Res Commun Mol Pathol Pharmacol
Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, Pcia. de Buenos Aires, Argentina.
Published: December 1997
Nifurtimox (Nfx) 4-[(5-nitrofurfurylidine)amino-3-methylthiomorpholine-1-1-di oxide] is a drug that is being used to treat American Trypanosomiasis (Chagas' disease). Nfx has serious toxic effects including mutagenic, reproductive and carcinogenic actions. Its toxicity has been linked to NADPH dependent nitroreductive metabolic biotransformation with production of oxygen reactive species. In this study is reported that rat liver nuclei exhibit Nfx-nitroreductase activity (Nfx-ase). This activity is null under oxygen and partially inhibited under CO. Nfx does not promote a lipid peroxidation process. Results suggest that Nfx is biotransformed partially at a cytochrome P450 level but mostly by NADPH P450 reductase. Formation of reactive metabolites nearby DNA and nuclear proteins might be related to long term deleterious effects of this drug.
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