Sodium perborate tetrahydrate modulates neuroinflammation and reduces Leishmania infantum infection in astrocytes

Abstract

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of genus Leishmania. Although the parasites are classically considered macrophage-resident pathogens, accumulating evidence suggests that Leishmania can cross the blood-brain barrier and induce neurological manifestations, referred to as cerebral leishmaniasis. Astrocytes, which are key regulators of central nervous system immune homeostasis, remain poorly characterized in the context of Leishmania infection. In this study, we investigated neuroimmune-based antileishmanial effects of sodium perborate tetrahydrate (SPT) in Leishmania infantum-infected murine astrocytes. SPT concentrations between 25 and 150 & micro;M maintained astrocyte viability above 90% for 24-72 h. Flow-cytometric analysis demonstrated that the astrocyte infection rate, which was approximately 23% in the untreated group at 24 h, significantly decreased following SPT treatment. At 72 h, infection rates ranged from approximately 4-7% in the SPT-treated groups. SPT significantly reduced intracellular oxidative stress by lowering reactive oxygen species levels to 17-29% relative fluorescence intensity compared with untreated infected cells, while simultaneously increasing intracellular glutathione levels. Gene expression analysis demonstrated modulation of inflammatory mediators, including upregulation of IL-12B at 100 & micro;M and TNF-alpha at 200 & micro;M, along with downregulation of IL-10, indicating a shift towards a pro-inflammatory host-protective response. Together, these findings provide in vitro evidence that SPT reduces L. infantum infection and modulates redox and inflammatory responses in C8-S astrocytes. To our knowledge, this is the first study to investigate the antileishmanial and immunomodulatory effects of SPT in an in vitro model of L. infantum-infected astrocytes.