The oxidative molecular regulation mechanism of NOX in children with phenylketonuria

Abstract

Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism. In our previous work, we investigated the role of NADPH oxidase (NOX) in a Pahenu2-BTBR PKU mouse model, and an in vitro cell culture model of PKU. In the current study, we evaluated various oxidative stress parameters, namely total antioxidant capacity (T-AOC), glutathione (GSH) and maleic dialdehyde (MDA) in the plasma of 40 PKU children, for further investigating the oxidative molecular regulation mechanism of NOX in PKU. It was observed that T-AOC and GSH markedly decreased in PKU as compared with the control group (P<0.01), and seemed to correlate negatively with Phe level. However, there was no statistical difference in MDA level among the three groups. And 8-isoprostane in the blood samples of PKU2 groups was slightly higher than control group (P<0.05). Additionally, mRNA levels of subunits of NOX included p47(phox) and p67(phox) significantly increased in PKU group (P<0.01). These results reflected that NOX is the important source of reactive oxygen species and is involved in the oxidative molecular regulation mechanism in PKU, which shows a new perspective toward understanding the biological underpinnings of PKU.

Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing

“…Changes in the microbiome associated with oxidative stress have been previously reported in animal models of chronic kidney disease [ 55 ]. Glutathione deficiency may provoke an imbalance between antioxidants and oxidants, generating oxidative stress, a situation that has been reported in patients with PKU [ 56 – 58 ]. While microbiome-associated changes in oxidative stress have already been described, the metabolic formula consumed by the PKU group contains antioxidants (vitamins A, C, D, E), suggesting that the microbiota might be modulated by the exogenous antioxidants provided by the formula.…”