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

DF

Congreso; 13th International Congress of Parasitology - ICOPA XIII; 2014

BACKGROUND: Chagas disease (CD) treatment is controversial due to partialeffectiveness, physicochemical problems and side effects of currently used drugs. Forthis, we evaluated the effect of Clomipramine (CLO), an inhibitor of T. cruzitrypanothione reductase, as an alternative therapy. T. cruzi invasion and replicationproduce reactive oxygen species that target mitochondria, modifying the energy supplyand impacting in the genesis and progression of the cardiopathy. Additionally, clinicalvariability could also be explained by parasite genetic heterogeneity.METHODS: Albino Swiss mice were infected with 50 parasites of an isolate from anendemic area in Argentina (SGO-Z12). It was characterized using two typing methods.Treatments were performed in the acute and chronic phases. For both moments, micewere divided into (n=20 in each group): not-infected (NI), infected non-treated andinfected and treated with CLO (5mg/kg/day). Acute phase: CLO was administered for30 days. Chronic phase, electrocardiographic abnormalities were criteria to begintreatment: CLO was administered for 60 days. Treatment effectiveness was measuredby survival, parasitemia and qPCR. Mitochondrial function in myocardium and skeletalmuscle was studied by determining the activity of complexes II and III (CII-CIII) of therespiratory chain.RESULTS: SGO-Z12 isolate consisted of a mixture of lineages II and VI. Bothtreatments were effective in reducing parasitemia (qPCR), increasing survival andreestablishing skeletal muscle CII activity to NI values. CIII activity however, remainedaltered.CONCLUSIONS: The diminished parasitemia in the treated groups probably improvedtheir mitochondrial function, preserving the cardiac activity and therefore allowing ahigher survival than non-treated groups.