Bezafibrate Prevents Glycine-Induced Increase of Antioxidant Enzyme Activities in Rat Striatum.

Abstract

Non-ketotic hyperglycinemia (NKH) is a severe neurological disorder caused by defects in glycine (GLY) catabolism and characterized by a high cerebrospinal fluid/plasma GLY ratio. Treatment is often ineffective and limited to the control of symptoms and detoxification of GLY. In the present work, we investigated the in vivo effects of GLY intracerebroventricular administration on oxidative stress parameters in rat striatum, cerebral cortex, and hippocampus. In vitro effects of GLY were also evaluated in striatum. The effects of bezafibrate (BEZ), a potential neuroprotective agent, on the possible alterations caused by GLY administration were further evaluated. Our in vivo results showed that GLY increased the activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH) in striatum. Furthermore, GLY decreased the concentrations of total glutathione and reduced glutathione (GSH), as well as GSH/oxidized glutathione ratio in vivo in hippocampus. In vitro data also showed that GLY induced lipid peroxidation and decreased GSH in striatum. Regarding the effects of BEZ, we found that GLY-induced increase of GPx, SOD, and GR activities was attenuated or prevented by this compound. However, BEZ did not alter GLY-induced decrease of GSH in hippocampus. We hypothesize that GLY-induced increase of the activities of antioxidant enzymes in striatum occurs as a mechanism to avoid accumulation of reactive oxygen species and consequent oxidative damage. Furthermore, since BEZ prevented GLY-induced alterations, it might be considered as an adjuvant therapy for NKH.

• Authors: Belisa Parmeggiani, Mateus Grings, Nevton Teixeira da Rosa-Junior, Renata Britto, Moacir Wajner, Guilhian Leipnitz
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 56 Issue 1 Pg. 29-38 (Jan 2019) ISSN: 1559-1182 [Electronic] United States
• PMID: 29675575 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Malondialdehyde
• Glutathione
• Glycine
• Bezafibrate

Topics

• Animals
• Antioxidants (metabolism)
• Bezafibrate (pharmacology)
• Corpus Striatum (drug effects, enzymology)
• Glutathione (metabolism)
• Glycine (administration & dosage, toxicity)
• Injections, Intraventricular
• Malondialdehyde (metabolism)
• Rats, Wistar