Phenylketonuria is the most frequent disturbance of
amino acid metabolism. Treatment for phenylketonuric patients consists of
phenylalanine intake restriction. However, there are patients who do not adhere to treatment and/or are not submitted to neonatal screening. These individuals are more prone to develop brain damage due to long-lasting toxic effects of high levels of
phenylalanine and/or its metabolites. Oxidative stress occurs in late-diagnosed phenylketonuric patients, probably contributing to the neurological damage in this disorder. In this work, we aimed to compare the influence of time exposition to high
phenylalanine levels on oxidative stress parameters in phenylketonuric patients who did not adhere to
protein restricted diet. We evaluated a large spectrum of oxidative stress parameters in plasma and erythrocytes from phenylketonuric patients with early and late diagnosis and of age-matched healthy controls. Erythrocyte
glutathione peroxidase activity and
glutathione levels, as well as plasma total
antioxidant reactivity were significantly reduced in both groups of patients when compared to the control group. Furthermore,
protein oxidative damage, measured by carbonyl formation and sulfhydryl oxidation, and lipid peroxidation, determined by
malondialdehyde levels, were significantly increased only in patients exposed for a long time to high
phenylalanine concentrations, compared to early diagnosed patients and controls. In conclusion, exposition to high
phenylalanine concentrations for a short or long time results in a reduction of non-enzymatic and enzymatic
antioxidant defenses, whereas
protein and
lipid oxidative damage only occurs in patients with late diagnosis.