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 (0.4mM phenylalanine concentration in the Dulbecco's Modified Eagle Medium (DMEM) solution), Phe addition to achieve 0.5, 1.0 or 1.5mM final phenylalanine concentrations. After 72h 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.