title: Pro-oxidant action of diphenyl diselenide in the yeast Saccharomyces cerevisiae exposed to ROS-generating conditions.
abstract: Organoselenium compounds have a potential thiol peroxidase-like activity. Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. Using TRAP assay of chemiluminescense we have shown that diphenyl diselenide clearly possesses a pro-oxidant property. For an investigation on the mechanisms of this property, we used mutant strains of Saccharomyces cerevisiae defective in antioxidant defenses, i.e. in superoxide dismutase, in biosynthesis of glutathione, and the transcription factor yAP-1-lacking yap 1 mutant that cannot activate genes of the oxidative stress response. Exposure of growing cultures to the drug increased cell sensitivity to oxidizing agents. The pro-oxidant effect was independent of the metabolic condition or of the oxidative mutagen tested. N-acetylcysteine, a precursor of glutathione biosynthesis, could neutralize the pro-oxidant effects of diphenyl diselenide by stimulating an increase of endogenous glutathione biosynthesis or by directly binding to the drug. Vitamin E (Trolox), a known antioxidant, was also able to protect S. cerevisiae against the pro-oxidant effect of diphenyl diselenide. In vitro assays showed that diphenyl diselenide interacts non-enzymatically with the thiol group of glutathione.
authors.affiliation: Centro de Biotecnologia/Departamento de Biofísica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil.
authors.forename: Renato
authors.initials: R
authors.lastname: Moreira Rosa
authors.forename: Ramatis Birnfeld
authors.initials: RB
authors.lastname: de Oliveira
authors.forename: Jenifer
authors.initials: J
authors.lastname: Saffi
authors.forename: Antônio Luís
authors.initials: AL
authors.lastname: Braga
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: José Cláudio
authors.initials: JC
authors.lastname: Fonseca Moreira
authors.forename: Martin
authors.initials: M
authors.lastname: Brendel
authors.forename: João Antonio
authors.initials: JA
authors.lastname: Pêgas Henriques
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001555:Benzene Derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001761:Bleomycin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D005285:Fermentation; D016166:Free Radical Scavengers / Q000494:pharmacology; D005800:Genes, Fungal / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry; D009154:Mutation / Q000502:physiology; D016566:Organoselenium Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D001555:Benzene Derivatives; D016166:Free Radical Scavengers; D016566:Organoselenium Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D001761:Bleomycin; D014810:Vitamin E; C061132:diphenyldiselenide; D008165:Luminol; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen