Avaliação pré-clínica da combinação de benznidazol e curcumina no tratamento etiológico da infecção por T. cruzi

Abstract

The American trypanosomiasis or Chagas disease is a neglected tropical disease caused by protozoan parasite Trypanosoma cruzi. Chagas' disease is the leading cause of non-ischemic cardiomyopathy worldwide. Although chemotherapy with benznidazol is recommended as a reference in the etiological treatment of the disease, after the parasite settling in multiple organs of the vertebrate host, healing is usually not achieved. Thus, new drugs and therapeutic schedules have been tested in the search for more tolerable and effective strategies for the treatment of disease. Due to its anti-inflammatory activity, antioxidant and immunomodulatory, the currumina has shown promising effects on the treatment of parasitic diseases such as malaria, leishmaniasis and schistosomiasis. However, the applicability of curcumin in the therapeutic management of Chagas disease is still unknown. Thus, the present study was designed to investigate the influence of treatment with benznidazol and curcumin on blood and cardiac parasitism, inflammatory response, oxidative damage and morphological myocardial remodeling in mice infected with T. cruzi. Eighty-four Swiss female mice eight weeks of life were equally divided into seven groups: G1, uninfected; G2, infected; G3 infected benznidazol + (100 mg / kg); G4 infected benznidazol + (50 mg / kg); G5, infected + curcumin (100mg / kg); G6 infected benznidazol + (100 mg / kg) + curcumin (100mg / kg); G7 infected benznidazol + (50 mg / kg) + curcumin (100mg / kg). The infected animals were inoculated intraperitoneally with 2000 trypomastigotes of T. cruzi Y strain. The benznidazol and curcumin were administered orally once daily for 20 days by gavage. The results showed that curcumin had limited antiparasitic effects, but when combined with benznidazol, this molecule enhanced the therapeutic action of the reference chemotherapy. Apparently, this effect was mediated by a greater reduction in parasitemia, parasite load, inflammation and cardiac oxidative damage and block the reactivation of the infection after completion of treatment. In addition to increasing the survival and cure rate in infected mice, the combined treatment also attenuated hepatic toxicity induced by benznidazol, preventing reactivation of infection even when the animals were treated with half the therapeutic dose recommended for benznidazol.