Francis-Turner, Liliana

The activities of the enzymes glutathione reductase (GRD), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were studied in several rat brain areas following the aspirative transection of the septohippocampal pathway (Fimbria fornix) and the administration of nerve growth factor (NGF) or cytochrome c. One group of animals remained untreated. This lesion resulted in a decreased hippocampal GRD and septal GST activities, as well as, in an increase in GPX activity from the frontal cortex, striatum, and septum. NGF prevented the lesion-induced changes in hippocampal GRD and septal GPX. These findings show that the insult resulting from the aspiration of the fimbria fornix bundle involves modifications in glutahione related enzymes, and therefore, in the antioxidant status of brain tissue. These changes in glutathione matabolism could be a consequence of the oxidative damage to GRD and GST proteins or represent a compensatory response of GPX to the oxidative threat. The restoring effects of NFG on altered enzyme activities are possibly linked to its known neuroprotective action.

Although the involvement of oxidative mechanisms in the cytotoxicity of excitatory amino acids has been well documented, it is not known whether the intrastriatal injection of quinolinic acid (QA) induces changes in glutathione (GSH) metabolism. In this work, the activities of the enzymes 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 intrastriatal injection of QA (225 nmol). One group of animals remained untreated. This lesion resulted in a 20% decrease in striatal GRD activity at both the 1- and 6-week postlesion times, whereas GST exhibited a 30% activity increase in the lesioned striatum observable only 6 weeks after the lesion. GPX activity remained unchanged. In addition, the QA injection elicited a 30% fall in GSH level at the 1-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 neutralize 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 glutathione metabolism.