Abstract
Background: Dermaseptin-01 (DRS-01) is an antimicrobial peptide isolated from the skin secretions of frogs from Phyllomedusa genus with potential antileishmania properties. Considering that the innate immunological mechanisms underlying the production of reactive oxygen and nitrogen species is essential in controlling infection by microorganisms, the effects of DRS-01 on the immune response still remain unknown.
Methods: The effects of DRS-01 (1.0 - 256 µg mL-1) against promastigote forms of Leishmania amazonensis were evaluated, and then the IC50 value was obtained. The cytotoxicity assessment of DRS-01 by MTT assay, as well as the possible role of immunomodulatory mechanisms (phagocytic capability, and production of nitrite and hydrogen peroxide) were investigated on BALB/c peritoneal macrophages. Results: DRS-01 induced a concentration-dependent leishmanicidal effect at all times of incubation (24, 48 or 72 h). Besides, the 50% of cell viability was decreased at 32 to 128 µg mL-1 in macrophages incubated during 24 h in the MTT assay. The evaluation of immunomodulatory mechanisms demonstrates that DRS-01 (1.0 - 16 µg mL-1) increased the phagocytic capacity and the production of hydrogen peroxide, besides the decrease in the production of nitrite (8 or 16 µg mL-1). Conclusion: DRS-01 is a leishmanicidal compound acting as a modulator of the innate immunity of macrophages from BALB/c mice, reinforcing further studies concerning its potential biomedical applications in the treatment of leishmaniasis.Keywords: Antileishmanial, hydrogen peroxide, innate immunity, Leishmania, nitrite, phagocytosis, Phyllomedusa.
Graphical Abstract
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