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 su...

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Published in:Metabolic brain disease 2010-06, Vol.25 (2), p.145-154
Main Authors: Pederzolli, Carolina Didonet, Mescka, Caroline Paula, Zandoná, Bernardo Remuzzi, de Moura Coelho, Daniella, Sgaravatti, Ângela Malysz, Sgarbi, Mirian Bonaldi, de Souza Wyse, Angela Terezinha, Duval Wannmacher, Clóvis Milton, Wajner, Moacir, Vargas, Carmen Regla, Dutra-Filho, Carlos Severo
Format: Article
Language:English
Subjects:
5-Oxoproline
Age Factors
Animals
Antioxidant defenses
Antioxidants - metabolism
Antioxidants - physiology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Brain Diseases, Metabolic, Inborn - chemically induced
Brain Diseases, Metabolic, Inborn - metabolism
Cerebellum - drug effects
Cerebellum - metabolism
Cerebrum - drug effects
Cerebrum - metabolism
Disease Models, Animal
Glutathione Synthase - deficiency
Glutathione synthetase deficiency
Lipid Peroxidation - drug effects
Lipid Peroxidation - physiology
Metabolic Diseases
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - physiology
Neurology
Neurosciences
Oncology
Original Paper
oxidative stress
Oxidative Stress - drug effects
Oxidative Stress - physiology
Pyrrolidonecarboxylic Acid - metabolism
Pyrrolidonecarboxylic Acid - toxicity
Rats
Rats, Wistar
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Summary: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.
ISSN:0885-7490
1573-7365
DOI:10.1007/s11011-010-9190-1