title: Auranofin-induced oxidative stress causes redistribution of the glutathione pool in Taenia crassiceps cysticerci.
abstract: Previously, we have studied the effect of the gold-compound auranofin (AF) on both thioredoxin-glutathione reductasa (TGR) activity and viability of Taenia crassiceps cysticerci. It was demonstrated that micromolar concentrations of AF were high enough to fully inhibit TGR and kill the parasites. In this work, the dynamics of changes in the glutathione pool of T. crassiceps cysticerci following the addition of AF, was analyzed. A dose-dependent decrease in the internal glutathione concentration, concomitant with an increase in ROS production was observed. These changes were simultaneous with the formation of glutathione-protein complexes and the export of glutathione disulfide (GSSG) to the culture medium. Incubation of cysticerci in the presence of both AF and N-acetyl cysteine (NAC) prevents all the above changes, maintaining cysticerci viability. By contrast, the presence of both AF and buthionine sulfoximine (BSO) resulted in a potentiation of the effects of the gold compound, jeopardizing cysticerci viability. These results suggest the lethal effect of AF on T. crassiceps cysticerci, observed at micromolar concentrations, can be explained as a consequence of major changes in the glutathione status, which results in a significant increase in the oxidative stress of the parasites.
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, 04510 Mexico, DF, Mexico.
authors.forename: J J
authors.initials: JJ
authors.lastname: Martínez-González
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, 04510 Mexico, DF, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Guevara-Flores
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, 04510 Mexico, DF, Mexico.
authors.forename: J L
authors.initials: JL
authors.lastname: Rendón
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, 04510 Mexico, DF, Mexico. Electronic address: darenal@bq.unam.mx.
authors.forename: I P Del
authors.initials: IPD
authors.lastname: Arenal
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001310:Auranofin / Q000633:toxicity*; D019328:Buthionine Sulfoximine / Q000378:metabolism; D003552:Cysticercus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000032:analysis*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis; D016019:Survival Analysis; D013621:Taenia / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology
chemical_list: D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D001310:Auranofin; D019328:Buthionine Sulfoximine; D005978:Glutathione; D000111:Acetylcysteine
keywords: Auranofin; Buthionine sulfoximine; Glutathione; N-acetyl cysteine; Platyhelminths; Taenia crassiceps; Thioredoxin-glutathione reductase