P 051 - Intracerebroventricular injection of glycine alters enzymatic antioxidant defenses in rat striatum: prevention by bezafibrate

Abstract

Non-ketotic hyperglycinemia (NKH) is an inborn error of metabolism caused by deficiency in the glycine (GLY) cleavage system and characterized by a high cerebrospinal fluid / plasma GLY ratio. NKH often results in early death, and therapeutical approaches are limited to controlling the symptoms, mainly seizures and hypotonia, and detoxifying GLY. Therefore, we evaluated antioxidant defenses in striatum, cerebral cortex and hippocampus of young rats following an intracerebral administration of GLY, as well as the beneficial effects of a pre-treatment with bezafibrate (BEZ), a potential neuroprotective compound, on the alterations caused by GLY. GLY administration increased the activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase in striatum, and decreased reduced glutathione concentrations in hippocampus. No significant alterations were verified in cerebral cortex. BEZ totally prevented GLY-induced increase of SOD and GR activities, and attenuated the increase of GPx activity. Our data show that GLY intracerebral administration disturbs antioxidant defenses in brain. In addition, since some alterations caused by GLY were prevented by BEZ, this compound may be considered as adjuvant therapy for NKH.