Quinolinic acid lesion induces changes in rat striatal glutathione metabolism.
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.
Cruz-Aguado
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International Center for Neurological Restoration, Neurochemistry Lab, Havana, Cuba. reyniel@neubas.sld.cu
Francis-Turner
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Díaz
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Antúnez
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D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D005978:Glutathione / Q000037:antagonists & inhibitors*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D008297:Male; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D017378:Quinolinic Acid; D005978:Glutathione