Tityus serrulatus scorpion venom as a potential drug source for Chagas' disease: Trypanocidal and immunomodulatory activity

Current chemical therapies for Chagas Disease (CD) lack ability to clear Trypanosoma cruzi (Tc) parasites and cause severe side effects, making search for new strategies extremely necessary. We evaluated the action of Tityus serrulatus venom (TsV) components during Tc infection. TsV treatment increased nitric oxide and pro-inflammatory cytokine production by Tc-infected macrophages (MØ), decreased intracellular parasite replication and trypomastigotes release, also triggering ERK1/2, JNK1/2 and p38 activation. Ts7 demonstrated the highest anti-Tc activity, inducing high levels of TNF and IL-6 in infected MØ. TsV/Ts7 presented synergistic effect on p38 activation when incubated with Tc antigen. KPP-treatment of MØ also decreased trypomastigotes releasing, partially due to p38 activation. TsV/Ts7-pre-incubation of Tc demonstrated a direct effect on parasite decreasing MØ-trypomastigotes releasing. In vivo KPP-treatment of Tc-infected mice resulted in decreased parasitemia. Summarizing, this study opens perspectives for new bioactive molecules as CD-therapeutic treatment, demonstrating the TsV/Ts7/KPP-trypanocidal and immunomodulatory activity during Tc infection. [Display omitted] •TsV induces inflammatory mediators inhibiting T. cruzi replication in host cells.•TsV components have a direct effect in T. cruzi differentiation.•The mechanism of TsV-trypanocidal activity involve MAPKs signaling in host cells.•Ts14-derived tripeptide (KPP) retain the trypanocidal activity in vitro and in vivo.•KPP a potential candidate to design drugs for Chagas disease treatment.