ABSTRACT
We investigated the immunomodulatory, antiparasitic and cardioprotective effects of a sesquiterpene lactone (SL) administered alone or combined with benznidazole (Bz), in a murine model of Chagas' disease by in vitro and in vivo assays. Antiparasitic and cytotoxic potential of tagitinin C (SL) and Bz were tested in vitro against T. cruzi epimastigotes and cardiomyocytes. Swiss mice challenged with T. cruzi were also treated for 20â¯days with tagitinin C (10â¯mg/kg) alone and combined with Bz (100â¯mg/kg). Tagitinin C exhibited a higher antiparasitic (IC50: 1.15⯵M) and cytotoxic (CC50 at 6.54⯵M) potential than Bz (IC50: 35.81⯵M and CC50: 713.5⯵M, respectively). When combined, these drugs presented an addictive interaction, determining complete suppression of parasitemia and parasitological cure in all infected mice (100%) compared to those receiving Bz alone (70%). Anti-T. cruzi immunoglobulin G, and pro-inflammatory cytokines IFN-γ and TNF-α levels were reduced in animals treated with tagitinin C combined with Bz, while IL-10 production was unaffected. Heart inflammation was undetectable in 90% of the animals receiving this combination, while only 50% of the animals receiving Bz alone showed no evidence of myocarditis. Together, our findings indicated that the combination of tagitinin C and Bz exerts potent antiparasitic, immunomodulatory and cardioprotective effects. Due to the remarkable suppression of parasitemia and high parasitological cure, this combination was superior to Bz monotherapy, indicating a high potential for the treatment of Chagas's disease.