Acute Administration of 5-oxoproline Induces Oxidative Damage to Lipids and Proteins and Impairs Antioxidant Defenses in Cerebral Cortex and Cerebellum of Young Rats

Metab Brain Dis. 2010 Jun;25(2):145-54. doi: 10.1007/s11011-010-9190-1. Epub 2010 Apr 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Antioxidants / metabolism*
  • Antioxidants / physiology
  • 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
  • Lipid Peroxidation / drug effects*
  • Lipid Peroxidation / physiology
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Pyrrolidonecarboxylic Acid / metabolism
  • Pyrrolidonecarboxylic Acid / toxicity*
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Nerve Tissue Proteins
  • Glutathione Synthase
  • Pyrrolidonecarboxylic Acid