title: Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats.
abstract: 5-Oxoproline accumulates in glutathione synthetase deficiency, an autossomic recessive inherited disorder clinically characterized by hemolytic anemia, metabolic acidosis, and severe neurological symptoms whose mechanisms are poorly known. In the present study we investigated the effects of acute subcutaneous administration of 5-oxoproline to verify whether oxidative stress is elicited by this metabolite in vivo in cerebral cortex and cerebellum of 14-day-old rats. Our results showed that the acute administration of 5-oxoproline is able to promote both lipid and protein oxidation, to impair brain antioxidant defenses, to alter SH/SS ratio and to enhance hydrogen peroxide content, thus promoting oxidative stress in vivo, a mechanism that may be involved in the neuropathology of gluthatione synthetase deficiency.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.
authors.forename: Carolina Didonet
authors.initials: CD
authors.lastname: Pederzolli
authors.forename: Caroline Paula
authors.initials: CP
authors.lastname: Mescka
authors.forename: Bernardo Remuzzi
authors.initials: BR
authors.lastname: Zandoná
authors.forename: Daniella
authors.initials: D
authors.lastname: de Moura Coelho
authors.forename: Angela Malysz
authors.initials: AM
authors.lastname: Sgaravatti
authors.forename: Mirian Bonaldi
authors.initials: MB
authors.lastname: Sgarbi
authors.forename: Angela Terezinha
authors.initials: AT
authors.lastname: de Souza Wyse
authors.forename: Clóvis Milton
authors.initials: CM
authors.lastname: Duval Wannmacher
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000502:physiology; D020739:Brain Diseases, Metabolic, Inborn / Q000139:chemically induced* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D054022:Cerebrum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005981:Glutathione Synthase / Q000172:deficiency; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D009419:Nerve Tissue Proteins; D005981:Glutathione Synthase; D011761:Pyrrolidonecarboxylic Acid