PERSONAL DE APOYO
FANELLI Silvia Laura
congresos y reuniones científicas
Título:
Nifurtimox and Benznidazole metabolism in rat heart. Ultrastructural and biochemical observations
Autor/es:
BARTEL LC; MONTALTO DE MECCA M; R. DE CASTRO C; FANELLI SL; DÍAZ EG; CASTRO JA.
Lugar:
Córdoba
Reunión:
Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2006
Institución organizadora:
Sociedad Argentina de Farmacología Experimental (SAFE)
Resumen:
There are available two drugs for the ethiological treatment of  Chagas? disease, Nifurtimox (Nfx) and Benznidazole (Bz). They are being used in the acute phase and recently they were used in the indeterminate phase. Both nitroheterocyclic drugs have serious toxic side effects. The mechanism of toxicity is associated with their nitroreduction and the generation of reactive metabolites. Their potential effects on cardiac function are yet not known, in spite of the well known cardiopathy generally produced by the disease. We describe initial experiments to test the acute effects of both drugs  on rat heart. Male Sprague Dawley rats were treated ig with either Nfx or Bz. They reached the tissue at 1, 3 and 6 h after treatment. In vitro studies on Nfx and Bz microsomal and cytosolic nitroreductase activities showed that only the microsomal fraction had the ability to nitroreduce both drugs. CYP and P450 reductase would be involved as suggested by the CO, SKF 525-A and DPI inhibition. Nfx increased the protein carbonyl content at 1 and 3 h and decreased the protein sulfhydryl content at 3 h. In addition, 24 h after treatment ultrastructural alterations such as marked cytoplasm vacuolization, separation and loss of myofibrils and mitochondrial swelling were observed. Results suggest that Nfx administration might aggravate pre-existing adverse cardiac conditions. Bz effects are under study.