2-Methylbutyrylglycine induces lipid oxidative damage and decreases the antioxidant defenses in rat brain.

Abstract

Short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency is an autosomal recessive disorder of isoleucine metabolism biochemically characterized by accumulation of 2-methylbutyrylglycine (2MBG) and 2-methylbutyric acid (2MB). Affected patients present predominantly neurological symptoms, whose pathophysiology is not yet established. In the present study, we investigated the in vitro effects of 2MBG and 2MB on important parameters of oxidative stress in cerebral cortex of young rats and C6 glioma cells. 2MBG increased thiobarbituric acid-reactive species (TBA-RS), indicating an increase of lipid oxidation. 2MBG induced sulfhydryl oxidation in cortical supernatants and decreased glutathione (GSH) in these brain preparations, as well as in C6 cells, indicating a reduction of nonenzymatic brain antioxidant defenses. In contrast, 2MB did not alter any of these parameters and 2MBG and 2MB did not affect carbonyl formation (protein damage). In addition, 2MBG-induced increase of TBA-RS levels and decrease of GSH were prevented by free radical scavengers, implying that reactive species were involved in these effects. Furthermore, the decrease of GSH levels caused by 2MBG was not due to a direct oxidative action since this metabolite did not alter sulfhydryl content from a commercial solution of GSH. Nitric oxide production was not altered by 2MBG and 2MB, suggesting that reactive oxygen species possibly underlie 2MBG effects. Finally, we verified that 2MBG did not induce cell death in C6 cells. The present data show that 2MBG induces lipid oxidative damage and reduces the antioxidant defenses in rat brain. Therefore, it may be postulated that oxidative stress induced by 2MBG is involved, at least in part, in the pathophysiology of the brain damage found in SBCAD deficiency.

• Authors: Lisiane Aurélio Knebel, Ângela Zanatta, Anelise Miotti Tonin, Mateus Grings, Leonardo de Moura Alvorcem, Moacir Wajner, Guilhian Leipnitz
• Journal: Brain research (Brain Res) Vol. 1478 Pg. 74-82 (Oct 10 2012) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 22967964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Butyrates
• Thiobarbituric Acid Reactive Substances
• 2-methylbutyrylglycine
• 2-methylbutanoic acid
• Glycine

Topics

• Amino Acid Metabolism, Inborn Errors (metabolism)
• Animals
• Antioxidants (metabolism)
• Butyrates (metabolism)
• Cerebral Cortex (metabolism)
• Glycine (analogs & derivatives, metabolism)
• Lipid Peroxidation (physiology)
• Male
• Oxidative Stress (physiology)
• Rats
• Rats, Wistar
• Thiobarbituric Acid Reactive Substances