title: Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease.
abstract: Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.
authors.affiliation: Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil romuonovaes@yahoo.com.br ivocaldass@yahoo.com.br.
authors.forename: Rômulo Dias
authors.initials: RD
authors.lastname: Novaes
authors.affiliation: Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: Marcus Vinicius Pessoa
authors.initials: MV
authors.lastname: Sartini
authors.affiliation: Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: João Paulo Ferreira
authors.initials: JP
authors.lastname: Rodrigues
authors.affiliation: Department of Animal Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Reggiani Vilela
authors.initials: RV
authors.lastname: Gonçalves
authors.affiliation: School of Medicine, Federal University of Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil.
authors.forename: Eliziária Cardoso
authors.initials: EC
authors.lastname: Santos
authors.affiliation: Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
authors.forename: Raquel Lopes Martins
authors.initials: RL
authors.lastname: Souza
authors.affiliation: Department of Pathology and Parasitology, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil romuonovaes@yahoo.com.br ivocaldass@yahoo.com.br.
authors.forename: Ivo Santana
authors.initials: IS
authors.lastname: Caldas
mesh_terms: D000208:Acute Disease; D000818:Animals; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology*; D003474:Curcumin / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D008099:Liver / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D009593:Nitroimidazoles / Q000627:therapeutic use*; D018512:Parasitemia / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D000637:Transaminases / Q000097:blood; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D016207:Cytokines; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D000637:Transaminases; D003474:Curcumin; C009999:benzonidazole