Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defenses in rat brain.

Abstract

AIMS:

We investigated the effects of in vivo intrastriatal administration of glycine (Gly), which is found at high concentrations in the brain of patients affected by nonketotic hyperglycinemia (NKH), on important parameters of oxidative stress.

MAIN METHODS:

Thiobarbituric acid-reactive substances values (TBA-RS, lipid peroxidation), carbonyl formation (protein oxidative damage), sulfhydryl content, reduced glutathione concentrations, nitric oxide production and the activities of the antioxidant enzymes glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and glucose-6-phosphate dehydrogenase (antioxidant defenses) were measured in striatum from 30-day-old rats after Gly injection.

KEY FINDINGS:

Gly administration significantly increased TBA-RS values, implying lipid oxidative damage. Furthermore, Gly-induced increase of TBA-RS was fully prevented by the NMDA receptor antagonist MK-801, indicating the involvement of the NMDA glutamate receptor in this effect. Gly injection also induced protein carbonyl formation, as well as elevation of the activities of glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase. In contrast, glutathione levels, sulfhydryl content, nitric oxide production and the activity of glucose-6-phosphate dehydrogenase were not modified by Gly.

SIGNIFICANCE:

The data shows that Gly in vivo administration causes lipid peroxidation, probably secondary to NMDA stimulation, induces protein oxidation and modulates the activities of important antioxidant enzymes in the striatum. In case these findings can be extrapolated to the human NKH, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this neurometabolic disease.

• Authors: Bianca Seminotti, Lisiane Aurélio Knebel, Carolina Gonçalves Fernandes, Alexandre Umpierrez Amaral, Mateus Struecker da Rosa, Paula Eichler, Guilhian Leipnitz, Moacir Wajner
• Journal: Life sciences (Life Sci) Vol. 89 Issue 7-8 Pg. 276-81 (Aug 15 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21762704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Glycine Agents
• Neuroprotective Agents
• Reactive Oxygen Species
• Thiobarbituric Acid Reactive Substances
• Dizocilpine Maleate
• Oxidoreductases
• Glycine

Topics

• Animals
• Brain (drug effects, metabolism)
• Corpus Striatum (drug effects, metabolism)
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Glycine (administration & dosage)
• Glycine Agents (administration & dosage)
• Hyperglycinemia, Nonketotic (metabolism, prevention & control)
• Lipid Peroxidation (drug effects)
• Microinjections
• Neuroprotective Agents (pharmacology)
• Oxidoreductases (metabolism)
• Protein Carbonylation (drug effects)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)