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.