Medium-chain fatty acids accumulating in MCAD deficiency elicit lipid and protein oxidative damage and decrease non-enzymatic antioxidant defenses in rat brain.

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent disorder of fatty acid oxidation with a similar prevalence to that of phenylketonuria. Affected patients present tissue accumulation of the medium-chain fatty acids octanoate (OA), decanoate (DA) and cis-4-decenoate. Clinical presentation is characterized by neurological symptoms, such as convulsions and lethargy that may develop into coma and sudden death. The aim of the present work was to investigate the in vitro effect of OA and DA, the metabolites that predominantly accumulate in MCADD, on oxidative stress parameters in rat cerebral cortex homogenates. It was first verified that both DA and OA significantly increased chemiluminescence and thiobarbituric acid-reactive species levels (lipoperoxidation) and decreased the non-enzymatic antioxidant defenses, measured by the decreased total antioxidant capacity. DA also enhanced carbonyl content and oxidation of sulfhydryl groups (protein damage) and decreased reduced glutathione (GSH) levels. We also verified that DA-induced GSH decrease and sulfhydryl oxidation were not observed when cytosolic preparations (membrane-free supernatants) were used, suggesting a mitochondrial mechanism for these actions. Our present data show that the medium-chain fatty acids DA and OA that most accumulate in MCADD cause oxidative stress in rat brain. It is therefore presumed that this pathomechanism may be involved in the pathophysiology of the neurologic symptoms manifested by patients affected by MCADD.

• Authors: Patrícia F Schuck, Gustavo C Ferreira, Alana P Moura, Estela N B Busanello, Anelise M Tonin, Carlos S Dutra-Filho, Moacir Wajner
• Journal: Neurochemistry international (Neurochem Int) Vol. 54 Issue 8 Pg. 519-25 (Jul 2009) ISSN: 1872-9754 [Electronic] England
• PMID: 19428797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Fatty Acids
• Free Radicals
• Nerve Tissue Proteins
• Nitrates
• Nitrites
• Sulfhydryl Compounds
• Thiobarbituric Acid Reactive Substances
• Acyl-CoA Dehydrogenase
• Glutathione

Topics

• Acyl-CoA Dehydrogenase (deficiency)
• Animals
• Antioxidants (metabolism)
• Brain Chemistry (drug effects)
• Cerebral Cortex (drug effects, metabolism)
• Fatty Acids (metabolism)
• Free Radicals (metabolism)
• Glutathione (metabolism)
• Lipid Metabolism (physiology)
• Lipid Peroxidation (physiology)
• Luminescence
• Male
• Nerve Tissue Proteins (physiology)
• Nitrates (metabolism)
• Nitrites (metabolism)
• Oxidation-Reduction
• Oxidative Stress (physiology)
• Rats
• Rats, Wistar
• Sulfhydryl Compounds (metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)