Trypanosoma cruzi dihydrolipoamide dehydrogenase as target of reactive metabolites generated by cytochrome c/hydrogen peroxide (or linoleic acid hydroperoxide)/phenol systems.

This study determines that cytochrome c (cyt c) catalyses the oxidation of phenol compounds (Phen) in the presence of H2O2 or linoleic acid hydroperoxide (LOOH), generating Phen-derived free radicals or other reactive metabolites. These products irreversibly inactivated the dihydrolipoamide dehydrogenase from Trypanosoma cruzi (T cruzi LADH), depending on: the Phen structure, peroxide type, activated cyt c, incubation time and presence of an antioxidant. Nordihydroguaiaretic acid (NDGA) and caffeic acid (CAFF) with cyt c/H2O2 or cyt c/LOOH were the most effective inhibitors of T cruzi LADH.

Trypanosoma cruzi dihydrolipoamide dehydrogenase as target for phenothiazine cationic radicals. Effect of antioxidants.

Myeloperoxidase (MPO), myoglobin (Mb) and horseradish peroxidase (HRP), catalyzed the generation of radical-cations by one-electron oxidation of phenothiazines (PTZ). The transient formation of these radicals (PTZ+.) was confirmed by ESR and optical spectroscopy.

Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers.

Phenothiazine cation radicals (PTZ+*) irreversibly inactivated Trypanosoma cruzi dihydrolipoamide dehydrogenase (LADH). These radicals were obtained by phenothiazine (PTZ) peroxidation with myeloperoxidase (MPO) or horseradish peroxidase (HRP/H2O2) systems. LADH inactivation depended on PTZ structure and incubation time.