Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients

Abstract

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.

Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations

“…Deon et al observed high lipid and protein oxidative damage, decreased antioxidant defenses, and an increased infl ammatory status (IL-6 and IL-1β) in PKU patients (Deon et al, 2015). The discrepancy between Deon's and our results may result from diff erent characteristics of study group.…”

“…To the best knowledge of the authors, there was only one study focused on the infl ammatory status in PKU patients (Deon et al, 2015). It was focused on a group of patients diagnosed late in the course of the disease.…”

Oxidative damage in glutaric aciduria type I patients and the protective effects of l‐carnitine treatment

“…L-car deficiency is probably due to the fact that carnitine is used to promote the reduction of the excessive glutaryl coenzyme A toxic accumulation, releasing coenzyme A for other essential pathways. 34,35 In the current study, we demonstrated that GA-I patients present significantly increased urinary isoprostanes levels, a product of arachidonic acid metabolism and a biomarker of lipid peroxidation, as compared to the control group and that L-car treatment was able to normalize the isoprostane concentration indicating a prevention of lipid oxidation. Another important protective role of this highly polar quaternary amine was attributed to its antioxidant activity against free radicals, helping on the prevention to oxidative damage in various IEM.…”

Analysis of body composition and nutritional status in Brazilian phenylketonuria patients

“…In other pathologic conditions, ECM/BCM ratio has positively correlated with risk of death in dialysis patients [19] , while PA has been negatively affected by nutritional imbalances, thus used as a prognostic factor in patients with homocystinuria [20] and cancer [21] . Both ECM/BCM ratio and PA values have been related to increased inflammation [17] , [18] , [19] , [21] , which are seen in several pathological processes including in PKU patients [37] , [38] . Because nutritional imbalances have shown to underlie increased inflammation [23] , [24] , the Phe-restricted diet could represent a threat to the overall health of patients.…”