Nitric oxide (no) as a neuroprotective antioxidant in vivo

We have shown that NO is not toxic to brain neurons in vivo (Rauhala et al., Synapse, 1996). Based on antioxidant properties of NO (Rauhala et al., Free Radie. B/'oJ. Med., 1996), we propose that NO may protect cells and/or neurons against oxidative stress. In this study, we investigated possible neuroprotective effects of NO donor compounds against brain oxidative injury caused by intranigral infusion of ferrous citrate. Co-treatment of NO (-2 nmol in Ringer's solution) or NO donors such as S-nitrosoglutathione (GSNO; 2.1-16.8 nmol) and Snitroso-/V-acetylpenicillamine (4.2-8.4 nmol) suppressed acute lipid peroxidation in the rat substantia nigra caused by ferrous citrate (4.2 nmol, i.n.). S-Nitrosothiols also protected nigrostriatal dopamine neurons against iron-induced chronic striatal dopamine depletion. Freshly prepared GSNO, but not light exposed GSNO, inhibited iron-induced hydroxyl radicals generation, brain lipid peroxidation and oxidative stress. These in vivo results demonstrate that NO released from Snitrosothiols have antioxidative and neuroprotective properties that can against oxidative brain injury induced by hydroxyl radicals or small molecular weight iron complexes.