Avaliação do efeito do composto 4-nitrobenzoilcumarínico em camundongos experimentalmente infectados por Trypanosoma cruzi

Abstract

Previous studies have shown that coumarin compounds exhibit anticancer and antiparasitic activities and have recently demonstrated important in vitro activity of the 4-nitrobenzoylcoumarin compound (4NBC) specifically against Trypanosoma cruzi. Here, we evaluated the trypanocidal effect of 4NBC alone and in combination with benznidazole (Bz) using fifty-five Swiss mice experimentally infected with T. cruzi Y strain, divided into 8 groups. Cure rates were checked by microscopic examination of fresh blood, as well as blood culture and real time PCR. Cardiac inflammation of treated animals was checked after euthanasia compared to uninfected group and infected and untreated mice in tissue sections stained with hematoxylin & eosin. Treatment toxicity assessments were performed considering (i) weekly animal weights, (ii) dosages of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) liver injury markers, and (iii) histopathological analyzes of liver tissues. The involvement of humoral immune response in experimental therapy was investigated by assessing the levels of G immunoglobulins class (IgG) and their IgG1, IgG2a and IgG2b isotypes. All therapeutic regimens were effective in preventing the death of 100% of the animals. Overall, the treatments were well tolerated, as evidenced by monitoring of animal weights, AST and ALT enzymes measurements and analysis of the hepatic tissue. The benefit of using coumarin alone or in combination was evidenced by the reduction of the area under the parasitaemia curve in relation to infected and untreated animals. Parasitological cure was observed only between the animals treated with Bz in monotherapy and in the combination of 100mg/kg of 4NBC with 50mg/kg of Bz. All combinations of Bz with 4NBC showed to be more effective in preventing myocarditis and reducing the production of imunoglobulins compared to the group treated with 50mg/kg of Bz. The results show that compound 4NBC has trypanocidal activity, which is well tolerated by the host and that it can positively interfere in the prevention of typical myocarditis of Chagas disease.