Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats.
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.
Pederzolli
Carolina Didonet
CD
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.
Mescka
Caroline Paula
CP
Zandoná
Bernardo Remuzzi
BR
de Moura Coelho
Daniella
D
Sgaravatti
Angela Malysz
AM
Sgarbi
Mirian Bonaldi
MB
de Souza Wyse
Angela Terezinha
AT
Duval Wannmacher
Clóvis Milton
CM
Wajner
Moacir
M
Vargas
Carmen Regla
CR
Dutra-Filho
Carlos Severo
CS
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
D000975:Antioxidants; D009419:Nerve Tissue Proteins; D005981:Glutathione Synthase; D011761:Pyrrolidonecarboxylic Acid