PERSONAL DE APOYO
FANELLI Silvia Laura
congresos y reuniones científicas
Título:
Nifurtimox nitroreductase activity in the cellular fractions from male rat pancreas
Autor/es:
MONTALTO DE MECCA M., FANELLI S.L., BARTEL L.C., DÍAZ E.G. Y CASTRO J.A.
Lugar:
Iguazú, Misiones
Reunión:
Congreso; IL Annual Meeting Sociedad Argentina de Investigación en bioquímica y Biología Molecular (SAIB),; 2004
Institución organizadora:
Sociedad Argentina de Investigación en bioquímica y Biología Molecular (SAIB)
Resumen:
Nifurtimox (Nfx) is a drug used in the treatment of Chagas? disease. It has shown toxic side effects believed to be related to its nitroreduction. The aim of this study was to analyze the ability of Sprague Dawley male rat pancreas cellular fractions to nitroreduce Nfx and to provoke some deleterious effects. Microsomes exhibited Nfx nitroreductase activity in the presence of NADPH and under N2 atmosphere (0.493 ± 0.016 pmol/min. mg prot) that was fully inhibited under air but not altered when N2 was replaced by pure CO. The mitochondrial fraction was not able to nitroreduce Nfx in the presence of NADPH. The cytosol nitroreduced Nfx in the presence of hipoxantine and under N2 (0.212 ± 0.049 pmol/min.mg prot), that was negligible under air and inhibited by allopurinol. Nfx levels in pancreatic tissue, at 1, 3 or 6 h after intragastric administration (100 mg/kg) were 4,01 ± 3.41; 5,95 ± 2.18; 2,63 ± 1.03 mg/g respectively. A significant increase in t-buthylhidroperoxide promoted chemioluminicence was detected after 6 h Nfx. Protein sulfhydryl content significantly decreased at either 1, 3 or 6 h after Nfx administration. Results evidence that Nfx reaches the pancreas and that might be nitroreduced there, to produce some deleterious effects which still remain to be fully determined. Supported by FONCyT (PICT/00-5-9941) and UNSAM (PIDAUF014)