In vitro activity of phospholipase A2 and of peptides from Crotalus durissus terrificus venom against amastigote and promastigote forms of Leishmania (L.) infantum chagasi. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Barros, Gustavo; Pereira, Andreia; Barros, Luciana; Jr, Airton; Calvi, Sueli; Santos, Lucilene; Barraviera, Benedito; Ferreira, Rui
• Is Part Of: Journal of venomous animals and toxins including tropical diseases. Volume 21:Issue 1(2015)
• Page Start: 1
• Page End: 9
• Publication Date: 2015-12
• Subjects: PLA2 -- Peptides -- Crotalus dutissus terrificus -- Venom -- Leishmanicidal activity; Poisonous animals -- Periodicals; Venom -- Periodicals; Toxins -- Periodicals; Tropical medicine -- Periodicals; Venoms -- Periodicals; Toxins -- Periodicals; Animals, Poisonous -- Periodicals; Tropical Medicine -- Periodicals; Animals, Poisonous -- Periodicals; Venoms -- Periodicals; Tropical Medicine -- Periodicals; Toxins -- Periodicals; Poisonous animals; Tropical medicine; Venom; Periodicals; Electronic journals; 615.9405
• DOI: 10.1186/s40409-015-0049-0
• Languages: English
• ISSNs: 1678-9199

Abstract

Abstract Background American visceral leishmaniasis is caused by the intracellular parasiteLeishmania (L.) infantum chagasi, and transmitted by the sand flyLutzomyia longipalpis . Since treatment is based on classical chemotherapeutics with significant side effects, the search for new drugs remains the greatest global challenge. Thus, this in vitro study aimed to evaluate the leishmanicidal effect ofCrotalus durissus terrificus venom fractions on promastigote and amastigote forms ofLeishmania (L.) infantum chagasi . Methods Phospholipase A2 (PLA2 ) and a pool of peptide fraction (<3 kDa) were purified fromCrotalus venom. Furthermore, promastigotes and peritoneal macrophages of mice infected by amastigotes were exposed to serial dilutions of the PLA2 and peptides at intervals varying between 1.5625 μg/mL and 200 μg/mL. Both showed activity against promastigotes that varied according to the tested concentration and the time of incubation (24, 48 and 72 h). Results MTT assay for promastigotes showed IC50 of 52.07 μg/mL for PLA2 and 16.98 μg/mL for the peptide fraction of the venom. The cytotoxicity assessment in peritoneal macrophages showed IC50 of 98 μg/mL and 16.98 μg/mL for PLA2 and peptide by MTT assay, respectively. In peritoneal macrophages infected byLeishmania (L.) infantum chagasi amastigotes, the PLA2 stimulated growth of parasites, and at higher doses reduced growth by 23 %. The peptide fraction prevented 43 % of the intracellular parasite growth at a dose of 16.98 μg/mL, demonstrating the toxicity of this dose to macrophages. Both fractions stimulated H2 O2 production by macrophages but only PLA2 was able to stimulate NO production. Conclusion We have demonstrated the in vitro leishmanicidal activity of the PLA2 and peptide fraction ofCrotalus venom. The results encourage further studies to describe the metabolic pathways involved in cell death, as well as the prospecting of molecules with antiparasitic activity present in the peptide fraction ofCrotalus durissus terrificus venom.