info:eu-repo/semantics/article
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems
Fecha
2002-11Registro en:
Montalto, Maria; Diaz, Edith Graciela; Castro, Jose Alberto; Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems; Elsevier Ireland; Toxicology Letters; 136; 1; 11-2002; 1-8
0378-4274
CONICET Digital
CONICET
Autor
Montalto, Maria
Diaz, Edith Graciela
Castro, Jose Alberto
Resumen
Liver microsomal (mic); nuclei (N) and mitochondria (mit) anaerobically nitroreduce Nifurtimox (Nfx) in the presence of NADPH generating system. Simultaneous formation of small amounts of nitrite was observed in microsomes and nuclei but not in mitochondria. The microsomal nitroreductase activity was enhanced by the presence of flavine-adenine-dinucleotide disodium salt (FAD), was not inhibited by CO and was significantly inhibited by diphenyleneiodonium (DPI). In the microsomal NADPH-dependent fraction nitrite formation was null in the presence of FAD, DPI and under air and was partially inhibited by pure CO. Pure human cytochrome P450 reductase in the presence of NADPH significantly nitroreduced Nfx and produced small amounts of nitrite. The nitroreductive process was significantly enhanced by FAD but the nitrite formation became null. FAD itself was able to chemically nitroreduce Nfx without production of nitrite. NADPH generating system enhanced the FAD nitroreductive effect and led to small production of nitrite. Formation of reactive metabolites and nitric oxide during Nfx metabolism might contribute to its toxicity.