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Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response


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Background: Apis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases. Methods: Africanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H2O2 by macrophages was determined. Results: Promastigotes and intracellular amastigotes were susceptible to melittin (IC50 28.3 μg.mL-1 and 1.4 μg.mL-1, respectively), but also showed mammalian cell cytotoxicity with an IC50 value of 5.7 μg.mL-1. Uninfected macrophages treated with melittin increased the production of IL-10, TNF-aα, NO and H2O2. Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-aα, NO and H2O2. Conclusions: The results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect.

São Paulo State University (UNESP - Univ Estadual Paulista) Graduate Program in Tropical Diseases Botucatu Medical School

Adolfo Lutz Institute Department of Parasitology

University of São Paulo (USP) Laboratory of Protozoology Institute for Tropical Medicine

São Paulo State University (UNESP - Univ Estadual Paulista) Department of Animal Production School of Veterinary Medicine and Animal Husbandry

São Paulo State University (UNESP - Univ Estadual Paulista) Center for the Study of Venoms and Venomous Animals (CEVAP), Rua José Barbosa de Barros, 1780

Butantan Institute Laboratory of Biochemistry and Biophysics

São Paulo State University (UNESP - Univ Estadual Paulista) Graduate Program in Tropical Diseases Botucatu Medical School

São Paulo State University (UNESP - Univ Estadual Paulista) Department of Animal Production School of Veterinary Medicine and Animal Husbandry

São Paulo State University (UNESP - Univ Estadual Paulista) Center for the Study of Venoms and Venomous Animals (CEVAP), Rua José Barbosa de Barros, 1780

Tipo de Documento Artigo científico
Idioma Inglês
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