Quinolinic acid lesion induces changes in rat striatal glutathione metabolism

ABSTRACT

Although the involvement of oxidative mechanisms in thecytotoxicity of excitatory amino acids has been well documented, it is not known whether the instrastriatal injection of quinolinic acid (QA) induces changes in gluthatione (GSH) metabolism. In this work, the activities of the enzynes GSH reductase (GRD), GSH peroxidase (GPX), and GSH S-transferase (GST), as well as the GSH content, were studied in the striatum, hippocampus, and frontal cortex of rats 1 and 6 weeks following the instrastriatal injection of QA (225 nmol). One group of animals remained untreated. This lesion resulted in a 20 porciento decrease in striatal GRD activity at both the 1- and 6-week postlesion time. GSH related enzyme activities and GSH content from other areas outside the lesioned striatum were not affected. GST activation could represent a beneficial compensatory response to neurtralize some of the oxidant agents generated by the lesion. However, this effect together with the reduction in GRD activity could be the cause or a contributing factor to the observed QA-induced deficit in GSH availability and, consequently, further disrupt the oxidant homeostasis of the injured striatal tissue. Therefore, these results provide evidence that the in vivo excitotoxic injury to the brain might affect oxidant/antioxidant equilibrium by eliciting changes in gluthatione metabolism(AU)