Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria

Abstract

The aim of this study was to investigate the effects of phenylalanine on oxidative stress and some metabolic parameters in astrocyte cultures from newborn Wistar rats. Astrocytes were cultured under four conditions: control (0.4 mM phenylalanine concentration in the Dulbecco's Modified Eagle Medium (DMEM) solution), Phe addition to achieve 0.5, 1.0 or 1.5 mM final phenylalanine concentrations. After 72 h the astrocytes were separated for the biochemical measurements. Overall measure of mitochondrial function by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell viability measured by lactate dehydrogenase (LDH) assays indicated that phenylalanine induced cell damage at the three concentrations tested. The alteration on the various parameters of oxidative stress indicated that phenylalanine was able to induce free radicals production. Therefore, our results strongly suggest that Phe at concentrations usually found in PKU induces oxidative stress and consequently cell death in astrocytes cultures. Considering the importance of the astrocytes for brain function, it is possible that these astrocytes alterations may contribute to the brain damage found in PKU patients.

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria

“…We noted that 11 genes had a decreased expression significantly correlated with high plasma concentrations of Phe after multiple testing correction. These data support results of previous studies highlighting disturbance in redox system with reduction of total antioxidant status or unbalance of prooxidant-antioxidant system in blood samples of PKU patients (Sitta et al 2009;Sanayama et al 2011;Preissler et al 2016;Tavana et al 2016). Several plasma amino acids and urinary organic acids seem to be correlated with antioxidant expression profile.…”

Intermittent Fasting Enhanced the Cognitive Function in Older Adults with Mild Cognitive Impairment by Inducing Biochemical and Metabolic changes: A 3-Year Progressive Study

“…Although phenylalanine is crucial in the production of proteins or other molecules, the accumulation of phenylalanine can cause toxicity and damage to neuronal cells, which in turn disrupt the cognitive function [71]. High concentrations of phenylalanine in the cerebral cortex of mice have also been reported to induce the occurrence of oxidative stress and reduce the viability of astrocytes [72]. On the other hand, the glutathione metabolite pathway was found to be activated in the n-IF group.…”

Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters

“…Recently, Preissler et al [37] found that Phe increase oxidative stress and consequently cell death in astrocytes. They showed that pathological concentrations of Phe in PKU patients decrease astrocytes viability.…”