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.

Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model

“…Analogous, pyroglutamic acid (also known as 5-oxoproline), which was also identified as differentiating metabolites, is involved in glutamate availability for GSH synthesis and its accumulation induces oxidative stress [41]. Under hypoxic conditions, GSH synthesis is activated to compensate the high GSH consumption by the retina [42].…”

An in vitro approach to assess the neurotoxicity of valproic acid-induced oxidative stress in cerebellum and cerebral cortex of young rats

“…Free radical generation or oxidative stress develops when there is an imbalance between pro-oxidants and antioxidants ratio, leading to the generation of ROS. LPO is also one important cause of neuronal damage and the major consequence of enhanced LPO is attributed to the oxidative deterioration of the cellular membranes (Pederzolli et al, 2010). LPO produces major disturbances in cell function by damaging cellular macromolecules.…”

Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies

“…Accumulated 5-oxoproline is particularly harmful to the central nervous system [7]. Although the mechanism is not fully understood, 5-oxoproline accumulation appears to induce oxidative stress, which impairs energy metabolism in neural cells and is synergistic with excitotoxicity [14].…”