Quimioterapia experimental: combinação do alopurinol com o benzonidazol, em camundongos infectados pela cepa Y do Trypanosoma cruzi, durante a fase aguda da doença de Chagas

Abstract

EXPERIMENTAL CHEMOTHERAPY: COMBINATION OF BENZNIDAZOLE WITH ALLOPURINOL IN MICE INFECTED BY THE Y STRAIN OF TRYPANOSOMA CRUZI DURING THE ACUTE PHASE OF CHAGAS DISEASE. Introduction: Chagas disease is a anthropozoonosis caused by the flagellate protozoan Trypanosoma cruzi . In Brazil, benznidazole is the only available drug for the specific treatment of the disease. Combining other drugs with benznidazole may be a new therapeutic strategy for Chagas disease. Objective: To evaluate the treatment effect of benznidazole associated with allopurinol over the course of infection by the Y strain of T. cruzi in swiss mice during the acute phase of Chagas disease. Methods: Experimental study using 49 swiss albino mice , not isogenic and both sexes. They were divided into 4 groups: I - control infected and untreated; II - Treated 100mg/kg/d of benznidazole; III - Treated with allopurinol 60mg/kg/day; IV - Treaties with benznidazole + allopurinol. Treatment was initiated on the 9th day post-infection and were administered 60 doses of medication. The parasitemia and mortality were monitored daily. 60 days after the end of treatment the following tests of cure were performed: xenodiagnosis, parasitemia, blood culture, indirect immunofluorescence and histopathological analysis of heart and skeletal muscle. Results: There was 100% mortality of mice in groups I and III, 5.26% in the IV group and 0% in group II. Tests of cure showed parasitological cure in 100% of camungondos in groups II and IV and serological cure in 60% of group II and group IV 100%. The histopathological analysis showed lower degree of tissue injury in mice treated with the combination of drugs. Discussion: Although the allopurinol monotherapy is not effective for parasite control of Chagas disease in the acute phase, its association with benznidazole may be important to increase the cure rate and decrease the tissue damage found in heart and skeletal muscle in chronic phase disease. Conclusion: The results of treatment of benznidazole associated with allopurinol showed the curative efficacy of combined chemotherapy and sharp decrease in lesions in cardiac and skeletal muscle.