NITRO RADICAL-ANION FORMATION FROM NIFURTIMOX .1. BIOLOGICAL EVIDENCES IN TRYPANOSOMA-CRUZI

Nifurtimox is a drug used against Chagas' disease. Its biotransformati on in intact epimastigotes, microsomal membranes and cytosolic fractio ns of Trypanosoma cruzi Tulahuen strain was examined. Nifurtimox reduc tion by intact cells occurred at a rate of 23.19 nmol mg protein(-1) h (-1). The nitroreductase activity was found to be distributed among th e microsomal and cytosolic fractions, being mostly NADPH dependent. Al so, in the present paper intact cells and membrane-enriched fraction o f T. cruzi were used to prove radical species formation. Results from these experiments show that the increase of the NADH-oxygen consumptio n induced by the drug, was not dependent on the respiratory chain of t he parasite. On the other hand, the nifurtimox-induced H2O2 production was significant, providing an indirect proof of the nitro radical ani on formation. (C) 1997 Elsevier Science S.A.