title: Free radical metabolites in the mode of action of chemotherapeutic agents and phagocytic cells on Trypanosoma cruzi.
abstract: There are a number of biologic oxidations in Trypanosoma cruzi that generate O2- and/or H2O2. In addition, intracellular reduction followed by autoxidation yielding O2- and H2O2 has been suggested as the mode of action of several trypanocidal agents active both in vitro (e.g., naphthoquinones) and in vivo (nifurtimox) and as the basis of nifurtimox toxicity in mammals. Moreover, oxygen-reduction products have been implicated in the mechanism of killing of T. cruzi by phagocytic cells; this suggests an important role for this mechanism in host resistance and/or pathogenesis of Chagas' disease. T. cruzi possesses superoxide dismutases but lacks catalase and is partially deficient in peroxidases. This deficiency has been correlated with its sensitivity to both intracellular generators of oxygen-reduction intermediates and cell-derived oxygen metabolites. In addition, free radical intermediates apparently not related to oxygen-reduction products have also been found in the metabolic pathways of other trypanocidal drugs (benznidazole and crystal violet) used clinically in the treatment or prevention of Chagas' disease.
mesh_terms: D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014344:Trypanocidal Agents / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005609:Free Radicals; D009574:Nitro Compounds; D011809:Quinones; D014344:Trypanocidal Agents; D013481:Superoxides; D006861:Hydrogen Peroxide