Avaliação in vitro dos efeitos leishmanicida e imunomoduladores contra Leishmania infantum de lectinas isoladas de algas marinhas do litoral cearense

Abstract

Leishmaniasis, an infectious parasitic disease caused by protozoa of the genus Leishmania, is transmitted through the bite of infected female sandflies and primarily affects the mononuclear phagocytic system. Among its forms, visceral leishmaniasis (VL) is the most severe due to its high lethality. In Brazil, the drugs used for VL treatment include pentavalent antimonials and amphotericin B, which are associated with high toxicity and the emergence of resistant strains. Therefore, the search for new therapeutic agents is of great importance. This study aimed to investigate the immunomodulatory and leishmanicidal effects in vitro of lectins extracted from the red marine alga Solieria filiformis (Kützing) P.W. Gabrielson and the green alga Caulerpa cupressoides var. lycopodium against Leishmania infantum. After extraction and isolation of the lectins, cytotoxicity was evaluated in J774 macrophages. Subsequently, the leishmanicidal effect against the amastigote form of the parasite was assessed (24 and 48 hours post-infection) using concentrations of 5, 10, 25, 50, and 100 µg/mL. To understand the leishmanicidal mechanism of action, levels of nitric oxide (NO) and the pro- and anti-inflammatory cytokines IL-4, IL-6, IL-10, IL-12, and TNF-α were measured. The study also investigated the leishmanicidal effect of Solieria filiformis and Caulerpa cupressoides on promastigote forms. These proteins demonstrated significant leishmanicidal activity, reducing promastigote survival at different concentrations. LSf showed greater efficacy, with a reduction of up to 75.60% at 48 hours, while LCc achieved 55.68%. Regarding the leishmanicidal effect of LSf and LCc on amastigote forms in macrophages infected with L. infantum, LSf reduced the parasitic load more effectively than the positive control (GLU) at 24 and 48 hours, particularly at 100 μg/mL. NO production increased with LSf, especially at higher concentrations, while LCc induced a less pronounced increase in NO. As for cytokines, LSf elevated IL-12 and TNF-α only at specific concentrations and time points, whereas LCc significantly increased IL-10, indicating an anti-inflammatory effect. Both proteins induced IL-6 production in infected macrophages, with a more pronounced effect at 50 and 100 μg/mL. The data from this study suggest a promising immunomodulatory effect of lectins from red and green marine algae on L. infantum-infected macrophages, although further studies are needed to better elucidate the mechanisms of action of these compounds against this parasite..