased IL-4 producing CD4+ T cells frequency. PbA infection induced a 2-fold increase on BBB permeability and cognitive damage on infected mice. Regarding MA-ARDS, infection induced intense inflammatory cell recruitment and higher diffuse alveolar damage. AuNPs treatment prevented all brain and pulmonary malaria-induced injuries. In MAKI, infection induced a local increase on CD4+ T cells producing INFg and IL-17 and reduced CD4+ T cells producing IL4+. Treatment with AuNP changed this profile by reducing Th1/Th2 ratio. There was a decrease on glomerular filtration rate and urinary flow of infected animals accompanied by an increase on plasma creatinine and urea. Bowman’s capsule space was also decreased by infection. None of these parameters were avoided by AuNP treatment. On the other hand, AuNPs treatment prevented infection-induced decrease in protein uptake by the proximal tubule cells (2,6-fold n=6) as well as reduced urinary excretion of proteins. Moreover, treatment ameliorated urinary γGT enzyme activity (1,15-fold n=12). In agreement, infected animals treated with AuNPs had smaller cortical interstitial space (9,91 times n= 3) and a reduced collagen deposition (7,34 times n=3), when compared to untreated infected mice. Together, our results bring AuNPs as a potential therapeutic agent, opening new perspectives for severe malaria treatment.