Sodium Azide Induced Neuronal Damage In Vitro: Evidence for Non-Apoptotic Cell Death

• Published in: Neurochemical research Vol. 34; no. 5; pp. 909 - 916
• Main Authors: Selvatici, Rita, Previati, Maurizio, Marino, Silvia, Marani, Luca, Falzarano, Sofia, Lanzoni, Irene, Siniscalchi, Anna
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.05.2009; Springer Nature B.V
• Subjects: Acetylcarnitine - pharmacology; Animals; Antioxidants - pharmacology; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell death; Cell Death - drug effects; Cell Nucleus - drug effects; Cell Nucleus - ultrastructure; Cell Survival - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Chromans - pharmacology; Dizocilpine Maleate - pharmacology; Guanylate Cyclase - antagonists & inhibitors; Membrane Potential, Mitochondrial; Neurochemistry; Neurology; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Neuroprotective Agents - pharmacology; Neurosciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Original Paper; Oxadiazoles - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Sodium Azide - toxicity; Neuronal death; Mitochondrial failure; Cortical neurons; Sodium azide; Necrosis; Apoptosis
• DOI: 10.1007/s11064-008-9852-0
• ISSN: 0364-3190

The features of neuronal damage induced by the mitochondrial toxin NaN 3 were investigated in rat primary cortical neuron cultures. Cell viability (MTT colorimetric determination) and transmembrane mitochondrial potential (J-C1 fluorescence) were concentration-dependently reduced 24 h after NaN 3 ; neither nuclear fragmentation by DAPI, nor Annexin V positivity by flow cytometry were detected, ruling out the occurrence of apoptosis. The loss in cell viability (to 54 ± 2%) observed 24 h after a 10-min treatment with 3 mM NaN 3 was prevented by the NMDA glutamate receptor antagonist MK801 (1 μM), by the antioxidants trolox (100 μM) and acetyl- l -carnitine (1 mM) and by the nitric oxide synthase inhibitor, L-NAME (100 μM), but not by the guanylylcyclase inhibitor ODQ, 10 μM. The mitochondrial dysfunction induced by NaN 3 provides a common platform for investigating the mechanisms of both ischemic and degenerative neuronal injury, useful for screening potential protective agents against neuronal death.