Response of a Trypanosoma cruzi isolate to clomipramine treatment in the acute and chronic phases and the effects upon mitochondrial activity

STRAUSS MARIANA; BAZÁN CAROLINA; BÁEZ ALEJANDRA; MOYA DIEGO; ESTEVES BLANCA; MILER NOEMÍ; LO PRESTI SILVINA; PAGLINI PATRICIA; RIVAROLA WALTER

Ciudad de México

Congreso; 13th International Congress of Parasitology ? ICOPA XIII.; 2014

BACKGROUND: Chagas disease (CD) treatment is controversial due to partial effectiveness, physicochemical problems and side effects of currently used drugs. For this, we evaluated the effect of Clomipramine (CLO), an inhibitor of T. cruzi trypanothione reductase, as an alternative therapy. T. cruzi invasion and replication produce reactive oxygen species that target mitochondria, modifying the energy supply and impacting in the genesis and progression of the cardiopathy. Additionally, clinical variability could also be explained by parasite genetic heterogeneity. METHODS: Albino Swiss mice were infected with 50 parasites of an isolate from an endemic area in Argentina (SGO-Z12). It was characterized using two typing methods. Treatments were performed in the acute and chronic phases. For both moments, mice were divided into (n=20 in each group): not-infected (NI), infected non-treated and infected and treated with CLO (5mg/kg/day). Acute phase: CLO was administered for 30 days. Chronic phase, electrocardiographic abnormalities were criteria to begin treatment: CLO was administered for 60 days. Treatment effectiveness was measured by survival, parasitemia and qPCR. Mitochondrial function in myocardium and skeletal muscle was studied by determining the activity of complexes II and III (CII-CIII) of the respiratory chain. RESULTS: SGO-Z12 isolate consisted of a mixture of lineages II and VI. Both treatments were effective in reducing parasitemia (qPCR), increasing survival and reestablishing skeletal muscle CII activity to NI values. CIII activity however, remained altered. CONCLUSIONS: The diminished parasitemia in the treated groups probably improved their mitochondrial function, preserving the cardiac activity and therefore allowing a higher survival than non-treated groups.