The reductive metabolism of nifurtimox and benznidazole in Crithidia fasciculata is similar to that in Trypanosoma cruzi.
1. Addition of nifurtimox or benznidazole to the NADH-containing mitochondrial fraction of Crithidia fasciculata led to the appearance of the characteristic ESR spectra corresponding to their nitro anion radicals, suggesting that the nitro anion radical is a necessary intermediate in the reduction of both nitro compounds. 2. Nifurtimox anion radical generation by the mitochondrial fraction was insensitive to rotenone and antimycin A but was enhanced by KCN. 3. The nifurtimox anion radical reacted with oxygen under aerobic conditions leading to an increase in the cyanide-insensitive respiration of the intact cells and in the rate of O2- and H2O2 production by the C. fasciculata mitochondrial fraction. 4. In contrast, generation of O2- and H2O2 was not stimulated with pharmacological concentrations of benznidazole. Furthermore, benznidazole inhibited the cyanide-insensitive respiration of the intact cells.
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Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Cidade Universitária, Brazil.
D000818:Animals; D003421:Crithidia / Q000378:metabolism*; D005609:Free Radicals; D008928:Mitochondria / Q000378:metabolism; D009547:Nifurtimox / Q000378:metabolism*; D009581:Nitrofurans / Q000378:metabolism*; D009593:Nitroimidazoles / Q000378:metabolism*; D010084:Oxidation-Reduction; D014344:Trypanocidal Agents / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000378:metabolism*
D005609:Free Radicals; D009581:Nitrofurans; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009547:Nifurtimox; C009999:benzonidazole