title: Trypanosoma cruzi dihydrolipoamide dehydrogenase as target of reactive metabolites generated by cytochrome c/hydrogen peroxide (or linoleic acid hydroperoxide)/phenol systems.
abstract: 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. The comparison of inactivation values for T cruzi and mammalian heart enzymes demonstrated a greater sensitivity of T cruzi LADH to Phen. GSH, N-acetylcysteine, NAD(P)H, ascorbate and trolox, prevented T cruzi LADH inactivation by acetaminophen. The role of the Phen as potential trypanocidal systems is discussed.
authors.affiliation: Instituto de Medicina Tropical Daniel A Carrión, Universidad Nacional Mayor de San Marcos, Lima, Perú. josegutierrezc2@yahoo.es
authors.forename: José
authors.initials: J
authors.lastname: Gutiérrez-Correa
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019787:Linoleic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015800:Protozoan Proteins / Q000378:metabolism*; D013552:Swine; D014349:Trypanosoma cruzi / Q000378:metabolism*
chemical_list: D016877:Oxidants; D010636:Phenols; D015800:Protozoan Proteins; D045304:Cytochromes c; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; D008058:Dihydrolipoamide Dehydrogenase