Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats

Abstract

The aetiology of neuronal death in neurodegenerative diseases, including Huntington-s disease, is still unknown. There could be a complex interplay among altered energy metabolism, excitotoxicity and oxidative stress. Our aim was to examine the effects of intrastriatal injection of a selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, and a non-specific potent nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester, in order to study the possible involvement of glutathione, an important antioxidant, in quinolinic acid-induced striatal toxicity in the rat. Unilateral administration of quinolinic acid to rat striatum in a single dose of 150 nmol/L was used as a model of Huntington-s disease. The other group of animals were pretreated with 7- nitroindazole and Nw-nitro-L-arginine methyl ester, respectively. Control groups were treated with saline solution and olive oil, respectively. Content of total glutathione, was increased in the ipsi- and contralateral striatum, forebrain cortex, basal forebrain and hippocampus in the groups treated with nitric oxid synthase inhibitors and quinolinic acid compared to the quinolinic acid-treated animals. These results support the hypothesis that oxygen free radicals contribute to excitotoxic neuronal injury, and also that nitric oxide synthase inhibitors could be potential neuroprotective agents in Huntington-s disease.