Recently it has become increasingly apparent that many reactive intermediates of xenobiotics are free radicals. The formation of free radicals, including oxygen-derived radicals, may lead to extensive cellular damage. The consequences of radical-initiated reactions may be the immediate death of the cells or may be more subtle and delayed as evidenced by the development of neoplasms. In a study of Trypanosoma cruzi (the agent of Chagas' disease), crystal violet, a triarylmethane dye widely used by blood banks to eliminate transmission of Chagas' disease by transfusion, was found to undergo a one-electron reduction to produce a carbon-centered free radical. Both radical formation and the trypanocidal action of crystal violet were enhanced by light. The photodynamic action of gentian violet in blood was apparently mediated by ascorbic acid oxidation. In addition, we demonstrated that photolysis of gentian violet in aqueous medium saturated with O2 does not generate singlet oxygen. The photodynamic action of rose bengal on T. cruzi has also been established. These observations may have important chemoprophylactic implications, since illumination of blood to be transfused may result in a better therapeutic ratio. We provided evidence for the one-electron reduction of benznidazole by T. cruzi homogenates and described differences between nifurtimox and benznidazole modes of action on T. cruzi. In addition, we provided evidence for the involvement of O2 radicals in the killing of T. cruzi by polymorphonuclear leukocytes. Finally the ability of Tritrichomonas foetus (the agent of trichomoniasis in cattle) hydrogenosomal and cytosolic fractions to generate nitroimidazole and nitrofuran anion radicals was established. These results support the role of air oxidation as a detoxification reaction for the nitroimidazoles anion radicals and the involvement of a ferredoxin in their formation. On the other hand, redox cycling of nitrofurans, with formation of high steady state concentrations of oxygen-derived radicals, might be of toxicological significance.
