Effect of nitroheterocyclic drugs on lipid peroxidation and glutathione content in rat liver extracts.

Incubation of rat liver cell-free extracts with an NADPH-generating system and with nifurtimox or benznidazole (two nitroheterocyclic drugs used in the treatment of Chagas' disease) produced oxidation of reduced glutathione (GSH) and increased lipid peroxidation, as shown by the generation of thiobarbituric-acid-reacting intermediates. Nifurtimox and benznidazole inhibited GSSG-reductase, but not GSH-peroxidase, the former inhibition contributing to GSH depletion. In every case, nifurtimox was more effective than benznidazole. Addition of GSH or free-radical scavengers (catalase, superoxide dismutase, mannitol, sodium benzoate or L-histidine) prevented the effect of nifurtimox on lipid peroxidation reactions. These results support the assumption [M. Dubin, S. N. J. Moreno, E. E. Martino, R. Docampo and A. O. M. Dubin, Biochem. Pharmac. 32, 483 (1983)] that, in the rat liver, GSH exerts a protective action against oxygen radicals generated by the nitroheterocyclic drugs.