Effects of Nitric Oxide Synthase Inhibitors, 7-ni and L-name, on Content of Reduced Glutathione in Experimental Model Huntington′s Disease

The etiology of neuronal death in neurodegenerative diseases, including Huntington′s disease (HD), is still unknown. There could be a complex interplay between 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 nitro indazole (7-NI), and non-specific potent nitric oxide synthase inhibitor, Nω-nitro-l-arginine methyl ester (lNAME), to investigate the possible involvement of nitric oxide in quinolinic acid (QA)-induced striatal toxicity in the rat. Unilateral administration of QA in rat striatum in a single dose of 150 nM was used as model of HD. The second and third group were treated with 7-NI and QA and l-NAME and QA, respectively. The control group was treated with 0.9% saline solution likewise. The content of reduced glutathione, a key antioxidant, was increased in the hippocampus and basal forebrain of 7-NIand QA-treated animals, compared to the QA-treated animals. These results support the hypothesis that oxygen free radicals contribute to the excitotoxic neuronal injury, and also that neuronal nitric oxide synthase inhibitor 7-NI, but not l-NAME could be potential neuroprotective agents in HD.