Effect of Isolated Proteins from Crotalus durissus terrificus Venom on Leishmania (Leishmania) Amazonensis-Infected Macrophages

Background: Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis. Methods: The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-beta from the treated macrophages were studied. Results and Discussion: Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65 +/- 0.52 mu g/mL), while convulxcin showed the weakest inhibitory effect (IC50: 52.7 +/- 2.21 mu g/mL). In addition, TGF-beta was significantly reduced after the treatment with all toxins evaluated. Conclusion: The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.