Protective effects of S-nitrosoglutathione against neurotoxicity of 3-nitropropionic acid in rat

Mitochondrial dysfunction and oxidative stress are often linked to various neurodegenerative disorders including ischemic stroke and Huntington's disease (HD). S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier recently identified as a potent antioxidant capable of neutralizing oxidative stress. In the present study, we explore the neuroprotective effects of GSNO against metabolic insults induced by 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor commonly used as a pharmacological model for HD, in primary culture of fetal rat cortical and striatal neurons. Application of GSNO (1-5 microM) substantially reduced neuronal loss caused by 3-NP (1-5 mM) exposure based on MTT reduction, lactate dehydrogenase (LDH) release, and Hoechst staining assays. The protective effect of GSNO appeared to be more potent than N-acetyl-l-cysteine (NAC), a glutathione precursor, at the same concentrations. These results suggest that manipulation of GSNO metabolism may exert protective effects against mitochondrial dysfunction often observed in neurodegenerative disorders.