Oxidative stress has been proposed as an important pathophysiologic feature of various
inborn errors of metabolism, including
phenylketonuria (PKU). Considering that there are few studies relating oxidative stress and
inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules,
antioxidant defenses, pro-inflammatory
cytokines,
phenylalanine (Phe) and its metabolites (
phenyllactic acid--PLA and
phenylacetic acid--PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of
isoprostanes, which is a lipid peroxidation
biomarker, in urine from these treated patients. Next, we demonstrated that
protein oxidative damage, measured by di-
tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary
antioxidant capacity was also observed. Our findings concerning to the inflammatory
cytokines interleukin-6 and interleukin-1β, both significantly increased in these patients, provide evidence that the pro-inflammatory state occurs. Besides, interleukin-1β was positively correlated with
isoprostanes. We observed a negative correlation between
interleukin-6 and
interleukin-10, an anti-inflammatory
cytokine. Di-
tyrosine was positively correlated with Phe, which indicates oxidative damage to
proteins, as well as with PAA. These findings may suggest that the
protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that
pro-oxidant and pro-inflammatory states occur and are, in part, correlated and
protein oxidation seems to be induced by Phe and PPA in PKU patients.